Electroencephalogram (EEG) time series classification: Applications in epilepsy

Epilepsy is among the most common brain disorders. Approximately 25–30% of epilepsy patients remain unresponsive to anti-epileptic drug treatment, which is the standard therapy for epilepsy. In this study, we apply optimization-based data mining techniques to classify the brain's normal and epilepsy activity using intracranial electroencephalogram (EEG), which is a tool for evaluating the physiological state of the brain. A statistical cross validation and support vector machines were implemented to classify the brain's normal and abnormal activities. The results of this study indicate that it may be possible to design and develop efficient seizure warning algorithms for diagnostic and therapeutic purposes. Research was partially supported by the Rutgers Research Council grant-202018, the NSF grants DBI-980821, CCF-0546574, IIS-0611998, and NIH grant R01-NS-39687-01A1.     

Quick stabilization of capillary for rapid determination of potassium ions in the blood of epilepsy patients by capillary electrophoresis without sample pretreatment

Mutations in the potassium channel genes may be linked to the development of epilepsy and affect the blood potassium levels. Therefore, accurate determination of potassium in the blood will be critical to diagnose the cause of epilepsy. CE is a competent technique for the fast detection of multiple ions, but complicated matrices of a blood sample may cause significant variation of migration times and the peak shape. In this work, a procedure for rapid stabilization of the capillary inner surface through preflushing of a blood sample was employed. The process takes only 40 min for a capillary and then it can be used for more than 2 weeks. No pretreatment of the blood sample or other surface modification of the capillary is needed for the analysis. The RSDs of the migration time and peak area were reduced to 1.5 and 5.1% from 12.6 and 14.5%, respectively. The proposed method has been successfully applied to the determination of the potassium contents in the blood sample of patients with epilepsy at different stages. The recoveries of potassium ions in these blood samples are in a range from 86.5 to 104.5%.     

Application of high field spectroscopic imaging in the evaluation of temporal lobe epilepsy

Previous spectroscopic imaging studies of temporal lobe epilepsy have used comparisons of metabolite content or ratios to lateralize the seizure focus. Although highly successful, these studies have shown significant variations within each of the groups of healthy subjects and patients. This variation may arise from the natural differences seen in metabolite concentration in gray and white matter, the complex anatomy seen about the hippocampus, and the large voxels typically employed at 1.5 T. Using a 4.1 T whole body system, we have acquired spectroscopic images with 0.5 cc nominal voxels (1 cc after filtering) to evaluate the regional variation in metabolite content of the hippocampus, temporal gray and white matter, midbrain, and cerebellar vermis. Using a threshold value of 0.90 for CR/NAA, a value 90% of all normal hippocampal voxels lay below, we have correctly identified the presence of epileptogenic tissue in patients with unilateral as well as bilateral seizures. By using comparisons to healthy values of the CR/NAA ratio, this method enables the visualization of bilateral disease and provides information on the extent of gray matter involvement.     

Proton magnetic resonance spectroscopic images and MRI volumetric studies for lateralization of temporal lobe epilepsy

We obtained 2D magnetic resonance (MR) spectroscopic images (MRSI) and MRI volumetric measurements (MRIV) of amygdala and hippocampus in 30 consecutive patients with temporal lobe epilepsy (TLE) being evaluated for surgical treatment. Both MRSI and MRIV lateralization showed good agreement with the current gold standard of clinical-EEG lateralization. Each exam separately correctly lateralized 25 out of 30 patients with no false lateralization. Combining both exams, lateralization could be achieved in 28 out of 30 patients. The two patients with no significant asymmetry had bitemporal EEG abnormalities, and bilateral damage on both MRIV and MRSI. There was a good correlation between the magnitude of the MRSI and MRIV asymmetry (Pearson COEFFICIENT = 0.83; p < .0001). Both MRSI and MRIV were normal in our patients with seizures originating outside the temporal lobes. Both MRIV and MRSI can lateralize TLE in 83% of patients. Combination of the two modalities allows lateralization in 93% of patients. Patients who cannot be lateralized generally have symmetrical bitemporal abnormalities; they are not incorrectly lateralized. The structural and chemical pathologic abnormalities seen in TLE seem to be associated with the seizure focus, and may be as, or even more, reliable than a few recorded seizures in predicting the side from which most seizures originate.     

Development of membrane electrodes for selective determination of some antiepileptic drugs in pharmaceuticals,plasma and urine

Newly developed, simple, low-cost and sensitive ion-selective electrodes have been proposed for determination of some antiepileptic drugs such as lamotrigine, felbamate, and primidone in their pharmaceutical preparations as well as in biological fluids. The electrodes are based on poly(vinyl chloride) membranes doped with drug–tetraphenyl borate (TPB) or drug–phosphotungstic acid (PT) ion-pair complexes as molecular recognition materials. The novel electrodes displayed rapid Nernstian responses with detection limits of approximately 10⁻⁷ M. Calibration graphs were linear over the ranges 5.2 × 10⁻⁷–1.0 × 10⁻³, 1.5 × 10⁻⁶–1.0 × 10⁻³, and 2.6 × 10⁻⁷–1.0 × 10⁻³ M for drug–TPB and 5.8 × 10⁻⁷–1.0 × 10⁻³, 1.8 × 10⁻⁷–1.0 × 10⁻³, and 6.6 × 10⁻⁷–1.0 × 10⁻³ M for drug–PT electrodes, respectively, with slopes ranging from 52.3 to 62.3 mV/decade. The membranes developed have potential stability for up to 1 month and proved to be highly selective for the drugs investigated over other ions and excipients. The results show that the selectivity of the ion-selective electrodes is influenced significantly by the plasticizer. The proposed electrodes were successfully applied in the determination of these drugs in pharmaceutical preparations in four batches of different expiry dates. Statistical Student’s t test and F test showed insignificant systematic error between the ion-selective electrode methods developed and a standard method. Comparison of the results obtained using the proposed electrodes with those found using a reference method showed that the ion-selective electrode technique is sensitive, reliable, and can be used with very good accuracy and high percentage recovery without pretreatment procedures of the samples to minimize interfering matrix effects. Figure Structure of lamotrigine, felbanate and primidone     

癫痫大鼠海马神经元生化分子的同步辐射显微红外光谱成像研究

癫痫是影响所有年龄段的慢性脑功能障碍,主要特征为整个或局部脑区神经元异常同步化高频群集动作电位发放。利用神经毒素海人藻酸（KA）立体定位注射入大鼠海马,诱导大鼠产生癫痫持续状态,建立颞叶癫痫大鼠模型。应用同步辐射显微光谱和同步辐射显微光谱成像分析癫痫持续状态发作后24小时的颞叶癫痫大鼠海马角（CA）1区神经元生物化学分子的胞内浓度和分布是否改变。结果显示反映蛋白质二级结构的酰胺Ⅰ在1 655 cm-1的振动频率和属于脂类功能集团的2 800～3 000 cm-1振动频率,在正常对照大鼠海马CA1神经元胞体内呈高浓度分布,但在癫痫大鼠海马CA1神经元胞体,反映蛋白质二级内呈低浓度分布,并且以细胞核分布浓度最低,但在神经元胞体外围分布浓度相对较高。属于核酸集团的1 055～1 054 cm-1 PO₂反对称拉伸振动在正常和癫痫大鼠海马CA1神经元胞体内分布趋势没有差异,都在胞体内呈高浓度分布,尤其在细胞核分布浓度最高。对属于酰胺Ⅰ的吸收频率进行二级导数分析显示癫痫海马神经元的酰胺Ⅰ相对于正常对照多出1个1 653 cm-1附近的负峰。以上结果提示在发生癫痫持续发作后海马神经元生物化学分子的细胞分布会出现变化。     

Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability

Response surface methodology (RSM) was used to optimize the formulation of a nanoemulsion for central delivery following parenteral administration. A mixture of medium-chain triglyceride (MCT) and safflower seed oil (SSO) was determined as a sole phase from the emulsification properties. Similarly, a natural surfactant (lecithin) and non-ionic surfactant (Tween 80) (ratio 1:2) were used in the formulation. A central composite design (CCD) with three-factor at five-levels was used to optimize the processing method of high energy ultrasonicator. Effects of pre-sonication ultrasonic intensity (A), sonication time (B), and temperature (C) were studied on the preparation of nanoemulsion loaded with valproic acid. Influence of the aforementioned specifically the effects of the ultrasonic processing parameters on droplet size and polydispersity index were investigated. From the analysis, it was found that the interaction between ultrasonic intensity and sonication time was the most influential factor on the droplet size of nanoemulsion formulated. Ultrasonic intensity (A) significantly affects the polydispersity index value. With this optimization method, a favorable droplet size of a nanoemulsion with reasonable polydispersity index was able to be formulated within a short sonication time. A valproic acid loaded nanoemulsion can be obtained with 60% power intensity for 15 min at 60 °C. Droplet size of 43.21 ± 0.11 nm with polydispersity index of 0.211 were produced. The drug content was then increased to 1.5%. Stability study of nanoemulsion containing 1.5% of valproic acid had a good stability as there are no significant changes in physicochemical aspects such as droplet size and polydispersity index. With the characteristisation study of pH, viscosity, transmission electron microscope (TEM) and stability assessment study the formulated nanoemulsion has the potential to penetrate blood–brain barrier in the treatment of epilepsy.     

Automated data processing of [1H-decoupled] 13C MR spectra acquired from human brain in vivo

In clinical 13C infusion studies, broadband excitation of 200 ppm of the human brain yields 13C MR spectra with a time resolution of 2-5 min and generates up to 2000 metabolite peaks over 2h. We describe a fast, automated, observer-independent technique for processing [1H-decoupled] 13C spectra. Quantified 13C spectroscopic signals, before and after the administration of [1-13C]glucose and/or [1-13C]acetate in human subjects are determined. Stepwise improvements of data processing are illustrated by examples of normal and pathological results. Variation in analysis of individual 13C resonances ranged between 2 and 14%. Using this method it is possible to reliably identify subtle metabolic effects of brain disease including Alzheimer's disease and epilepsy.     

Pore structures in an implantable sol-gel titania ceramic device used in controlled drug release applications: A modeling study

Several process variables, which may be helpful in optimizing the rate at which drugs are released from implantable, sol-gel titania devices have been identified in this study. The controlled rate of drug release is compared for two different anticonvulsant drugs, valproic acid and sodic phenytoin. Contrary to what one might expect, when the concentration is increased in the titania reservoir the rate of initial drug delivery decreases. This is a desirable result, because it may reduce the danger of a high initial discharge, which may harm the epileptic rat. The structure of the porous structure within the titania network has been studied using a generalized form of the BET equation which considers only n layers. In general, following an initial discharge, the rate at which the drug is released will increase with the increasing concentration. Pore mouth blocking can present a problem. However, this problem tends to disappear following the initial discharge. The extent of drug loading is a useful variable parameter, which can be adjusted in order to deliver the amount of drug required in a given application.     

儿童癫痫与微量元素关系初探

测定42例癫痫病患儿血中必需微量元素及有害元素，对其含量变化与临床症状间的关系进行分析研究，表明人体内微量元素失衡对本病的发生发展起重要作用．