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Intracranial depth electrode EEG records of 478 seizures, recorded in 68 patients undergoing diagnostic monitoring with depth electrodes, were evaluated to investigate the correlates of electrographic onset patterns in patients with temporal lobe seizures. The seizure onsets in 78% of these patients were identified as either hypersynchronous onsets, beginning with low-frequency, high-amplitude spikes, or low-voltage fast (LVF) onsets, increasing in amplitude as the seizure progressed. The number of patients (35) having hypersynchronous seizure onsets was nearly twice that of patients (18) having LVF onsets. Three major differences were seen among patients with the two seizure-onset patterns. When compared with patients having LVF onsets, patients with hypersynchronous seizure onsets had a significantly greater probability of having (1) focal rather than regional seizure onsets (p < 0.01), (2) seizures spreading more slowly to the contralateral mesial temporal lobe (p < 0.003), and (3) cell counts in resected hippocampal tissue showing greater neuronal loss (p < 0.001). The results provide evidence that the most frequent electrographic abnormality associated with mesial temporal seizures is local hypersynchrony, a condition associated with major neuronal loss in the hippocampus. The results also indicate that LVF seizure onsets more frequently represent widely distributed discharges, which interact with and spread more rapidly to surrounding neocortical areas.

Abstract Background Caesarean section rates continue to increase worldwide with uncertain medical consequences. Auditing and analysing caesarean section rates and other perinatal outcomes in a reliable and continuous manner is critical for understanding reasons caesarean section changes over time. Methods We analyzed data on 97,095 women delivering in 120 facilities in 8 countries, collected as part of the 2004-2005 Global Survey on Maternal and Perinatal Health in Latin America. The objective of this analysis was to test if the "10-group" or "Robson" classification could help identify which groups of women are contributing most to the high caesarean section rates in Latin America, and if it could provide information useful for health care providers in monitoring and planning effective actions to reduce these rates. Results The overall rate of caesarean section was 35.4%. Women with single cephalic pregnancy at term without previous caesarean section who entered into labour spontaneously (groups 1 and 3) represented 60% of the total obstetric population. Although women with a term singleton cephalic pregnancy with a previous caesarean section (group 5) represented only 11.4% of the obstetric population, this group was the largest contributor to the overall caesarean section rate (26.7% of all the caesarean sections). The second and third largest contributors to the overall caesarean section rate were nulliparous women with single cephalic pregnancy at term either in spontaneous labour (group 1) or induced or delivered by caesarean section before labour (group 2), which were responsible for 18.3% and 15.3% of all caesarean deliveries, respectively. Conclusion The 10-group classification could be easily applied to a multicountry dataset without problems of inconsistencies or misclassification. Specific groups of women were clearly identified as the main contributors to the overall caesarean section rate. This classification could help health care providers to plan practical and effective actions targeting specific groups of women to improve maternal and perinatal care.

The aim of this study is to carry out a systematic review of the existing literature on postoperative morbidity after general anaesthesia (GA) in the dental care of paediatric patients, its frequency, characteristics and association with the intervention performed., Material and Methods: An exhaustive search of the literature published up to 23 February 2022 was carried out in PubMed, Web of Science, Cochrane and EBSCO, with the following strategy: (infant OR child OR adolescent) AND (Oral Surgical Procedures OR Dentistry, Operative) AND Anesthesia, General AND Postoperative Complications., Results: The most frequent reason for the indication of general anaesthesia was dental caries and its complications (up to 91.0% of patients), followed by lack of cooperation/anxiety and/or fear for dental procedures in the office (between 39.8 and 47.9%). There is a higher prevalence for treatments in the special patient group reaching 87.7% compared to 63.3% in healthy patients. The main comorbidities recorded were: physical or mental disability, neurological, haematological, cardiac disorders, asthma, Down's syndrome; it was not possible to establish their association with the intervention performed. Regarding complications, complaints occurred between 43.0 and 98.9% of cases within the first 24 hours, the main reason being pain (between 14.0% and 95.0%)., Conclusions: Pediatric dental procedures under GA carry a very low risk of major complications, but have a virtually universal incidence of minor complications., Competing Interests: Declaration of Competing Interest All authors have completed and submitted the Conflict of Interest Disclosure Form and none were reported., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Abstract: Previous studies have described synchronic electroencephalographic (EEG) patterns of the background activity that is characteristic of several vigilance states., Study Objectives: To explore whether the background synchronous activity of the amygdala-hippocampal-neocortical circuit is modified during sleep in the delta, theta, alpha, sigma, beta, and gamma bands characteristic of each sleep state., Methods: By simultaneously recording intracranial and noninvasive scalp EEG (10-20 system) in epileptic patients who were candidates for neurosurgery, we explored synchronous activity among the amygdala, hippocampus, and neocortex during wakefulness (W), Non-Rapid Eye Movement (NREM), and Rapid-Eye Movement (REM) sleep., Results: Our findings reveal that hippocampal-cortical synchrony in the sleep spindle frequencies was spread across the cortex and was higher during NREM versus W and REM, whereas the amygdala showed punctual higher synchronization with the temporal lobe. Contrary to expectations, delta synchrony between the amygdala and frontal lobe and between the hippocampus and temporal lobe was higher during REM than NREM. Gamma and alpha showed higher synchrony between limbic structures and the neocortex during wakefulness versus sleep, while synchrony among deep structures showed a mixed pattern. On the one hand, amygdala-hippocampal synchrony resembled cortical activity (i.e. higher gamma and alpha synchrony in W); on the other, it showed its own pattern in slow frequency oscillations., Conclusions: This is the first study to depict diverse patterns of synchronic interaction among the frequency bands during distinct vigilance states in a broad human brain circuit with direct anatomical and functional connections that play a crucial role in emotional processes and memory., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Resistance to antibiotics is a growing problem with repercussions on the choice of first-line treatment in urinary tract infection (UTI) in childhood., Objectives: To know the current pattern of antibiotic susceptibility/resistance of the most frequent germs that cause UTI in our healthcare area. Secondary objective is to know the evolution of these patterns over time., Patients and Methods: A cross-sectional retrospective study of UTI episodes in a first-level hospital in two periods: 1st January 2008-31th December 2010 and 1st January 2017-31th December 2019 through a review of medical records, recording the following variables: Age, sex, fever, hospital admission, uropathy/bladder dysfunction, antibiotic prophylaxis., Results: First period: 174 UTI episodes (156 patients); Second period: 266 UTI episodes (218 patients). The most frequently isolated germ was E. coli , but in patients with uropathy or bladder dysfunction, the percentage of different germs is greater. A significant increase in resistance to amoxicillin/clavulanate (from 12.2 to 24%) is observed between both periods, it remains stable and in an acceptable range for gentamicin, cotrimoxazole and slightly increases to first-generation cephalosporins. In patients with uropathy/bladder dysfunction, resistance to all these antibiotics is significantly increased., Conclusions: The increased resistance of the most frequent uropathogens in the UTI of the pediatric population of our healthcare area to amoxicillin/clavulanate makes it unsuitable as empirical therapy. First-generation cephalosporins are an adequate alternative in patients without risk factors.

A comparative analysis of the targets for deep brain stimulation (DBS) to treat refractory temporal lobe epilepsy and the rationale for its use is presented, with an emphasis on the latency to obtain the significant antiepileptic effect and the long-term seizure control. The analysis includes consideration of surgical techniques currently used to optimize antiseizure effects and decrease surgical risks. Seizure control is similar for programed DBS and DBS responsive to abnormal cortical or subcortical electroencephalogram (EEG) activity. There is no difference in the long-term seizure control between programmed and responsive and intermittent or continuous DBS. However, intermittent programed DBS may have a significant antiseizure effect starting in the first month when applied to a non-sclerotic tissue such as the parahippocampal cortex. DBS induces no neuropsychological deterioration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Velasco, Saucedo-Alvarado, Vazquez-Barron, Trejo and Velasco.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Objective: The authors sought to determine the antiseizure effects of deep brain stimulation (DBS) of the parahippocampal cortex (PHC) for treatment of drug-resistant mesial temporal lobe epilepsy (MTLE)., Methods: After a 3-month baseline period, 6 adult patients with drug-resistant MTLE and hippocampal sclerosis (HS) had stereoelectroencephalography (SEEG)-DBS electrodes implanted at the PHC for identification of the seizure onset zone (SOZ). Patients entered an 8-month, randomized, double-blind protocol for DBS, followed by a 12-month open-phase study. Monthly reports of seizure frequency were collected, with separate counting of focal seizures with or without awareness impairment (focal impaired awareness seizures [FIAS] or focal aware seizures [FAS], respectively) and focal evolving to bilateral generalized tonic clonic seizures (GTCS). Stimulation parameters were 130 Hz, 450 μsec, 2.5-3 V, and cyclic stimulation 1 minute on/4 minutes off., Results: The total seizure rate decrement during follow-up was 41% (CI 25%-56%), with better seizure control for GTCS (IQR 19%-20%) and FIAS (IQR 0%-16%), with FAS being less responsive (IQR 67%-236%). No neuropsychological deterioration was observed., Conclusions: PHC DBS induced important antiseizure effects in patients with incapacitating FIAS and GTCS, most likely through blocking the propagation of hippocampal-onset seizures. The PHC target can be easily and safely approached due to positioning away from vascular structures, and there was no evidence of DBS-induced cognitive deterioration.

Most public health measures to contain the COVID-19 pandemic are based on preventing the pathogen spread, and the use of oral antiseptics has been proposed as a strategy to reduce transmission risk. The aim of this manuscript is to test the efficacy of mouthwashes to reduce salivary viral load in vivo. This is a multi-centre, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of four mouthwashes (cetylpyridinium chloride, chlorhexidine, povidone-iodine and hydrogen peroxide) in SARS-CoV-2 salivary load measured by qPCR at baseline and 30, 60 and 120 min after the mouthrinse. A fifth group of patients used distilled water mouthrinse as a control. Eighty-four participants were recruited and divided into 12-15 per group. There were no statistically significant changes in salivary viral load after the use of the different mouthwashes. Although oral antiseptics have shown virucidal effects in vitro, our data show that salivary viral load in COVID-19 patients was not affected by the tested treatments. This could reflect that those mouthwashes are not effective in vivo, or that viral particles are not infective but viral RNA is still detected by PCR. Viral infectivity studies after the use of mouthwashes are therefore required. ( https://clinicaltrials.gov/ct2/show/NCT04707742 ; Identifier: NCT04707742)., (© 2021. The Author(s).)

The olfactory function shares the same cerebral structures as those involved in the origin and propagation of focal temporal lobe seizures. Likewise, functional magnetic resonance imaging (fMRI) allows the study of olfactory function. This suggests that by quantitatively studying the olfactory function with an olfactory paradigm through fMRI it is possible to identify the functional alteration produced by the epileptic focus. The objective of the present study was to assess the olfactory function in the side of the epileptic focus in patients with mesial temporal lobe epilepsy, using fMRI for smell, and propose a non-invasive diagnostic method for patients candidates to mesial temporal lobe epilepsy surgery., Methods: Patients (n = 18) with clinical diagnosis of mesial temporal lobe epilepsy, refractory to pharmacological treatment: 7 patients (38.9%) with non-invasive studies consistent enough to submit them to anterior temporal lobectomy, and 11 (61.1%) patients where focal onset seizures were identified by stereoelectroencephalography (SEEG) on the left temporal lobe in 5 (27.8%) and in both temporal lobes in 2 (11.1%). Patients were evaluated using EEG, MRI, neuropsychological data, and fMRI with olfactory paradigm. Results of the fMRI were compared with the laterality of the epileptic focus determined by intracranial electroencephalogram recordings through stereotactically placed electrodes, and with post-surgical outcome at one year of follow-up., Results: fMRI showed a lower olfactory activation in 81.8% concordant with unilateral onset seizures. There were significant differences of olfactory fMRI activation between epileptic and non-epileptic foci., Conclusion: Functional magnetic resonance imaging with an olfactory paradigm may be a non-invasive diagnostic tool to determine the laterality of seizure onset in the mesial temporal lobe., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Summary: In patients with mesial temporal lobe epilepsy, high-frequency, low-amplitude electrical stimulation (ES) was applied during 3 weeks through contacts of intracranial electrodes that defined the epileptogenic zone. This subacute ES induced cessation of spontaneous seizures, decreased the number of EEG interictal spikes, caused a 10-fold increase in threshold to induce postdischarges, and showed a profound decrease in regional blood flow of the stimulated area in SPECT studies. Autoradiography analysis of surgical specimens from these patients demonstrated increased expression of benzodiazepine receptors and in gamma-aminobutyric acid content, particularly in the parahippocampal cortex. These observations provided evidence of a gamma-aminobutyric acid-mediated antiepileptic effect induced by ES. Several reports of long-term hippocampal ES through internalized neurostimulators have confirmed the antiepileptic effect on mesial temporal lobe-initiated seizures, with preservation of neuropsychological performance, in particular memory functions. The experience of the authors is that the response is optimal in patients without hippocampal sclerosis evidenced by MRI, whereas it is less significant and delayed in patients with hippocampal sclerosis. Other studies reported the best result stimulating through the contacts in the subiculum, the transition between the hippocampus and parahippocampal cortex, that usually escapes to the hippocampal sclerosis. Currently, the effect of ES directed at the subiculum and the parahippocampal cortex in patients with hippocampal sclerosis is under investigation., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Summary: Centromedian thalamic nucleus is an intralaminar nucleus with vast connectivity to cerebral cortex and basal ganglia. It receives afferents from the brain stem through the central tegmental tract and is part of the diffuse thalamic projection system. Because the reticulothalamic system has been related to initiation and propagation of epileptic activity (centroencephalic theory of epilepsy), deep brain stimulation has been proposed to interfere with seizure genesis or propagation. Centromedian thalamic nucleus is a large nucleus laying nearby the anatomical references for stereotaxis and therefore a convenient surgical target to approach. Electrodes are implanted in the anterior ventral lateral part of the nucleus (parvocellular area), guided by intraoperative recruiting responses elicited by unilateral 6 to 8 Hz electrical stimulation delivered through the deep brain stimulation electrode. Therapeutic stimulation is delivered with the following parameters: 60 Hz, 450 μs, 3.0 V. Seizure control runs between 69% and 83% in different reports, decreasing mainly generalized seizures from the start, with significant improvement in neuropsychological performance. Significant decrease in seizure occurs from hours to days after the onset of deep brain stimulation. Some reports refer that seizure improvement may occur by the simple insertion of the deep brain stimulation electrodes, and therefore, it was used to treat refractory epileptic status., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Objective: To determine the usefulness and efficacy of radiofrequency ablations (RFA) of the Centromedian thalamic nucleus (CMN) to control primarily generalized or multifocal seizures in refractory epilepsy., Methods: Six patients with clinical diagnosis of multifocal or primarily generalized drug-resistant epilepsy were included. Bilateral RFA of the CMN was performed through a monopolar 1.8 mm. tip electrode with a temperature of 80 °C during 90 seconds. Patients were followed in every 3 months visit for 20 to 36 months and kept a monthly seizure count calendar. We also compared maximal paroxysmal electroencephalogram (EEG) activity and neuropsychological evaluation pre and 6 months postoperatively., Results: A significant reduction in the number of generalized seizures was observed in all subjects in the range of 79-98%, starting the first post-operative month. Although focal aware seizures remained unchanged throughout follow-up, there was an important reduction on paroxysmal activity between the pre and postoperative EEG. No major changes on cognitive status were detected. There was post-operative dysphagia and odynophagia lasting one week and there was no mortality in this group of patients., Conclusion: Preliminary results of CMN RFA suggest safety and a trend toward reduction of some seizure types, it may reduce the seizure frequency like other palliative procedures since the first post-operative month, but a larger, controlled study would be needed to establish the value of this therapy., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Evidence has been provided that the subiculum may play an important role in the generation of seizures. Electrical stimulation at this target has been reported to have anticonvulsive effects in kindling and pilocarpine rat models, while in a clinical study of hippocampal deep brain stimulation (DBS), contacts closest to the subiculum were associated with a better anticonvulsive effect., Objectives: To evaluate the effect of electrical stimulation of the subiculum in patients with refractory mesial temporal lobe epilepsy (MTLE) who have hippocampal sclerosis (HS)., Methods: Six patients with refractory MTLE and HS, who had focal impaired awareness seizures (FIAS) and focal to bilateral tonic-clonic seizures (FBTCS), had DBS electrodes implanted in the subiculum. During the first month after implantation, all patients were OFF stimulation, then they all completed an open-label follow-up of 24 months ON stimulation. DBS parameters were set at 3 V, 450 µs, 130 Hz, cycling stimulation 1 min ON, 4 min OFF., Results: There was a mean reduction of 49.16% (±SD 41.65) in total seizure number (FIAS + FBTCS) and a mean reduction of 67.93% (±SD 33.33) in FBTCS at 24 months. FBTCS decreased significantly with respect to baseline, starting from month 2 ON stimulation., Conclusions: Subiculum stimulation is effective for FBTCS reduction in patients with MTLE and HS, suggesting that the subiculum mediates the generalization rather than the genesis of mesial temporal lobe seizures. Better results are observed at longer follow-up times., (© 2020 S. Karger AG, Basel.)

Experimental evidence indicates that cannabidiol (CBD) induces anxiolytic and antiepileptic effects through the activation of 5-HT 1A receptors. These receptors are coupled to G i/o proteins and induce inhibitory effects. At present, the interaction of CBD with 5-HT 1A receptors in the human brain is unknown. The aim of this study focused on evaluating the interaction between CBD and 5-HT 1A receptors in cell membranes obtained from the hippocampus and temporal neocortex of autopsies and patients with drug-resistant mesial temporal lobe epilepsy (DR-MTLE). Cell membranes were isolated from the hippocampus and temporal neocortex of a group of patients with DR-MTLE who were submitted to epilepsy surgery ( n = 11) and from a group of autopsies ( n = 11). The [ 3 H]-8-OH-DPAT binding assay was used to determine the pharmacological interaction of CBD with 5-HT 1A receptors. The [ 35 S]-GTPγS assay was used to investigate the CBD-induced activation of G i/o proteins through its action on 5-HT 1A receptors.The CBD affinity (p K i ) for 5-HT 1A receptors was similar for autopsies and patients with DR-MTLE (hippocampus: 4.29 and 4.47, respectively; temporal neocortex: 4.67 and 4.74, respectively). Concerning the [ 35 S]-GTPγS assay, no statistically significant changes were observed for both hippocampal and neocortical tissue ( p > 0.05) at low CBD concentrations (1 pM to 10 μM). In contrast, at high concentrations (100 μM), CBD reduced the constitutive activity of G i/o proteins of autopsies and DR-MTLE patients (hippocampus: 39.2% and 39.6%, respectively; temporal neocortex: 35.2% and 24.4%, respectively). These changes were partially reversed in the presence of WAY-100635, an antagonist of 5-HT 1A receptors, in the autopsy group (hippocampus, 59.8%, p < 0.0001; temporal neocortex, 71.5%, p < 0.0001) and the group of patients with DR-MTLE (hippocampus, 53.7%, p < 0.0001; temporal neocortex, 68.5%, p < 0.001). Our results show that CBD interacts with human 5-HT 1A receptors of the hippocampus and temporal neocortex. At low concentrations, the effect of CBD upon G i/o protein activation is limited. However, at high concentrations, CBD acts as an inverse agonist of 5-HT 1A receptors. This effect could modify neuronal excitation and epileptic seizures in patients with DR-MTLE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Martínez-Aguirre, Carmona-Cruz, Velasco, Velasco, Aguado-Carrillo, Cuéllar-Herrera and Rocha.)

Purpose: The objectives of this study were to determine the inheritance pattern by which familial mesial temporal lobe epilepsy (FMTLE) is segregated in Mexican families, and to identify if there was an association between the clinical characteristics and the inheritance pattern., Method: We included a total of 25 families with two or more members affected with MTLE during two years and elaborated a family pedigree for each family. The inheritance pattern was classified as autosomal dominant (AD) or autosomal recessive (AR), considering the affected members. We used statistical analysis association and differences between clinical characteristics and inheritance patterns., Results: The affected families with the AD pattern were 15.7 fold times more likely to start seizures at 5 years of age or earlier than families with AR pattern, OR = 15.7 (IC 95% = 1.9-128.9). We observed a predominance and greater déjà vu association (64.4% vs 31.3%; p = 0.021), OR = 3.9 (CI 95% = 1.1-13.5) in patients with AD versus AR pattern. Finally, we identified that patients with AD pattern had a likelihood of presenting emotional alterations 5.6 times higher than AR (OR = 5.6, IC = 1.1-27.5)., Conclusion: FMTLE is a heterogeneous syndrome, both phenotypically and genotypically; thus, our findings may be helpful for clinical use to perform an early diagnosis, to provide timely treatment, and to prevent comorbidities associated to this disease. However, in order to identify the possible genetic causes underlying these inheritance patterns, the use of molecular studies is necessary., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of this research was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG., Methods: Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2'-[18F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BPND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ., Results: Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data., Conclusion: Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation., (© 2019 S. Karger AG, Basel.)

Objective: The aim of the present work was to characterize the dynamics of the human amygdala across the different sleep stages and during wakefulness., Methods: Simultaneous intracranial electrical recordings of the amygdala, hippocampus, and scalp electroencephalography during spontaneous sleep polysomnography in four patients suffering from epilepsy were analyzed., Results: Power spectrum of the amygdala revealed no differences between rapid eye movement (REM) and wakefulness for all frequencies except higher power at 9 Hz during wakefulness and some low Gamma frequencies. Conversely, higher power was observed in non-REM (NREM) sleep than wakefulness for Delta, Theta and Sigma., Conclusions: Our results showed similar activity in the amygdala between wakefulness and REM sleep suggesting that the amygdala is as active in REM as during wakefulness. The higher power in Sigma frequencies during NREM sleep suggests that amygdala slow activity may play a significant role during NREM in concurrence with hippocampal activity., Significance: While studies have described the metabolic activity of the human amygdala during sleep, our results show the corresponding electrical pattern during the whole night, pointing out an increase of slow activity during NREM sleep that might be subjected to similar influences as other subcortical brain structures, such as the hippocampus., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to evaluate the relation between cognitive performance and white matter (WM) integrity in patients with temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS)., Methods: We included 26 patients with TLE (10 right, 16 left onset) as well as 24 healthy controls matched for age, gender, and years of education. In addition to quantitative hippocampal volume and transverse relaxation (T2) evaluation, whole-brain WM was analyzed using fractional anisotropy (FA) maps, derived from the diffusion tensor model. Average FA values were obtained from 38 regions of interest (ROI) of the main WM fascicles using an atlas-based approach. All subjects underwent extensive coFignitive assessments, Wechsler Adult Intelligence Scale (WAIS-IV) and Wechsler Memory Scale (WMS-IV). Fractional anisotropy was correlated with neuropsychological scores, and group effects were evaluated. Finally, patients were clustered based on their cognitive performance to evaluate if clinical and structural variables relate to specific cognitive profiles., Results: Patients had differential alterations in the integrity of the WM dependent on seizure laterality and presence of hippocampal sclerosis. Patients with TLE showed, on average, lower scores in most of the cognitive assessments. Correlations between cognition and WM followed specific trajectories per group with TLE, particularly in Left-TLE, in which we found a marked association between cognitive abilities and WM abnormalities. Cluster analysis of cognitive performance revealed three cognitive profiles, which were associated with the degree and spread of WM abnormalities., Significance: White matter diffusion characteristics differ between patients, particularly in relation to seizure laterality and hippocampal damage. Moreover, WM abnormalities are associated with cognitive performance. The extent of WM alterations leads to disrupted cerebral intercommunication and therefore negatively affects cognition., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Selective improvement of symptoms may be required when treating Parkinson disease (PD) patients with a predominantly monosymptomatic clinical picture., Objective: To define a target in prelemniscal radiation fibers (Raprl) related to the physiopathology of tremor evidenced by tractography., Case Report: We report a patient with predominant unilateral rest and postural tremor, diagnosed as PD based on 80% improvement induced by the administration of L-DOPA/carbidopa, subsequently complicated by motor fluctuations, L-DOPA dyskinesia, and a reduced ON period. A stereotactic radiofrequency lesion was made for tremor control, and postoperative diffusion-weighted imaging (DWI) demonstrated the precise location and extension of the lesioned tract., Results: Perfect control of the tremor was achieved with the patient OFF medication; this has lasted for 5 years, without hypotonia in the treated extremities. DWI revealed a 3.0-mm lesion at the base of the nucleus ventralis intermedius (Vim) interrupting cerebellar-Vim fibers sparing the cerebellar ventralis oralis posterior nucleus component., Conclusion: Selective improvement of symptoms is feasible in patients with a predominantly monosymptomatic PD clinical presentation., (© 2018 S. Karger AG, Basel.)

The amygdaloid complex plays a crucial role in processing emotional signals and in the formation of emotional memories. Neuroimaging studies have shown human amygdala activation during rapid eye movement sleep (REM). Stereotactically implanted electrodes for presurgical evaluation in epileptic patients provide a unique opportunity to directly record amygdala activity. The present study analysed amygdala activity associated with REM sleep eye movements on the millisecond scale. We propose that phasic activation associated with rapid eye movements may provide the amygdala with endogenous excitation during REM sleep. Standard polysomnography and stereo-electroencephalograph (SEEG) were recorded simultaneously during spontaneous sleep in the left amygdala of four patients. Time-frequency analysis and absolute power of gamma activity were obtained for 250 ms time windows preceding and following eye movement onset in REM sleep, and in spontaneous waking eye movements in the dark. Absolute power of the 44-48 Hz band increased significantly during the 250 ms time window after REM sleep rapid eye movements onset, but not during waking eye movements. Transient activation of the amygdala provides physiological support for the proposed participation of the amygdala in emotional expression, in the emotional content of dreams and for the reactivation and consolidation of emotional memories during REM sleep, as well as for next-day emotional regulation, and its possible role in the bidirectional interaction between REM sleep and such sleep disorders as nightmares, anxiety and post-traumatic sleep disorder. These results provide unique, direct evidence of increased activation of the human amygdala time-locked to REM sleep rapid eye movements., (© 2016 European Sleep Research Society.)

Background: Prelemniscal radiations (Raprl) have been proposed as a target for the treatment of Parkinson's disease. We evaluated effectiveness of this target through UPDRS-III in patients treated with Raprl deep brain stimulation (Raprl-DBS) and followed from 24 to 48 months., Methods: Nineteen patients in Hoehn-Yahr stages II-III were implanted with tetrapolar deep brain stimulation electrodes in Raprl contralateral to the extremities with more prominent symptoms. Placement was assisted by MRI/CT/anatomical atlas fusion, microelectrode recording, and micro- and macro-stimulation. The effect on motor symptoms was evaluated in an open label protocol through specific items of the UPDRS-III score, applied pre-operatively and 6, 12, 24, and 48 months after the onset of stimulation in an OFF-medication/ON-stimulation condition. Changes in scores with regard to pre-operative condition were obtained for each symptom in both sides and statistical significance determined through double-tail Wilcoxon test. Influence of demographic variables on outcome was analyzed using linear regression testing., Results: A greater than 80% decrease in UPDRS score for contralateral symptoms (classified as excellent results) occurred in 14 patients (73.7%), while in the other 5 it decreased from 33 to 79% (considered suboptimal results). These changes remained statistically significant up to 48 months (p < 0.01), while ipsilateral symptoms progressively increased. Suboptimal results were associated with selective improvement of only one symptom., Conclusion: Raprl-DBS induces a long-term, significant improvement of contralateral acral symptoms of Parkinson's disease., (© 2016 International Neuromodulation Society.)

Experiments were designed to evaluate the tissue content of tele-methylhistamine (t-MeHA) and histamine as well as H3 receptor (H3 Rs) binding and activation of the heterotrimeric guanine nucleotide binding αi/o proteins (Gαi/o) coupled to these receptors in the hippocampus and temporal neocortex of patients (n = 10) with pharmacoresistant mesial temporal lobe epilepsy (MTLE). Patients with MTLE showed elevated tissue content of t-MeHA in the hippocampus. Analyses revealed that a younger age at seizure onset was correlated with a higher tissue content of t-MeHA, lower H3 R binding, and lower efficacy of Gαi/o protein activation in the hippocampus. We conclude that the hippocampus shows a reduction in the H3 R function associated with enhanced histamine. In contrast, the temporal neocortex displayed a high efficacy of H3 Rs Gαi/o protein activation that was associated with low tissue contents of histamine and t-MeHA. These results indicate an overactivation of H3 Rs leading to decreased histamine in the temporal neocortex. However, this situation was lessened in circumstances such as a longer duration of epilepsy or higher seizure frequency. It is concluded that decrease in H3 Rs function and enhanced levels of histamine may contribute to the epileptic activity in the hippocampus and temporal neocortex of patients with pharmacoresistant MTLE., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Objective: To better define prelemniscal radiations (Raprl) as a target for the control of tremor and rigidity in Parkinson's disease (PD)., Methods: A total of 36 deep brain stimulation (DBS) electrodes were stereotactically implanted in Raprl contralateral to the extremities to be treated. Effects on symptoms were evaluated using UPDRS-III before and after DBS, and significance was determined using the Wilcoxon test. The location of DBS contacts in cases with optimum versus suboptimum results was evaluated using Student's t test and percentage improvement correlated through a bivariable Pearson test. The power and percentage of spike components for microelectrode recordings were statistically compared between the target point and structures located above and below., Results: Raprl-DBS improved tremor and rigidity (p < 0.01). The potency of microelectrode recordings indicated that the target was formed by fibers. There was no correlation between demographic characteristics and clinical outcome, and there were no significant differences in stereotactic placement between cases with optimum and suboptimum results. Tremor and rigidity were selectively improved in cases with suboptimum results., Conclusion: Raprl-DBS is an effective treatment for the motor symptoms of PD. Selective improvement of symptoms suggests that the target has different fiber components related to either tremor or rigidity, and variations in improvement between cases may derive from individual variations of the location of these fibers.

The 5-hydroxytryptamine-1A (5-HT1A) receptors are known to be involved in the inhibition of seizures in epilepsy. Moreover, studies propose a role for the 5-HT1A receptor in memory function; it is believed that the higher density of this receptor in the hippocampus plays an important role in its regulation. Positron emission tomography (PET) studies in patients with mesial temporal lobe epilepsy (mTLE) have demonstrated that a decrease in 5-HT1A receptor binding in temporal regions may play a role in memory impairment. The evidences lead us to speculate whether this decrease in receptor binding is associated with a reduced receptor number or if the functionality of the 5-HT1A receptor-induced G-protein activation and/or the second messenger cascade is modified. The purpose of the present study is to determine 5-HT1A receptor-induced G-protein functional activation by 8-OH-DPAT-stimulated [(35)S]GTPγS binding assay in hippocampal tissue of surgical patients with mTLE. We correlate functional activity with epilepsy history and neuropsychological assessment of memory. We found that maximum functional activation stimulation values (Emax) of [(35)S]GTPγS binding were significantly increased in mTLE group when compared to autopsy samples. Furthermore, significant correlations were found: (1) positive coefficients between the Emax with the age of patient and frequency of seizures; (2) negative coefficients between the Emax and working memory, immediate recall and delayed recall memory tasks. Our data suggest that the epileptic hippocampus of patients with mTLE presents an increase in 5-HT1A receptor-induced G-protein functional activation, and that this altered activity is related to age and seizure frequency, as well as to memory consolidation deficit., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Neurostimulation enables adjustable and reversible modulation of disease symptoms, including those of epilepsy. Two types of brain neuromodulation, comprising anterior thalamic deep brain stimulation and responsive neurostimulation at seizure foci, are supported by Class I evidence of effectiveness, and many other sites in the brain have been targeted in small trials of neurostimulation therapy for seizures. Animal studies have mainly assisted in the identification of potential neurostimulation sites and parameters, but much of the clinical work is only loosely based on fundamental principles derived from the laboratory, and the mechanisms by which brain neurostimulation reduces seizures remain poorly understood. The benefits of stimulation tend to increase over time, with maximal effect seen typically 1-2 years after implantation. Typical reductions of seizure frequency are approximately 40% acutely, and 50-69% after several years. Seizure intensity might also be reduced. Complications from brain neurostimulation are mainly associated with the implantation procedure and hardware, including stimulation-related paraesthesias, stimulation-site infections, electrode mistargeting and, in some patients, triggered seizures or even status epilepticus. Further preclinical and clinical experience with brain stimulation surgery should lead to improved outcomes by increasing our understanding of the optimal surgical candidates, sites and parameters.

Mu opioid receptors (MOR) are known to be involved in seizure activity. The main goal of the present study was to characterize the MOR mRNA expression, binding, as well as G protein activation mediated by these receptors in epileptic hippocampus of patients with pharmacoresistant mesial temporal lobe epilepsy (TLE). In contrast with autopsy samples, hippocampus obtained from patients with mesial TLE demonstrated enhanced MOR mRNA expression (116%). Saturation binding experiments revealed significantly higher (60%) B(max) values for the mesial TLE group, whereas the K(d) values were not statistically different. Although mesial TLE group demonstrated high levels of basal binding for the G proteins (136%), DAMGO-stimulated [(35)S]GTPγS binding did not demonstrate significant alterations. In conclusion, our present data provide strong evidence that the epileptic hippocampus of patients with pharmacoresistant mesial TLE presents significant alterations in MOR. Such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations., (Copyright © 2010 Wiley Periodicals, Inc.)

Spastic diplegia is present in three-fourths of children with cerebral palsy, interfering with gait and frequently accompanied by severe pain. The authors report the case of a 28-year-old woman with history of perinatal hypoxia, who presented with cerebral palsy and severe spastic diplegia (Ashworth Scale Score 4, Tardieu Scale Score 5) and was confined to a wheelchair. She complained of pain in the left hip and knee with mixed neuropathic and somatic components. She consistently rated pain intensity as 10 of 10 on a visual analog scale, and her symptoms were resistant to multiple treatments. The patient underwent selective bilateral adductor myotomies and the implantation of an infusion pump for intrathecal lidocaine application. Postoperative control of pain and spasticity was dramatic (scores of 0 on the Ashworth, Tardieu, and visual analog scales) and persisted throughout a follow-up period of 36 months. This is the first report in the literature of combined selective neurotomies for the treatment of spasticity and chronic lidocaine subarachnoid infusion to treat associated pain. This therapy could represent an alternative to treat spasticity associated with neuropathic and somatic pain.

Motor cortex stimulation (MCS) is useful to treat patients with neuropathic pain syndromes, unresponsive to medical treatment. Complex regional pain syndrome (CRPS) is a segmentary disease treated successfully by spinal cord stimulation (SCS). However, CRPS often affects large body segments difficult to cover by SCS. This study analyzed the MCS efficacy in patients with CRPS affecting them. Five patients with CRPS of different etiologies underwent a small craniotomy for unilateral 20-grid-contact implantation on MC, guided by craniometric landmarks. Neurophysiological and clinical tests were performed to identify the contacts position and the best analgesic responses to MCS. The grid was replaced by a definitive 4-contacts-electrode connected to an internalized system. Pain was evaluated by international scales. Changes in sympathetic symptoms, including temperature, perspiration, color and swelling were evaluated. Pre-operative and post-operative monthly evaluations were performed during one year. A double-blind maneuver was introduced assigning two groups. One had stimulators turned OFF from day 30-60 and the other from day 60-90. Four patients showed important decrease in pain, sensory and sympathetic changes during the therapeutic trial, while one patient did not have any improvement and was rejected for implantation. VAS and McGill pain scales diminished significantly (p<0.01) throughout the follow-up, accompanied by disappearance of the sensory (allodynea and hyperalgesia) and sympathetic signs. MCS is effective not only to treat pain, but also improve the sympathetic changes in CPRS. Mechanism of action is actually unclear, but seems to involve sensory input at the level of the spinal cord.

Objective: Deep brain stimulation has been used in the treatment of refractory obsessive-compulsive disorder (OCD). Our principal objective was to determine the safety and effectiveness of deep brain stimulation of the inferior thalamic peduncle in the treatment of refractory OCD., Methods: An open protocol was performed from March 2003 to April 2007 in 5 patients with OCD refractory to conventional treatments. Bilateral stereotactic implantation of tetrapolar electrodes was aimed at the inferior thalamic peduncle and corroborated by electrophysiological responses and magnetic resonance imaging. All patients were off stimulation for 1 month after implantation. In the on-stimulation period, parameters were set at 5 V, 450 microseconds, 130 Hz in bipolar and continuous mode. Clinical changes were evaluated every 3 months for 12 months by means of the Yale-Brown Obsessive Compulsive Scale and the Global Assessment of Functioning scale. Statistical significance was assessed by the Friedman and Wilcoxon tests., Results: The mean Yale-Brown Obsessive Compulsive Scale score decreased from 35 to 17.8 (P < 0.001), and the mean Global Assessment of Functioning scale score improved from 20% to 70% (P < 0.0001). The neuropsychological battery did not show significant changes, and there were no side effects related to electrical stimulation in the chronic period., Conclusion: We conclude that inferior thalamic peduncle stimulation is a safe procedure and may be an effective alternative in the treatment of those OCD cases refractory to conventional treatments.

Background: Word reading involves several steps, from the visual perception of each of its constitutent elements to its recognition as an entity with a specific meaning. Various brain structures participate in these processes, depending of the linguistic and cognitive characteristics of the stimulus. Our objective was to characterize brain activity through the use of functional magnetic resonance imaging (FMRI) associated with the process of noun reading., Methods: Eleven healthy right-handed volunteers participated in a lexical decision task involving 58 written nouns. An equal number of letter sequences were used as control stimuli. Reaction times were also recorded., Results: There was a difference (p < 0.05) in reaction time between nouns and letter sequences in the lexical decision task. FMRI contrasted between conditions revealed significant activations in several areas involved in reading., Conclusions: The brain activation may reflect the different perceptual demands associated with the initial processing of nouns, as compared to meaningless letter sequences. We attribute the difference between our results and those previously reported to the particular characteristics of the pronunciation rules of written Spanish.

We report two cases of chronic therapeutic stimulation of epileptic foci localized in motor areas. Case 1 is an adolescent with supplementary motor area seizures whose intracranial recordings showed a right SMA focus. Case 2 is a female teenager with primary motor seizures originating in the right motor cortex in the hand area as shown by her intracranial recordings and cortical mapping. Both had apparently normal MRI. Chronic stimulation of the epileptic focus decreased the number of seizures more than 90% the seizure number while preserving motor function. None of the patients had side effects. Neuromodulation is proposed as a safe, efficient surgical alternative for motor seizure control.

Pilonidal disease and hidradenitis suppurativa are common problems that affect young adults. The surgical management of pilonidal disease should be tailored to the individual clinical presentation and its goal is the resolution of pilonidal disease with low recurrence and low morbidity. The clinical course of hidradenitis suppurativa is characterized by chronicity with frequent flare-ups followed by quiescent periods. Treatment for both conditions needs to be individualized to the clinical presentation.

We present here a review of the work on neuromodulation - defined as application of an inhibitory or excitatory current - on intracranial structures for the treatment of drug-resistant epilepsy. Near 250 patients were treated using a neuromodulation technique of the cerebellum (paravermian cortex), the CM-pf nucleus of the thalamus, the hippocampus, epileptogenic foci, and anterior ventral nucleus of the thalamus, with a one- to 15-year follow-up. Four contact strips were used for cerebellar and functional region neuromodulation, and DBS-type depth electrodes were stereotactically implanted for CM-pf and anterior nuclei of the thalamus and hippocampal neuromodulation. Electric stimulation was cyclic in almost all trials, using low frequency (10-40 Hz) for excitation and high frequency (60-185 Hz) for inhibition. Seizure frequency reduction was variable, depending on the neuromodulation site and patient selection, although seizure duration decreased in most patients. Cerebellar neuromodulation was followed by a 78% reduction in tonic and tonic-clonic seizures, CM-pf neuromodulation by an 83% reduction in tonic-clonic seizures and atypical absence of Lennox-Gastaut syndrome, with a 17.2% seizure-free and drug-free patient rate. Hippocampal neuromodulation was followed by a 73% reduction in partial complex seizures, with a 33% seizure-free patient rate. Anterior ventral nucleus of the thalamus was followed by a 63% reduction in tonic-clonic, tonic and atonic seizures. Several prognostic factors were identified in order to improve future results. There was no mortality and morbidity was limited to skin erosion at the neurostimulator site. Seizure reduction was associated with improved neuropsychological performance and better quality of life. Neuromodulation is safe and effective for the treatment of epileptic seizures of various origins. Several targets may be associated in a single patient, especially when bilateral hippocampal seizure foci are present.

Object: In this study the authors used a double-blind protocol to assess the efficacy of motor cortex stimulation (MCS) for treating neuropathic pain., Methods: Eleven patients with unilateral neuropathic pain (visual analog scale [VAS] score 8-10) of different origins and topography were selected for MCS. A 20-contact grid was implanted through a craniotomy centered over the motor cortex contralateral to the painful area. The motor cortex strip was identified using neuroimages, somatosensory evoked potentials, acute electrical stimulation, and corticocortical evoked potentials. Subacute therapeutic stimulation trials allowed the authors to determine the most efficient pair of contacts to use for long-term MCS. The grid was replaced with a 4-contact electrode connected to an internalized stimulator. Bipolar stimulation at a 40-Hz frequency, 90-micro sec pulse width, amplitude 2-7 V, and 1 hour in "ON" and 4 hours in "OFF" mode was used. Pain was evaluated using the VAS, Bourhis, and McGill pain scales applied each month for 1 year. At Day 60 or 90, the stimulators were turned to OFF mode for 30 days in a randomized, double-blind fashion. The statistical tool used was the Wilcoxon test., Results: Three patients did not report improvement in the subacute trial and were excluded from long-term MCS; the remaining patients underwent long-term stimulation. Significant improvement of pain was induced by MCS (p < 0.01); this persisted during the follow-up period. Turning stimulation to OFF mode increased pain significantly (p < 0.05). Improvement at 1 year was >or= 40% (40-86%) in all cases., Conclusions: Motor cortex stimulation is an efficient treatment for neuropathic pain, according to an evaluation facilitated by a double-blind maneuver. Subacute stimulation trials are recommended to determine the optimum motor cortex area to be stimulated and to identify nonresponders.

Objective: Tremor and rigidity have been efficiently controlled by electrical stimulation of contralateral prelemniscal radiations (Raprl) in patients with unilateral Parkinson's disease. The present study determines the effect of bilateral Raprl electrical stimulation in a group of patients with severe bilateral tremor, rigidity, and bradykinesia., Methods: Five patients with Parkinson's disease (Hoehn and Yahr scale, Stage V) underwent bilateral stereotactic electrode implantation. Postoperative magnetic resonance imaging studies confirmed their position. Bipolar chronic electrical stimulation was performed through contiguous contacts of each electrode, which were selected by means of a screening test that explored multiple combinations. Preoperative and 3-, 6-, 9-, and 12-month postoperative evaluations were performed using international rating scales. Postoperative evaluations were performed with 24 hours off medication-on stimulation., Results: Contralateral tremor and rigidity were significantly decreased by simple insertion of electrodes in Raprl and returned hours to days later. Contacts for chronic stimulation were located in the area between the red and subthalamic nuclei, including Raprl, zona incerta, and substantia Q. Efficient stimulation had at least one contact in Raprl and in four cases, both contacts were only in Raprl. Stimulation parameters were 90 to 130 Hz, 90 to 330 mus, and 1.5 to 3.5 V. Unified Parkinson's Disease Rating Scale (motor, Part III) scores decreased 65% (P < 0.001), with improvements of 90% in tremor (P < 0.001), 94% in rigidity (P < 0.001), 75% in bradykinesia (P < 0.001), 40% in gait, and 35% in postural stability (P < 0.05) at 1 year., Conclusion: Raprl electrical stimulation is safe and efficient to treat patients with the Parkinson's disease symptomatic triad. By use of Raprl stereotactic coordinates, electrodes were placed behind the subthalamic nucleus.

Opioid receptor binding was evaluated in parahippocampal cortex (PHC) obtained from patients with intractable mesial temporal lobe epilepsy (MTLE) with and without subacute high frequency electrical stimulation (HFS) in this brain area. Mu, delta and nociceptin receptor binding was determined by autoradiography in PHC of five patients (ESAE group) with MTLE history of 14.8 +/- 2.5 years and seizure frequency of 11 +/- 2.9 per month, two of them (40%) with mesial sclerosis. This group demonstrated antiepileptic effects following subacute HFS (130 Hz, 450 micros, 200-400 microA), applied continuously during 16-20 days in PHC. Values were compared with those obtained from patients with severe MTLE (history of 21.7 +/- 2.8 years and seizure frequency of 28.2 +/- 14 per month) in whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n = 4), patients with MTLE in whom no electrical stimulation was applied (MTLE group, n = 4) and autopsy material acquired from subjects without epilepsy (n = 4 obtained from three subjects). Enhanced 3H-DAMGO (MTLE, 755%; ESAE, 375%; ESWAE, 693%), 3H-DPDPE (MTLE, 242%; ESAE, 80%; ESWAE, 346%) and 3H-nociceptin (MTLE, 424%; ESAE, 217%; ESWAE, 451%) binding was detected in the PHC of all epileptic groups. However, tissue obtained from ESAE group demonstrated lower opioid receptor binding (3H-DAMGO, 44.5%, p < 0.05; 3H-DPDPE, 47%, p < 0.05; 3H-nociceptin, 39.3%, p < 0.5) when compared with MTLE group. The present results indicate that a high effectiveness to the antiepileptic effects induced by HFS is associated with reduced opioid peptide binding.