Browsing by Subject "epilepsy"

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    An Atlas of the Quantitative Protein Expression of Anti-Epileptic-Drug Transporters, Metabolizing Enzymes and Tight Junctions at the Blood-Brain Barrier in Epileptic Patients.
    (Pharmaceutics, 2021-12) Sato, Risa; Ohmori, Kotaro; Umetsu, Mina; Takao, Masaki; Tano, Mitsutoshi; Grant, Gerald; Porter, Brenda; Bet, Anthony; Terasaki, Tetsuya; Uchida, Yasuo
    The purpose of the present study was to quantitatively elucidate the levels of protein expression of anti-epileptic-drug (AED) transporters, metabolizing enzymes and tight junction molecules at the blood-brain barrier (BBB) in the focal site of epilepsy patients using accurate SWATH (sequential window acquisition of all theoretical fragment ion spectra) proteomics. Brain capillaries were isolated from focal sites in six epilepsy patients and five normal brains; tryptic digests were produced and subjected to SWATH analysis. MDR1 and BCRP were significantly downregulated in the epilepsy group compared to the normal group. Out of 16 AED-metabolizing enzymes detected, the protein expression levels of GSTP1, GSTO1, CYP2E1, ALDH1A1, ALDH6A1, ALDH7A1, ALDH9A1 and ADH5 were significantly 2.13-, 6.23-, 2.16-, 2.80-, 1.73-, 1.67-, 2.47- and 2.23-fold greater in the brain capillaries of epileptic patients than those of normal brains, respectively. The protein expression levels of Claudin-5, ZO-1, Catenin alpha-1, beta-1 and delta-1 were significantly lower, 1.97-, 2.51-, 2.44-, 1.90- and 1.63-fold, in the brain capillaries of epileptic patients compared to those of normal brains, respectively. Consistent with these observations, leakage of blood proteins was also observed. These results provide for a better understanding of the therapeutic effect of AEDs and molecular mechanisms of AED resistance in epileptic patients.
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    Cortical stimulation mapping for localization of visual and auditory language in pediatric epilepsy patients.
    (Journal of neurosurgery. Pediatrics, 2019-11-08) Muh, Carrie R; Chou, Naomi D; Rahimpour, Shervin; Komisarow, Jordan M; Spears, Tracy G; Fuchs, Herbert E; Serafini, Sandra; Grant, Gerald A
    OBJECTIVE:To determine resection margins near eloquent tissue, electrical cortical stimulation (ECS) mapping is often used with visual naming tasks. In recent years, auditory naming tasks have been found to provide a more comprehensive map. Differences in modality-specific language sites have been found in adult patients, but there is a paucity of research on ECS language studies in pediatric patients. The goals of this study were to evaluate word-finding distinctions between visual and auditory modalities and identify which cortical subregions most often contain critical language function in a pediatric population. METHODS:Twenty-one pediatric patients with epilepsy or temporal lobe pathology underwent ECS mapping using visual (n = 21) and auditory (n = 14) tasks. Fisher's exact test was used to determine whether the frequency of errors in the stimulated trials was greater than the patient's baseline error rate for each tested modality and subregion. RESULTS:While the medial superior temporal gyrus was a common language site for both visual and auditory language (43.8% and 46.2% of patients, respectively), other subregions showed significant differences between modalities, and there was significant variability between patients. Visual language was more likely to be located in the anterior temporal lobe than was auditory language. The pediatric patients exhibited fewer parietal language sites and a larger range of sites overall than did adult patients in previously published studies. CONCLUSIONS:There was no single area critical for language in more than 50% of patients tested in either modality for which more than 1 patient was tested (n > 1), affirming that language function is plastic in the setting of dominant-hemisphere pathology. The high rates of language function throughout the left frontal, temporal, and anterior parietal regions with few areas of overlap between modalities suggest that ECS mapping with both visual and auditory testing is necessary to obtain a comprehensive language map prior to epileptic focus or tumor resection.
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    Intraoperative microseizure detection using a high-density micro-electrocorticography electrode array.
    (Brain communications, 2022-01) Sun, James; Barth, Katrina; Qiao, Shaoyu; Chiang, Chia-Han; Wang, Charles; Rahimpour, Shervin; Trumpis, Michael; Duraivel, Suseendrakumar; Dubey, Agrita; Wingel, Katie E; Rachinskiy, Iakov; Voinas, Alex E; Ferrentino, Breonna; Southwell, Derek G; Haglund, Michael M; Friedman, Allan H; Lad, Shivanand P; Doyle, Werner K; Solzbacher, Florian; Cogan, Gregory; Sinha, Saurabh R; Devore, Sasha; Devinsky, Orrin; Friedman, Daniel; Pesaran, Bijan; Viventi, Jonathan
    One-third of epilepsy patients suffer from medication-resistant seizures. While surgery to remove epileptogenic tissue helps some patients, 30-70% of patients continue to experience seizures following resection. Surgical outcomes may be improved with more accurate localization of epileptogenic tissue. We have previously developed novel thin-film, subdural electrode arrays with hundreds of microelectrodes over a 100-1000 mm2 area to enable high-resolution mapping of neural activity. Here, we used these high-density arrays to study microscale properties of human epileptiform activity. We performed intraoperative micro-electrocorticographic recordings in nine patients with epilepsy. In addition, we recorded from four patients with movement disorders undergoing deep brain stimulator implantation as non-epileptic controls. A board-certified epileptologist identified microseizures, which resembled electrographic seizures normally observed with clinical macroelectrodes. Recordings in epileptic patients had a significantly higher microseizure rate (2.01 events/min) than recordings in non-epileptic subjects (0.01 events/min; permutation test, P = 0.0068). Using spatial averaging to simulate recordings from larger electrode contacts, we found that the number of detected microseizures decreased rapidly with increasing contact diameter and decreasing contact density. In cases in which microseizures were spatially distributed across multiple channels, the approximate onset region was identified. Our results suggest that micro-electrocorticographic electrode arrays with a high density of contacts and large coverage are essential for capturing microseizures in epilepsy patients and may be beneficial for localizing epileptogenic tissue to plan surgery or target brain stimulation.
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    MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation.
    (Cell reports, 2021-04) Swahari, Vijay; Nakamura, Ayumi; Hollville, Emilie; Stroud, Hume; Simon, Jeremy M; Ptacek, Travis S; Beck, Matthew V; Flowers, Cornelius; Guo, Jiami; Plestant, Charlotte; Liang, Jie; Kurtz, C Lisa; Kanke, Matt; Hammond, Scott M; He, You-Wen; Anton, ES; Sethupathy, Praveen; Moy, Sheryl S; Greenberg, Michael E; Deshmukh, Mohanish
    Although embryonic brain development and neurodegeneration have received considerable attention, the events that govern postnatal brain maturation are less understood. Here, we identify the miR-29 family to be strikingly induced during the late stages of brain maturation. Brain maturation is associated with a transient, postnatal period of de novo non-CG (CH) DNA methylation mediated by DNMT3A. We examine whether an important function of miR-29 during brain maturation is to restrict the period of CH methylation via its targeting of Dnmt3a. Deletion of miR-29 in the brain, or knockin mutations preventing miR-29 to specifically target Dnmt3a, result in increased DNMT3A expression, higher CH methylation, and repression of genes associated with neuronal activity and neuropsychiatric disorders. These mouse models also develop neurological deficits and premature lethality. Our results identify an essential role for miR-29 in restricting CH methylation in the brain and illustrate the importance of CH methylation regulation for normal brain maturation.