C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress.

The toxicity of misfolded proteins and mitochondrial dysfunction are pivotal factors that promote age-associated functional neuronal decline and neurodegenerative disease. Accordingly, neurons invest considerable cellular resources in chaperones, protein degradation, autophagy and mitophagy to maintain proteostasis and mitochondrial quality. Complicating the challenges of neuroprotection, misfolded human disease proteins and mitochondria can move into neighbouring cells via unknown mechanisms, which may promote pathological spread. Here we show that adult neurons from Caenorhabditis elegans extrude large (approximately 4 µm) membrane-surrounded vesicles called exophers that can contain protein aggregates and organelles. Inhibition of chaperone expression, autophagy or the proteasome, in addition to compromising mitochondrial quality, enhances the production of exophers. Proteotoxically stressed neurons that generate exophers subsequently function better than similarly stressed neurons that did not produce exophers. The extruded exopher transits through surrounding tissue in which some contents appear degraded, but some non-degradable materials can subsequently be found in more remote cells, suggesting secondary release. Our observations suggest that exopher-genesis is a potential response to rid cells of neurotoxic components when proteostasis and organelle function are challenged. We propose that exophers are components of a conserved mechanism that constitutes a fundamental, but formerly unrecognized, branch of neuronal proteostasis and mitochondrial quality control, which, when dysfunctional or diminished with age, might actively contribute to pathogenesis in human neurodegenerative disease and brain ageing.

The role of hybrid FDG-PET/MRI on decision-making in presurgical evaluation of drug-resistant epilepsy.

BACKGROUND: When MRI fails to detect a potentially epileptogenic lesion, the chance of a favorable outcome after epilepsy surgery becomes significantly lower (from 60 to 90% to 20-65%). Hybrid FDG-PET/MRI may provide additional information for identifying the epileptogenic zone. We aimed to investigate the possible effect of the introduction of hybrid FDG-PET/MRI into the algorithm of the decision-making in both lesional and non-lesional drug-resistant epileptic patients. METHODS: In a prospective study of patients suffering from drug-resistant focal epilepsy, 30 nonlesional and 30 lesional cases with discordant presurgical results were evaluated using hybrid FDG-PET/MRI. RESULTS: The hybrid imaging revealed morphological lesion in 18 patients and glucose hypometabolism in 29 patients within the nonlesional group. In the MRI positive group, 4 patients were found to be nonlesional, and in 9 patients at least one more epileptogenic lesion was discovered, while in another 17 cases the original lesion was confirmed by means of hybrid FDG-PET/MRI. As to the therapeutic decision-making, these results helped to indicate resective surgery instead of intracranial EEG (iEEG) monitoring in 2 cases, to avoid any further invasive diagnostic procedures in 7 patients, and to refer 21 patients for iEEG in the nonlesional group. Hybrid FDG-PET/MRI has also significantly changed the original therapeutic plans in the lesional group. Prior to the hybrid imaging, a resective surgery was considered in 3 patients, and iEEG was planned in 27 patients. However, 3 patients became eligible for resective surgery, 6 patients proved to be inoperable instead of iEEG, and 18 cases remained candidates for iEEG due to the hybrid FDG-PET/MRI. Two patients remained candidates for resective surgery and one patient became not eligible for any further invasive intervention. CONCLUSIONS: The results of hybrid FDG-PET/MRI significantly altered the original plans in 19 of 60 cases. The introduction of hybrid FDG-PET/MRI into the presurgical evaluation process had a potential modifying effect on clinical decision-making. TRIAL REGISTRATION: Trial registry: Scientific Research Ethics Committee of the Medical Research Council of Hungary. TRIAL REGISTRATION NUMBER: 008899/2016/OTIG . Date of registration: 08 February 2016.

Cost-effectiveness analysis of invasive EEG monitoring in drug-resistant epilepsy.

PURPOSE: Our aim was to determine the cost-effectiveness of two intracranial electroencephalography (iEEG) interventions: 1) stereoelectroencephalography (SEEG) and 2) placement of subdural grid electrodes (SDGs) both followed by resective surgery in patients with drug-resistant, partial-onset epilepsy, compared with medical management (MM) in Hungary from payer's perspective. METHODS: The incremental health gains and costs of iEEG interventions have been determined with a combination of a decision tree and prevalence Markov process model over a 30-year time horizon in a cost-utility analysis (CUA). To address the effect of parameter uncertainty on the incremental cost-effectiveness ratio (ICER), deterministic and probabilistic sensitivity analyses were performed. RESULTS: Our results showed that both SEEG and SDG interventions represent a more expensive but more effective strategy than MM representing the current standard of care. The total discounted cost of SEEG and SDG were € 32,760 and € 25,028 representing € 18,108 and € 10,375 additional cost compared with MM, respectively. However, they provide an additional 3.931 (in SEEG group) and 3.444 quality-adjusted life years (QALYs; in SDG group), correspondingly. Thus, the ICER of SEEG is € 4607 per QALY gain, while the ICER for SDG is € 3013 per QALY gain, compared with MM. At a cost-effectiveness threshold of € 41,058 per QALY in Hungary, both subtypes of iEEG interventions are cost-effective and provide good value for money. SIGNIFICANCE: Because of the high cost of implanting electrodes and monitoring, the invasive EEG for patients with refractory epilepsy is currently not available in the Hungarian national healthcare system. Our study demonstrated that these procedures in Hungary are cost-effective compared with the MM. As a result, the introduction of iEEG interventions to the reimbursement list of the National Health Insurance Fund Administration was initiated.

[Intracranial EEG monitoring methods]. / Intracranialis EEG-monitorozási eljárások.

Resective surgery is considered to be the best option towards achieving seizure-free state in drug-resistant epilepsy. Intracranial EEG (iEEG) is necessary if the seizure-onset zone is localized near to an eloquent cortical area, or if the results of presurgical examinations are discordant, or if an extratemporal epilepsy patient is MRI-negative. Nowadays, 3 kinds of electrodes are used: (1) foramen ovale (FO) electrodes; (2) subdural strip or grid electrodes (SDG); (3) deep electrodes (stereo-electroencephalographia, SEEG). The usage of FO electrode is limited to bitemporal cases. SDG and SEEG have a distinct philosophical approach, different advantages and disadvantages. SDG is appropriate for localizing seizure-onset zones on hemispherial or interhemispherial surfaces; it is preferable if the seizure-onset zone is near to an eloquent cortical area. SEEG is excellent in exploration of deeper cortical structures (depths of cortical sulci, amygdala, hippocampus), although a very precise planning is required because of the low spatial sampling. The chance for seizure-freedom is relatively high performing both methods (SDG: 55%, SEEG: 64%), beside a tolerable rate of complications.

Differences of brain electrical activity between moderate and severe obstructive sleep apneic patients: a LORETA study.

The effects of initiation of continuous positive airway pressure (CPAP) therapy on electroencephalographic (EEG) background activity were investigated in patients exhibiting both moderate (n = 13) and severe (n = 12) obstructive sleep apnea syndromes in the testing of the potential differences of alterations of brain electrical activity caused by chronic hypoxia between these two groups. A normal control group (n = 14) was also examined. Two EEG examinations were achieved in each group: before and after first-time CPAP therapy. Low-resolution electromagnetic tomography (LORETA) was implemented towards localizing the generators of EEG activity in separate frequency bands. Prior to CPAP treatment, as a common direction of change, analysis with LORETA demonstrated increased activity in comparison with the patient and control groups. In the moderate group, significant changes were detected in the alpha2 band in the posterior cingulate cortex as well as in the beta1 band in the right posterior parietal cortex and the left supramarginal gyrus. In the severe group, significant changes were found in theta and alpha1 bands in the posterior cingulate cortex. Following CPAP treatment, these significant differences vanished in the severe group. In the moderate group, significantly decreased activity was seen in the beta3 band in the right fusiform gyrus. These findings potentially suggest a normalizing effect of CPAP therapy on EEG background activity in both groups of obstructive sleep apnea syndrome patients. Compensatory alterations of brain electrical activity in regions associated with influencing successful memory retrieval, emotional perception, default mode network, anorexia and fear network caused by chronic intermittent hypoxia could possibly be reversed with the use of CPAP therapy.

Dynamic changes in sleep-related breathing abnormalities in bilateral paramedian mesencephalon and thalamus stroke: a follow-up case study.

BACKGROUND: Bilateral paramedian thalamic stroke is characterized by hypersomnia, vertical gaze palsy, amnestic alteration, and apathic state. Combined lesion of the paramedian thalamus and mesencephalon bilaterally is extremely rare. Little is known about the breathing disturbances of the particular region due to the lesion. The following describes the specific case of a woman, age 62, with bilateral paramedian thalamic and mesencephalic stroke. Initially, the patient's complaints exhibited altered vigilance and vertical gaze palsy. Notably, following the acute phase, fluctuating hypersomnia was detected. The MRI (brain) revealed an ischemic lesion in the medial part of the mesencephalon and paramedian thalamus, bilaterally. AIMS: The aim of the present study is to elucidate the involvement and characteristics of sleep-related breathing abnormalities in the clinical manifestation of the combined paramedian thalamic and mesencephalic stroke. METHODS: Polysomnographic recordings were accomplished seven times with 1-week interval between the consecutive recordings, toward investigating the early changes of sleep and sleep-related breathing abnormalities. RESULTS: Sleep structure examination featured a decrease in N3 and REM ratio and an increase in N1 and N2 ratio with minimal improvement during the recovery period. In contrast, significant changes were found in the breathing pattern: the initial central apnea dominance was followed by obstructive apneas with a gradual decrease of the total pathological respiratory events. CONCLUSION: In addition to the structural abnormality of the sleep regulating network, sleep-disordered breathing is another possible cause of hypersomnia in patients afflicted with the present localization of the lesion.

Impact of sand media continuous drying and rewetting cyclic on nutrients transformation performance from reclaimed wastewater effluent at soil aquifer treatment.

Reusing reclaimed wastewater became a practical resource for water utilization in groundwater recharge and irrigation activities. However, the quality of reclaimed wastewater needs improvement to meet the environmental regulations and reduce contamination risks. A laboratory-scale study simulated a soil aquifer treatment (SAT) system, exploring the synergistic effects of wet and dry cycles alongside key physicochemical parameters on pollutant removal efficiency using a glass column filled with quartz sand as the filtration medium. The investigation focused on the cyclic wetting and drying phases to unravel their impact on removing NH4+, NO3-, and PO43-. The synthetic wastewater introduced into the system exhibited varying pollutant concentrations during wet and dry periods, influenced by dynamic soil water content (WC%), pH, dissolved oxygen (DO), and oxidation-reduction potential (ORP). The high removal rates of 93% for PO43- and 43% for Total N2 demonstrate the system's capability to reduce concentrations significantly under dynamic alternating between wet and dry conditions. Results unveiled that the wet period consistently yielded higher removal rates for N2 species. Interestingly, for PO43-, the dry periods demonstrated a higher removal efficiency. Moreover, the study identified an average NO3- production during the experimental phases as a byproduct of nitrification. The average NO3- production in wet periods was 2.5 mg/L, whereas it slightly decreased to 2.2 mg/L in dry periods. These findings underscore the nuanced influence of wet and dry conditions on specific pollutants within SAT systems. Applying the logistic regression model and principal component analysis demonstrated the statistical significance of WC, pH, DO, and ORP in predicting wet/dry conditions, providing quantitative insights into their influential roles on the nutrient dynamic concentrations. This study contributes valuable data to our understanding of SAT systems, offering practical implications for designing and implementing sustainable wastewater treatment practices and pollution management across diverse environmental contexts.

Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system.

Caenorhabditis elegans is a powerful model for analysis of the conserved mechanisms that modulate healthy aging. In the aging nematode nervous system, neuronal death and/or detectable loss of processes are not readily apparent, but because dendrite restructuring and loss of synaptic integrity are hypothesized to contribute to human brain decline and dysfunction, we combined fluorescence microscopy and electron microscopy (EM) to screen at high resolution for nervous system changes. We report two major components of morphological change in the aging C. elegans nervous system: (1) accumulation of novel outgrowths from specific neurons, and (2) physical decline in synaptic integrity. Novel outgrowth phenotypes, including branching from the main dendrite or new growth from somata, appear at a high frequency in some aging neurons, but not all. Mitochondria are often associated with age-associated branch sites. Lowered insulin signaling confers some maintenance of ALM and PLM neuron structural integrity into old age, and both DAF-16/FOXO and heat shock factor transcription factor HSF-1 exert neuroprotective functions. hsf-1 can act cell autonomously in this capacity. EM evaluation in synapse-rich regions reveals a striking decline in synaptic vesicle numbers and a diminution of presynaptic density size. Interestingly, old animals that maintain locomotory prowess exhibit less synaptic decline than same-age decrepit animals, suggesting that synaptic integrity correlates with locomotory healthspan. Our data reveal similarities between the aging C. elegans nervous system and mammalian brain, suggesting conserved neuronal responses to age. Dissection of neuronal aging mechanisms in C. elegans may thus influence the development of brain healthspan-extending therapies.

[Antiepileptic drugs in treatment of epilepsy and follow up of their efficacy]. / Antiepileptikumok alkalmazása az epilepszia kezelésében és hatásosságuk követése.

Epilepsy is one of the most common neurological diseases usually demanding long term treatment. The prime goal of therapy is to achieve seizure freedom with avoidance of side effects. Precise diagnosis is fundamental selecting the proper antiepileptic drug(s). In addition of wide-spectrum antiepileptics, selective syndrome-specific antiepileptic drugs are available. Pharmacological features of the new antiepileptics allow more personalized clinical use. Aim of this paper is to provide a comprehensive pragmatic review of therapeutic possibilities and recommendations currently accessible in Hungary.

Effects of CPAP-therapy on brain electrical activity in obstructive sleep apneic patients: a combined EEG study using LORETA and Omega complexity : reversible alterations of brain activity in OSAS.

Effects of initiation of continuous positive airway pressure (CPAP) therapy on EEG background activity were investigated in patients with obstructive sleep apnea syndrome (OSAS, N = 25) to test possible reversibility of alterations of brain electrical activity caused by chronic hypoxia. Normal control group (N = 14) was also examined. Two EEG examinations were done in each groups: at night and in the next morning. Global and regional (left vs. right, anterior vs. posterior) measures of spatial complexity (Omega complexity) were used to characterize the degree of spatial synchrony of EEG. Low resolution electromagnetic tomography (LORETA) was used to localize generators of EEG activity in separate frequency bands. Before CPAP-treatment, a significantly lower Omega complexity was found globally and over the right hemisphere. Due to CPAP-treatment, these significant differences vanished. Significantly decreased Omega complexity was found in the anterior region after treatment. LORETA showed a decreased activity in all of the beta bands after therapy in the right hippocampus, premotor and temporo-parietal cortex, and bilaterally in the precuneus, paracentral and posterior cingulate cortex. No significant changes were seen in control group. Comparing controls and patients before sleep, an increased alpha2 band activity was seen bilaterally in the precuneus, paracentral and posterior cingulate cortex, while in the morning an increased beta3 band activity in the left precentral and bilateral premotor cortex and a decreased delta band activity in the right temporo-parietal cortex and insula were observed. These findings indicate that effect of sleep on EEG background activity is different in OSAS patients and normal controls. In OSAS patients, significant changes lead to a more normal EEG after a night under CPAP-treatment. Compensatory alterations of brain electrical activity in regions associated with influencing sympathetic outflow, visuospatial abilities, long-term memory and motor performances caused by chronic hypoxia could be reversed by CPAP-therapy.

PET/MRI in the Presurgical Evaluation of Patients with Epilepsy: A Concordance Analysis.

The aim of our prospective study was to evaluate the clinical impact of hybrid [18F]-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([18F]-FDG PET/MRI) on the decision workflow of epileptic patients with discordant electroclinical and MRI data. A novel mathematical model was introduced for a clinical concordance calculation supporting the classification of our patients by subgroups of clinical decisions. Fifty-nine epileptic patients with discordant clinical and diagnostic results or MRI negativity were included in this study. The diagnostic value of the PET/MRI was compared to other modalities of presurgical evaluation (e.g., electroclinical data, PET, and MRI). The results of the population-level statistical analysis of the introduced data fusion technique and concordance analysis demonstrated that this model could be the basis for the development of a more accurate clinical decision support parameter in the future. Therefore, making the establishment of "invasive" (operable and implantable) and "not eligible for any further invasive procedures" groups could be much more exact. Our results confirmed the relevance of PET/MRI with the diagnostic algorithm of presurgical evaluation. The introduction of a concordance analysis could be of high importance in clinical and surgical decision-making in the management of epileptic patients. Our study corroborated previous findings regarding the advantages of hybrid PET/MRI technology over MRI and electroclinical data.

Effect of Cannabidiol on the Long-Term Toxicity and Lifespan in the Preclinical Model Caenorhabditis elegans.

Introduction: Despite widespread use of cannabidiol (CBD), no lifelong toxicity study has been published to date. Caenorhabditis elegans is often used in preclinical lifelong toxicity studies, due to an estimated 60-80% of their genes having a human ortholog, and their short lifespan of ∼2-3 weeks. In this study, we examined both acute and long-term exposure studies of CBD at physiologically relevant concentrations. Materials and Methods: Acute toxicity was determined by treating day 1 adults with a wide range of CBD concentrations (0.4 µM to 4 mM) and assessing mortality and motility compared to control animals. Thermotolerance was examined by treating adult animals with CBD (0.4 µM to 4 mM) and exposing them to 37°C for 4 h, and then scoring for the number of alive animals treated with CBD compared to controls. Long-term toxicity was assessed by exposing day 1 adults to 10, 40, and 100 µM CBD until all animals perished. Control animals had no active drug exposure. Results: We report both acute and long-term exposure studies of CBD to adult C. elegans at physiologically relevant concentrations. Acute toxicity results showed that no animal died when exposed to 0.4-4000 µM CBD. The thermotolerance study showed that 40 µM CBD, but not other treatment levels, significantly increased resistance to heat stress by 141% compared to the untreated controls. Notably, whole-life exposure of C. elegans to 10-100 µM CBD revealed a maximum life extension of 18% observed at 40 µM CBD. In addition, motility analysis of the same groups revealed an increase in late-stage life activity by up to 206% compared to controls. Conclusion: These results serve as the only CBD lifelong exposure data in an in vivo model to date. While further research into the lifelong use of CBD should be carried out in mammalian models, the C. elegans model indicates a lack of long-term toxicity at physiologically relevant concentrations.

Inhibition of the neuromuscular acetylcholine receptor with atracurium activates FOXO/DAF-16-induced longevity.

Transcriptome-based drug screening is emerging as a powerful tool to identify geroprotective compounds to intervene in age-related disease. We hypothesized that, by mimicking the transcriptional signature of the highly conserved longevity intervention of FOXO3 (daf-16 in worms) overexpression, we could identify and repurpose compounds with similar downstream effects to increase longevity. Our in silico screen, utilizing the LINCS transcriptome database of genetic and compound interventions, identified several FDA-approved compounds that activate FOXO downstream targets in mammalian cells. These included the neuromuscular blocker atracurium, which also robustly extends both lifespan and healthspan in Caenorhabditis elegans. This longevity is dependent on both daf-16 signaling and inhibition of the neuromuscular acetylcholine receptor subunit unc-38. We found unc-38 RNAi to improve healthspan, lifespan, and stimulate DAF-16 nuclear localization, similar to atracurium treatment. Finally, using RNA-seq transcriptomics, we identify atracurium activation of DAF-16 downstream effectors. Together, these data demonstrate the capacity to mimic genetic lifespan interventions with drugs, and in doing so, reveal that the neuromuscular acetylcholine receptor regulates the highly conserved FOXO/DAF-16 longevity pathway.

Characteristic changes in brain electrical activity due to chronic hypoxia in patients with obstructive sleep apnea syndrome (OSAS): a combined EEG study using LORETA and omega complexity.

EEG background activity of patients with obstructive sleep apnea syndrome (OSAS, N = 25) was compared to that of normal controls (N = 14) to reflect alterations of brain electrical activity caused by chronic intermittent hypoxia in OSAS. Global and regional (left vs. right, anterior vs. posterior) measures of spatial complexity (Omega) were used to characterize the degree of spatial synchrony of EEG. Low resolution electromagnetic tomography (LORETA) was used to localize generators of EEG activity in separate frequency bands. Comparing patients to controls, lower Omega complexity was found globally and in the right hemisphere. Using LORETA, an increased medium frequency activity was seen bilaterally in the precuneus, paracentral and posterior cingulate cortex. These findings indicate that alterations caused by chronic hypoxia in brain electrical activity in regions associated with influencing emotional regulation, long-term memory and the default mode network. Global synchronization (lower Omega complexity) may indicate a significantly reduced number of relatively independent, parallel neural processes due to chronic global hypoxic state in apneic patients as well as over the right hemisphere.

[Postoperative outcome of surgical interventions for epilepsy between 2005 and 2016 at the Epilepsy Center of Pécs]. / Epilepsziasebészeti beavatkozások eredményei a Pécsi Epilepszia Centrumban 2005 és 2016 között.

INTRODUCTION: Epilepsy as a chronic, severe neurologic disease significantly influences the quality of life of the epileptic patients. In candidates well selected for surgery, the seizure freedom is realistically achievable, and the quality of life can be further improved with complex individual rehabilitation. AIM: We aimed to evaluate the postoperative outcome of patients who underwent epilepsy surgery between 2005 and 2016 at the Epilepsy Center at Pécs. METHOD: We evaluated seizure status at regular follow-up visits after surgery and the quality of life using questionnaires focusing on employment and social status. RESULTS: 76% of the 72 patients who underwent surgical resection for epilepsy were free from disabling seizures , and 10% had rare disabling seizures (almost seizure-free), 7% experienced worthwhile improvement and 7% had no worthwhile improvement. Comparing the employment status of patients free from disabling seizures to patients not free from disabling seizures, we found that the employment status is significantly influenced by seizure freedom (p<0.01, Fisher's exact test). While 67% of seizure-free patients were employed, only 19% of patients not free from disabling seizures were hired. CONCLUSION: Our results resemble the international tendencies and success rate, proving epilepsy surgery as an available, valid and effective treatment in well selected patients. Orv Hetil. 2019; 160(7): 270-278.

Surgical outcomes related to invasive EEG monitoring with subdural grids or depth electrodes in adults: A systematic review and meta-analysis.

PURPOSE: Resective epilepsy surgery based on an invasive EEG-monitors performed with subdural grids (SDG) or depth electrodes (stereo-electroencephalography, SEEG) is considered to be the best option towards achieving seizure-free state in drug-resistant epilepsy. The authors present a meta-analysis, due to the lack of such a study focusing on surgical outcomes originating from SDG- or SEEG-monitors. METHOD: English-language studies published until May 2018, highlighting surgical outcomes were reviewed. Outcome measures including total number of SDG- or SEEG-monitors and resective surgeries; consecutively followed surgical cases; surgical outcomes classified by Engel in overall, temporal/extratemporal and lesional/nonlesional subgroups were analyzed. RESULTS: 19 articles containing 1025 SDG-interventions and 16 publications comprising 974 SEEG-monitors were researched. The rate of resective surgery deriving from SDG-monitoring hovered at 88.8% (95%CI:83.3-92.6%) (I2 = 77.0%;p < 0.001); in SEEG-group, 79.0% (95%CI:70.4-85.7%) (I2 = 72.5%;p < 0.001) was measured. After SDG-interventions, percentage of post-resective follow-up escalated to 96.0% (95%CI:92.0-98.1%) (I2 = 49.1%;p = 0.010), and in SEEG-group, it reached 94.9% (95%CI:89.3-97.6%) (I2 = 80.2%;p < 0.001). In SDG-group, ratio of seizure-free outcomes reached 55.9% (95%CI:50.9-60.8%) (I2 = 54.47%;p = 0.002). Using SEEG-monitor, seizure-freedom occurred in 64.7% (95%CI:59.2-69.8%) (I2 = 11.9%;p = 0.32). Assessing lesional cases, likelihood of Engel I outcome was found in 57.3% (95%CI:48.7%-65.6%) (I2 = 69.9%;p < 0.001), using SDG; while in SEEG-group, it was 71.6% (95%CI:61.6%-79.9%) (I2 = 24.5%;p = 0.225). In temporal subgroup, ratio of seizure-freedom was found to be 56.7% (95%CI:51.5%-61.9%) (I2 = 3.2%;p = 0.412) in SDG-group; whereas, SEEG-group reached 73.9% (95%CI:64.4%-81.6%); (I2 = 0.00%;p = 0.45). Significant differences between seizure-free outcomes were found in overall (p = 0.02), lesional (p = 0.031), and also, temporal (p = 0.002) comparisons. CONCLUSIONS: SEEG-interventions were associated, at least, non-inferiorly, with seizure-freedom compared with SDG-monitors in temporal, lesional and overall subgroups.

Autophagy genes unc-51 and bec-1 are required for normal cell size in Caenorhabditis elegans.

Here we show that in the nematode Caenorhabditis elegans mutational inactivation of two autophagy genes unc-51/atg1 and bec-1/atg6/beclin1 results in small body size without affecting cell number. Furthermore, loss-of-function mutations in unc-51 and bec-1 suppress the giant phenotype of mutant animals with aberrant insulin-like growth factor-1 (insulin/IGF-1) or transforming growth factor-beta (TGF-beta) signaling. This function for unc-51 and bec-1 in cell size control and their interaction with these two growth modulatory pathways may represent a link between the hormonal and nutritional regulation of cell growth.

Imaging the cortical effect of lamotrigine in patients with idiopathic generalized epilepsy: a low-resolution electromagnetic tomography (LORETA) study.

PURPOSE: Anatomical localization of the cortical effect of lamotrigine (LTG) in patients with idiopathic generalized epilepsy (IGE). METHODS: 19 patients with untreated IGE were investigated. EEG was recorded in the untreated condition and 3 months later when LTG treatment abolished the seizures. 19-channel EEG was recorded, and a total of 2min artifact-free, waking EEG was processed to low-resolution electromagnetic tomography (LORETA) analysis. Activity (that is, current source density, A/m(2)) was computed in four frequency bands (delta, theta, alpha, and beta), for 2394 voxels that represented the cortical gray matter and the hippocampi. Group differences between the untreated and treated conditions were computed for the four bands and all voxels by multiple t-tests for interdependent datasets. The results were presented in terms of anatomical distribution and statistical significance. RESULTS: p<0.01 (uncorrected) changes (decrease of activity) emerged in the theta and the alpha bands. Theta activity decreased in a large cluster of voxels including parts of the temporal, parietal, occipital cortex bilaterally, and in the transverse temporal gyri, insula, hippocampus, and uncus on the right side. Alpha activity decreased in a relatively smaller cortical area involving the right temporo-parietal junction and surrounding parts of the cortex, and part of the insula on the right side. CONCLUSIONS: LTG decreased theta activity in several cortical areas where abnormally increased theta activity had been found in a prior study in another cohort of untreated IGE patients [Clemens, B., Bessenyei, M., Piros, P., Tóth, M., Seress, L., Kondákor, I., 2007b. Characteristic distribution of interictal brain electrical activity in idiopathic generalized epilepsy. Epilepsia 48, 941-949]. These LTG-related changes might be related to the decrease of seizure propensity in IGE.

Three-dimensional localization of abnormal EEG activity in migraine: a low resolution electromagnetic tomography (LORETA) study of migraine patients in the pain-free interval.

Investigating the brain of migraine patients in the pain-free interval may shed light on the basic cerebral abnormality of migraine, in other words, the liability of the brain to generate migraine attacks from time to time. Twenty unmedicated "migraine without aura" patients and a matched group of healthy controls were investigated in this explorative study. 19-channel EEG was recorded against the linked ears reference and was on-line digitized. 60 x 2-s epochs of eyes-closed, waking-relaxed activity were subjected to spectral analysis and a source localization method, low resolution electromagnetic tomography (LORETA). Absolute power was computed for 19 electrodes and four frequency bands (delta: 1.5-3.5 Hz, theta: 4.0-7.5 Hz, alpha: 8.0-12.5 Hz, beta: 13.0-25.0 Hz). LORETA "activity" (=current source density, ampers/meters squared) was computed for 2394 voxels and the above specified frequency bands. Group comparison was carried out for the specified quantitative EEG variables. Activity in the two groups was compared on a voxel-by-voxel basis for each frequency band. Statistically significant (uncorrected P < 0.01) group differences were projected to cortical anatomy. Spectral findings: there was a tendency for more alpha power in the migraine that in the control group in all but two (F4, C3) derivations. However, statistically significant (P < 0.01, Bonferroni-corrected) spectral difference was only found in the right occipital region. The main LORETA-finding was that voxels with P < 0.01 differences were crowded in anatomically contiguous cortical areas. Increased alpha activity was found in a cortical area including part of the precuneus, and the posterior part of the middle temporal gyrus in the right hemisphere. Decreased alpha activity was found bilaterally in medial parts of the frontal cortex including the anterior cingulate and the superior and medial frontal gyri. Neither spectral analysis, nor LORETA revealed statistically significant differences in the delta, theta, and beta bands. LORETA revealed the anatomical distribution of the cortical sources (generators) of the EEG abnormalities in migraine. The findings characterize the state of the cerebral cortex in the pain-free interval and might be suitable for planning forthcoming investigations.

Automatic recognition of anatomical regions in three-dimensional medical images.

This paper presents a method that detects anatomy regions in three-dimensional medical images. The method labels each axial slice of the image according to the anatomy region it belongs to. The detected regions are the head (and neck), the chest, the abdomen, the pelvis, and the legs. The proposed method consists of two main parts. The core of the algorithm is based on a two-dimensional feature extraction that is followed by a random forest classification. This recognition process achieves an overall accuracy of 91.5% in slice classification, but it cannot always provide fully consistent labeling. The subsequent post-processing step incorporates the expected sequence and size of the human anatomy regions in order to improve the accuracy of the labeling. In this part of the algorithm the detected anatomy regions (represented by Gaussian distributions) are fitted to the region probabilities provided by the random forest classifier. The proposed method was evaluated on a set of whole-body MR images. The results demonstrate that the accuracy of the labeling can be increased to 94.1% using the presented post-processing. In order to demonstrate the robustness of the proposed method it was applied to partial MRI scans of different sizes (cut from the whole-body examinations). According to the results the proposed method works reliably (91.3%) for partial body scans (having as little length as 35cm) as well.