Elevated ozone alters long-chain fatty acids in leaves of Japanese white birch saplings.

Long-chain fatty acids (LCFAs) in leaves have attracted attention as nutritious phytochemicals and olfactory signals that influence the behavior and growth of herbivorous insects. In recognition of the negative effects of increasing tropospheric ozone (O3) levels on plants, LCFAs can be altered through peroxidation by O3. However, how elevated O3 changes the amount and composition of LCFAs in field-grown plants is still unknown. We investigated palmitic, stearic, oleic, linoleic, linolenic LCFAs in the two leaf types (spring and summer) and two stages (early and late stage after expansion) of Japanese white birch (Betula platyphylla var. japonica) after a multi-year O3 exposure on the field. Summer leaves exhibited a distinct composition of LCFAs under elevated O3 at the early stage, whereas both stages of spring leaves did not exhibit significant changes in LCFAs composition by elevated O3. In the spring leaves, the amounts of saturated LCFAs significantly increased at the early stage, however, the amount of total, palmitic, and linoleic acids at the late stage were significantly decreased by elevated O3. Summer leaves had a lower amount of all LCFAs at both leaf stages. Regarding the early stage of summer leaves, the lower amount of LCFAs under elevated O3 was possibly due to O3-suppressed photosynthesis in the current spring leaves. Furthermore, the decrease ratio of spring leaves over time was significantly increased by elevated O3 in all LCFAs, whereas summer leaves did not exhibit such an effect. These findings suggest that further studies should be conducted to reveal the biological functions of LCFAs under elevated O3, considering the leaf type- and stage-dependent changes of LCFAs.

Ethylenediurea protects against ozone phytotoxicity not by adding nitrogen or controlling stomata in a stomata-unresponsive hybrid poplar.

Ozone (O3) pollution is a persistent environmental issue worldwide, which causes widespread damage to vegetation, deteriorating plant health and reducing plant productivity. Ethylenediurea (EDU) is a synthetic chemical that has been widely applied in scientific studies as a protectant against O3 phytotoxicities. Despite four decades of active research, the exact mechanisms to explain its mode of action remain unclear. Here, we aimed to reveal whether EDU's phytoprotective property is due to its control over stomatal regulation and/or its action as a nitrogen (N) fertilizer, utilizing stomatal-unresponsive plants of a hybrid poplar (Populus koreana × trichocarpa cv. Peace) grown in a free-air O3-concenctration enrichment (FACE) facility. Plants were treated with water (WAT), EDU (400 mg L-1), or EDU's constitutive amount of N every nine days, and exposed to ambient (AOZ) or elevated (EOZ) O3 during a growing season (June-September). EOZ led to extensive foliar injuries (but protected against rust disease), lower photosynthetic rate (A), impaired dynamics of responses of A to changes in light intensity, and smaller total plant leaf area. EDU protected against common phytotoxicities caused by EOZ without inducing stomatal closure, since stomatal conductance (gs) was generally unresponsive to the experimental treatments. EDU also modulated the dynamic response of A to light fluctuations under O3 stress. N addition acted as a fertilizer but did not satisfactorily protect plants against O3 phytotoxicities. The results suggest that EDU protects against O3 phytotoxicity not by adding N or controlling stomata, which provides a new insight into our understanding of the mode of action of EDU as a protectant against O3 phytotoxicity.

CDKL5 deficiency causes epileptic seizures independent of cellular mosaicism.

OBJECTIVE: In a study using a mouse model of CDKL5 deficiency disorder (CDD), seizures are specific to female mice heterozygous for Cdkl5 mutations and not observed in hemizygous knockout males or homozygous knockout females. The aim of this study was to examine whether the clinical phenotype of patients with CDD can be impacted by the type of genetic variant. METHODS: Eleven CDD patients (six females and five males) were included in this study. The molecular diagnosis of hemizygous male patients was performed using digital PCR and their clinical phenotypes were compared with those of patients with mosaic or heterozygous CDKL5 variants. The severity of clinical phenotypes was graded by using CDKL5 Developmental Score and the adapted version of the CDKL5 Clinical Severity Assessment. The effect of cellular mosaicism on the severity of CDD was studied by comparing the clinical characteristics and comorbidities between individuals with hemizygous and mosaic or heterozygous CDKL5 variants. RESULTS: One of the five male patients was mosaic for the CDKL5 variant. All patients developed seizures irrespective of their genetic status of the pathogenic variant. However, cellular mosaicism of CDKL5 deficiency was associated with lesser severity of other comorbidities such as feeding, respiratory, and visual functional impairments. SIGNIFICANCE: This study provided evidence that cellular mosaicism of CDKL5 deficiency was not necessarily required for developing epilepsy. CDD patients not only exhibited clinical features of epilepsy but also exhibited the developmental consequences arising directly from the effect of the CDKL5 pathogenic variant.

Biochar application improves karstic lime soil physicochemical properties and enzymes activity and enhances sweet tea seedlings physiological performance.

Karst lime soil, commonly found in rocky desert ecosystems of Southwest China, exhibits high pH, poor water retention, and intense erosion. To prevent further soil erosion and soil losses from these ecosystems, stabilization measures based on improved green infrastructure are needed. The present study aimed at elucidating the performance of sweet tea (Lithocarpus polystachyus) seedlings grown on this soil type upon biochar application. Biochar was classified into different particle sizes, viz. 0.25-0.5 mm (medium), 0.5-1 mm (coarse), 1-2 mm (gravel), and their mixture, and added at the concentrations of 1, 2, or 5% soil mass. The pH, moisture, and porosity of soil increased upon biochar application compared to control; however, soil bulk density significantly decreased. The activity of soil phosphatase was increased by biochar particle size. Biochar particle size and concentration significantly enhanced the soil organic carbon content, but they differently affected total and plant-available nutrients in the soil. Light-saturated photosynthesis was positively affected, while stomatal conductance, leaf transpiration, and the intercellular CO2 concentrations of sweet tea leaves were negatively affected by biochar particle size and/or concentration compared to control. Leaf chlorophyll and soluble protein contents were increased by biochar application. From these results, we conclude that biochar can improve soil properties and the performance of sweet tea seedlings grown on Karst lime soil. We suggest its application at a concentration of 2% soil mass for keeping a high physiological performance of sweet tea seedlings in this environment. The selection of the ideal particle size is context-specific and depends on the target outcome.

Big data-based urban greenness in Chinese megalopolises and possible contribution to air quality control.

Urban greenness is essential for people's daily lives, while its contribution to air quality control is unclear. In this study, Streetview big data of urban greenness and air quality data (Air Quality Index, PM2.5, PM10, SO2, NO2, O3, CO) from 206 monitoring stations from 27 provincial capital cities in China were analyzed. The national averages for the sky, ground and middle-level (shrub and short trees) view greenness were 5.4%, 5.5%, and 15.4%, respectively, and the sky:ground:middle ratio was 2:2:6. Street-view/bird-view greenness ratio averaged at 1.1. Large inter-city variations were observed in all the greenness parameters, and the weak associations between all street-view parameters and bird-eye greenspace percentage (21%-73%) indicate their representatives of different aspects of green infrastructures. All air quality parameters were higher in winter than in summer, except O3. Over 90% of air quality variation could be explained by socioeconomics and geoclimates, suggesting that air quality control in China should first reduce efflux from social economics, while geoclimatic-oriented ventilation facilitation design is also critical. For different air quality components, greenness had most significant associations with NO2, O3 and CO, and street-view/bird-view ratio was the most powerful indicator of all greenness parameters. Pooled-data analysis at national level showed that street-view greenness was responsible for 2.3% of the air quality variations in the summer and 3.6% in the winter; however, when separated into different regions (North-South China; East-West China), the explaining power increased up to 16.2%. Increased NO2 was accompanied with decreased O3, indicating NO titration effect. The higher O3 aligned with the higher street-view greenness, showing the greenness-related precursor risk for O3 pollution. Our study manifested that big internet data could identify the association of greenness and air pollution from street view scale, which can favor urban greenness management and evaluation in other regions where street-view data are available.

Hormesis induced by silver iodide, hydrocarbons, microplastics, pesticides, and pharmaceuticals: Implications for agroforestry ecosystems health.

Increasing amounts of silver iodide (AgI) in the environment are expected because of the recent massive expansion of weather modification programs. Concurrently, pharmaceuticals, microplastics, hydrocarbons, and pesticides in terrestrial ecosystems continue contaminating forests and agroforests. Our review supports that AgI induces hormesis, a biphasic dose response characterized by often beneficial low-dose responses and toxic high-dose effects, which adds to the evidence for pharmaceuticals, microplastics, hydrocarbons, and pesticides induced hormesis in numerous species. Doses smaller than the no-observed-adverse-effect-level (NOAEL) positively affect defense physiology, growth, biomass, yields, survival, lifespan, and reproduction. They also lead to negative or undesirable outcomes, including stimulation of pathogenic microbes, pest insects, and weeds with enhanced resistance to drugs and potential negative multi- or trans-generational effects. Such sub-NOAEL effects perplex terrestrial ecosystems managements and may compromise combating outbreaks of disease vectors that can threaten not only forest and agroforestry health but also sensitive human subpopulations living in remote forested areas.

Plant-insect communication in urban forests: Similarities of plant volatile compositions among tree species (host vs. non-host trees) for alder leaf beetle Agelastica coerulea.

Behavior of insects, such as pollination and grazing, is usually determined by biogenic volatile organic compounds (BVOCs). However, particularly in O3-polluted urban forests, the BVOCs-based plant-insect communication can be disrupted by the reaction of O3 with leaf-emitted BVOCs, such as between Japanese white birch (Betula platyphylla var. japonica) and a leaf beetle (Agelastica coerulea). To understand plant-insect communication in O3-polluted environments, it is necessary to identify chemical species of BVOCs that contribute to attractiveness toward insects but are diminished by elevated O3. In this study, we conducted olfactory response tests and gas chromatography mass spectrometry (GC-MS) analyses to clarify whether there is a similarity of BVOC components among Betulaceae host trees that can explain the attraction of the stenophagous insect A. coerulea. The olfactory response tests indicated that Betulaceae host trees attract A. coerulea via leaf-emitted BVOCs, while there was no preference of the leaf beetles to non-host trees (Sorbus commixta and Morus bombycis). However, GC-MS analyses indicated that the composition of BVOC blends considerably differed among Betulaceae host trees, although alders (Alnus hirsuta and A. japonica) had a similar composition of BVOC blend in each season (June and September) during which the adult leaf beetle is active. A distinct characteristic of the emission from B. platyphylla was that 2-carene and limonene, which are O3-reactive species, were emitted with a high monoterpene ratio irrespective of the season. Thus, these volatiles and the blend could be expected to lead the disrupted communication found between B. platyphylla and A. coerulea under elevated O3 in previous field studies. In addition, our results indicated that A. coerulea is attracted to more than one blend within Betulaceae host trees, suggesting that grazing damages can be affected by different host preferences and O3 reactivity with specific BVOCs in the field. BVOCs-based plant-insect interactions should be further studied in multi-species communities to better understand plant-insect communication in O3-polluted environments.

Monoallelic and bi-allelic variants in NCDN cause neurodevelopmental delay, intellectual disability, and epilepsy.

Neurochondrin (NCDN) is a cytoplasmatic neural protein of importance for neural growth, glutamate receptor (mGluR) signaling, and synaptic plasticity. Conditional loss of Ncdn in mice neural tissue causes depressive-like behaviors, impaired spatial learning, and epileptic seizures. We report on NCDN missense variants in six affected individuals with variable degrees of developmental delay, intellectual disability (ID), and seizures. Three siblings were found homozygous for a NCDN missense variant, whereas another three unrelated individuals carried different de novo missense variants in NCDN. We assayed the missense variants for their capability to rescue impaired neurite formation in human neuroblastoma (SH-SY5Y) cells depleted of NCDN. Overexpression of wild-type NCDN rescued the neurite-phenotype in contrast to expression of NCDN containing the variants of affected individuals. Two missense variants, associated with severe neurodevelopmental features and epilepsy, were unable to restore mGluR5-induced ERK phosphorylation. Electrophysiological analysis of SH-SY5Y cells depleted of NCDN exhibited altered membrane potential and impaired action potentials at repolarization, suggesting NCDN to be required for normal biophysical properties. Using available transcriptome data from human fetal cortex, we show that NCDN is highly expressed in maturing excitatory neurons. In combination, our data provide evidence that bi-allelic and de novo variants in NCDN cause a clinically variable form of neurodevelopmental delay and epilepsy, highlighting a critical role for NCDN in human brain development.

Ozone disrupts the communication between plants and insects in urban and suburban areas: an updated insight on plant volatiles.

Plant-insect interactions are basic components of biodiversity conservation. To attain the international Sustainable Development Goals (SDGs), the interactions in urban and in suburban systems should be better understood to maintain the health of green infrastructure. The role of ground-level ozone (O3) as an environmental stress disrupting interaction webs is presented. Ozone mixing ratios in suburbs are usually higher than in the center of cities and may reduce photosynthetic productivity at a relatively higher degree. Consequently, carbon-based defense capacities of plants may be suppressed by elevated O3 more in the suburbs. However, contrary to this expectation, grazing damages by leaf beetles have been severe in some urban centers in comparison with the suburbs. To explain differences in grazing damages between urban areas and suburbs, the disruption of atmospheric communication signals by elevated O3 via changes in plant-regulated biogenic volatile organic compounds and long-chain fatty acids are considered. The ecological roles of plant volatiles and the effects of O3 from both a chemical and a biological perspective are presented. Ozone-disrupted plant volatiles should be considered to explain herbivory phenomena in urban and suburban systems. Supplementary information: The online version of this article contains supplementary material available at (10.1007/s11676-020-01287-4) to authorized users.

Surgical strategy for refractory epilepsy secondary to porencephaly: ictal SPECT may obviate the need for intracranial electroencephalography. Patient series.

BACKGROUND: Surgical treatment of intractable epilepsy caused by porencephaly can be difficult because of poorly localizing or lateralizing electroclinical findings. The authors aimed to determine whether noninvasive evaluations are sufficient in these patients. OBSERVATIONS: Eleven patients were included in this study. The porencephalic cyst was in the left middle cerebral artery (MCA) area in 9 patients, the left posterior cerebral artery area in 1 patient, and the bilateral MCA area in 1 patient. Interictal electroencephalography (EEG) revealed multiregional, bilateral, interictal epileptiform discharges in 5 of 11 patients. In 6 of 10 patients whose seizures were recorded, the ictal EEG was nonlateralizing. Nine patients underwent ictal single-photon emission computed tomography (SPECT), which revealed lateralized hyperperfusion in 8 of 9 cases. Fluorodeoxyglucose positron emission tomography (FDG-PET) was useful for identifying the functional deficit zone. No patient had intracranial EEG. The procedure performed was hemispherotomy in 7 patients, posterior quadrant disconnection in 3 patients, and occipital disconnection in 1 patient. A favorable seizure outcome was achieved in 10 of 11 patients without the onset of new neurological deficits. LESSONS: Ictal SPECT was useful for confirming the side of seizure origin when electroclinical findings were inconclusive. Thorough noninvasive evaluations, including FDG-PET and ictal SPECT, enabled curative surgery without intracranial EEG. Seizure and functional outcomes were favorable.

Ethylenediurea (EDU) effects on Japanese larch: an one growing season experiment with simulated regenerating communities and a four growing season application to individual saplings.

Japanese larch (Larix kaempferi (Lamb.) Carr.) and its hybrid are economically important coniferous trees widely grown in the Northern Hemisphere. Ground-level ozone (O3) concentrations have increased since the pre-industrial era, and research projects showed that Japanese larch is susceptible to elevated O3 exposures. Therefore, methodologies are needed to (1) protect Japanese larch against O3 damage and (2) conduct biomonitoring of O3 in Japanese larch forests and, thus, monitor O3 risks to Japanese larch. For the first time, this study evaluates whether the synthetic chemical ethylenediurea (EDU) can protect Japanese larch against O3 damage, in two independent experiments. In the first experiment, seedling communities, simulating natural regeneration, were treated with EDU (0, 100, 200, and 400 mg L-1) and exposed to either ambient or elevated O3 in a growing season. In the second experiment, individually-grown saplings were treated with EDU (0, 200 and 400 mg L-1) and exposed to ambient O3 in two growing seasons and to elevated O3 in the succeeding two growing seasons. The two experiments revealed that EDU concentrations of 200-400 mg L-1 could protect Japanese larch seedling communities and individual saplings against O3-induced inhibition of growth and productivity. However, EDU concentrations ≤ 200 mg L-1 did offer only partial protection when seedling communities were coping with higher level of O3-induced stress, and only 400 mg EDU L-1 fully protected communities under higher stress. Therefore, we conclude that among the concentrations tested the concentration offering maximum protection to Japanese larch plants under high competition and O3-induced stress is that of 400 mg EDU L-1. The results of this study can provide a valuable resource of information for applied forestry in an O3-polluted world.

Efficient detection of copy-number variations using exome data: Batch- and sex-based analyses.

Many algorithms to detect copy number variations (CNVs) using exome sequencing (ES) data have been reported and evaluated on their sensitivity and specificity, reproducibility, and precision. However, operational optimization of such algorithms for a better performance has not been fully addressed. ES of 1199 samples including 763 patients with different disease profiles was performed. ES data were analyzed to detect CNVs by both the eXome Hidden Markov Model (XHMM) and modified Nord's method. To efficiently detect rare CNVs, we aimed to decrease sequencing biases by analyzing, at the same time, the data of all unrelated samples sequenced in the same flow cell as a batch, and to eliminate sex effects of X-linked CNVs by analyzing female and male sequences separately. We also applied several filtering steps for more efficient CNV selection. The average number of CNVs detected in one sample was <5. This optimization together with targeted CNV analysis by Nord's method identified pathogenic/likely pathogenic CNVs in 34 patients (4.5%, 34/763). In particular, among 142 patients with epilepsy, the current protocol detected clinically relevant CNVs in 19 (13.4%) patients, whereas the previous protocol identified them in only 14 (9.9%) patients. Thus, this batch-based XHMM analysis efficiently selected rare pathogenic CNVs in genetic diseases.

Characteristics of internalization of NMDA-type GluRs with antibodies to GluN1 and GluN2B.

To characterize internalization of NMDA-type glutamate receptors (GluRs) by antibodies to NMDA-type GluRs, we produced rabbit antibodies to N-terminals of human GluN1 and GluN2B, and examined internalization of NMDA-type GluRs in HEK293T cells using confocal microscopy. Internalization of NMDA-type GluRs occurred from at least 10 min after incubation with antibodies to GluN1 and or GluN2B and was temperature-dependent. These findings confirm that antibodies to N-terminals of GluN1 and GluN2B present in the cerebrospinal fluid of patients with NMDAR encephalitis can mediate prompt internalization of NMDA-type GluR complexes.

Heterophyllous Shoots of Japanese Larch Trees: The Seasonal and Yearly Variation in CO2 Assimilation Capacity of the Canopy Top with Changing Environment.

Japanese larch (Larix kaempferi = L. leptolepis) is often characterized by its high growth rate with heterophyllous shoots, but the functional differences of heterophyllous shoots still remain unclear. Recently, abrupt high temperature and drought during spring induced high photosynthetic rate via change in leaf morphology of the deciduous habit. In order to reveal the photosynthetic characteristics of both short and long-shoot needles of sunny canopy of the larch trees using a canopy tower, we calculated the seasonal change of gas exchange characters and leaf mass per area (LMA) and foliar nitrogen content (N) of heterophyllous needles: short and long-shoot needles over 3 years. No marked difference in light-saturated photosynthetic rates (Psat) was observed between short and long shoots after leaf maturation to yellowing, although the difference was obvious in a specific year, which only shows that seasonal change in temperature and soil moisture determines the in situ photosynthetic capacity of needles. The large annual and seasonal variations in Psat in both shoots were found to be mainly determined by climatic variations, while shoot types determined the strategy of their photosynthetic N utilization as well as the stomatal regulation.

Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6-dependent Epilepsy Than Pyridoxal 5'-Phosphate.

BACKGROUND: We aimed to demonstrate the biochemical characteristics of vitamin B6-dependent epilepsy, with a particular focus on pyridoxal 5'-phosphate and pyridoxal in the cerebrospinal fluid. METHODS: Using our laboratory database, we identified patients with vitamin B6-dependent epilepsy and extracted their data on the concentrations of pyridoxal 5'-phosphate, pyridoxal, pipecolic acid, α-aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low pyridoxal 5'-phosphate concentrations. RESULTS: We identified seven patients with pyridoxine-dependent epilepsy caused by an ALDH7A1 gene abnormality, two patients with pyridoxal 5'-phosphate homeostasis protein deficiency, and 28 patients with other epilepsies with low cerebrospinal fluid pyridoxal 5'-phosphate concentrations. Cerebrospinal fluid pyridoxal and pyridoxal 5'-phosphate concentrations were low in patients with vitamin B6-dependent epilepsy but cerebrospinal fluid pyridoxal concentrations were not reduced in most patients with other epilepsies with low cerebrospinal fluid pyridoxal 5'-phosphate concentrations. Increase in 3-O-methyldopa and 5-hydroxytryptophan was demonstrated in some patients with vitamin B6-dependent epilepsy, suggestive of pyridoxal 5'-phosphate deficiency in the brain. CONCLUSIONS: Low cerebrospinal fluid pyridoxal concentrations may be a better indicator of pyridoxal 5'-phosphate deficiency in the brain in vitamin B6-dependent epilepsy than low cerebrospinal fluid pyridoxal 5'-phosphate concentrations. This finding is especially helpful in individuals with suspected pyridoxal 5'-phosphate homeostasis protein deficiency, which does not have known biomarkers.

Interactive effect of leaf age and ozone on mesophyll conductance in Siebold's beech.

Mesophyll conductance (Gm ) is one of the most important factors determining photosynthesis. Tropospheric ozone (O3 ) is known to accelerate leaf senescence and causes a decline of photosynthetic activity in leaves. However, the effects of age-related variation of O3 on Gm have not been well investigated, and we, therefore, analysed leaf gas exchange data in a free-air O3 exposure experiment on Siebold's beech with two levels (ambient and elevated O3 : 28 and 62 nmol mol-1 as daylight average, respectively). In addition, we examined whether O3 -induced changes on leaf morphology (leaf mass per area, leaf density and leaf thickness) may affect CO2 diffusion inside leaves. We found that O3 damaged the photosynthetic biochemistry progressively during the growing season. The Gm was associated with a reduced photosynthesis in O3 -fumigated Siebold's beech in August. The O3 -induced reduction of Gm was negatively correlated with leaf density, which was increased by elevated O3 , suggesting that the reduction of Gm was accompanied by changes in the physical structure of mesophyll cells. On the other hand, in October, the O3 -induced decrease of Gm was diminished because Gm decreased due to leaf senescence regardless of O3 treatment. The reduction of photosynthesis in senescent leaves after O3 exposure was mainly due to a decrease of maximum carboxylation rate (Vcmax ) and/or maximum electron transport rate (Jmax ) rather than diffusive limitations to CO2 transport such as Gm . A leaf age×O3 interaction of photosynthetic response will be a key for modelling photosynthesis in O3 -polluted environments.

Methylprednisolone pulse therapy in 31 patients with refractory epilepsy: A single-center retrospective analysis.

PURPOSE: We investigated the efficacy of methylprednisolone pulse therapy (MP) and responder characteristics in patients with refractory epilepsy. METHODS: We reviewed medical records of our center to identify patients with refractory epilepsy treated with MP other than continuous spikes and waves during slow sleep (CSWS), Landau-Kleffner syndrome (LKS), or Rasmussen's syndrome (RS) between 2004 and 2015. A course of MP consisted of intravenous methylprednisolone (30 mg/kg/day) on three consecutive days. Patients received multiple courses at intervals of four weeks. We examined seizure outcome, developmental outcome, antibodies to N-methyl-d-aspartate (NMDA)-type glutamate receptors (GluRs), cerebral spinal fluid (CSF)-albumin/serum-albumin ratio, and interictal electroencephalograms (EEGs). Responder to MP was defined as maintaining seizure reduction rate (SRR) ≥50% for three months after the first course of MP. RESULTS: Thirty-one consecutive patients treated with MP at our center were studied. Seizure types were focal onset impaired awareness seizure (FIAS) only (n = 23), FIAS with epileptic spasms (ES) (n = 7), and ES only (n = 1). Responder rate was 32.2% (10/31 patients), and seizure-free rate was 9.7% (3/31). Responders constituted 43.5% of patients without ES. No patient with ES was responder. Behavior and cognition also improved in 6 of 10 responders. History of seizure aggravation after inactivated vaccine before MP was found significantly higher rate in responder patients, comparing with nonresponder patients (p = 0.01). CONCLUSION: Methylprednisolone pulse therapy may be considered for possible treatment in patients with focal epilepsy with drug-resistant seizures without ES, and it may improve cognitive function and behavioral comorbidities.