Diagnostic accuracy of paroxysmal spells: Clinical history versus observation.

Our goal was to evaluate how accurate neurologists are at differentiating between different paroxysmal events based on clinical history versus observation of the spell in question. Forty-seven neurologists reviewed 12 clinical histories and videos of recorded events of patients admitted in the Epilepsy Monitoring Unit (EMU). They were asked to diagnose events as epileptic seizures, non-epileptic behavioral spells (NEBS), or other physiologic events as well as rate their confidence in their diagnosis. The median diagnostic accuracy for all paroxysmal events was 67% for clinical history and 75% for observation (p=.001). This was largely due to the difference in accuracy within the subgroup of patients with NEBS (67% history vs. 83% observation, p<.001). There were trends for higher diagnostic accuracy and increased inter-rater agreement with higher levels of training. Physicians with higher levels of training were more confident with diagnosis based on observation. In summary, reviewing videos of paroxysmal spells may improve diagnostic accuracy and enhance the evaluation of patients. Neurologists at all levels of training should encourage the recording and review of videos of recurrent spells to aid in medical decision-making especially when there is high concern that the spells in question are NEBS.

Short-term neurocognitive outcomes following anterior temporal lobectomy.

Changes in cognitive function are a well established risk of anterior temporal lobectomy (ATL). Deficits in verbal memory are a common postoperative finding, though a small proportion of patients may improve. Postoperative evaluation typically occurs after six to 12months. Patients may benefit from earlier evaluation to identify potential needs; however, the results of a formal neuropsychological assessment at an early postoperative stage are not described in the literature. We compared pre- and postoperative cognitive function for 28 right ATL and 23 left ATL patients using repeated measures ANOVA. Changes in cognitive function were compared to ILAE seizure outcome. The mean time to postoperative neuropsychological testing was 11.1weeks (SD=6.7weeks). There was a side×surgery interaction for the verbal tasks: immediate memory recall (F(1,33)=20.68, p<0.001), short delay recall (F(1,29)=4.99, p=0.03), long delay recall (F(1,33)=10.36, p=0.003), recognition (F(1,33)=5.69, p=0.02), and naming (F(1,37)=15.86, p<0.001). This indicated that the left ATL group had a significant decrement in verbal memory following surgery, while the right ATL group experienced a small but significant improvement. For the right ATL group, there was a positive correlation between ILAE outcome and improvement in immediate recall (r=-0.62, p=0.02) and long delay recall (r=-0.57, p=0.03). There was no similar finding for the left ATL group. This study demonstrates that short-interval follow-up is effective in elucidating postoperative cognitive changes. Right ATL was associated with improvement in verbal memory, while left ATL resulted in a decrement in performance. Improvement in the right ATL group was related to improved seizure outcome. Short-interval follow-up may lend itself to the identification of patients who could benefit from early intervention.

Thoughts, emotions, and dissociative features differentiate patients with epilepsy from patients with psychogenic nonepileptic spells (PNESs).

Psychogenic nonepileptic spells (PNESs) are often very difficult to treat, which may be, in part, related to the limited information known about what a person experiences while having PNESs. For this retrospective study, thoughts, emotions, and dissociative features during a spell were evaluated in 351 patients diagnosed with PNESs (N=223) or epilepsy (N=128). We found that a statistically higher number of thoughts, emotions, and dissociative symptoms were endorsed by patients with PNESs versus patients with epilepsy. Patients with PNESs reported significantly more anxiety and frustration, but not depression, compared with those with epilepsy. Emotions and dissociations, but not thoughts, and a history of any type of abuse were endorsed significantly more often by patients with PNESs. Patients with PNESs are prone to having poor outcomes, and interventions focusing on their actual experiences may be helpful for treatment planning.

Panic attack symptoms differentiate patients with epilepsy from those with psychogenic nonepileptic spells (PNES).

Psychogenic nonepileptic spells (PNES) are frequently challenging to differentiate from epileptic seizures. The experience of panic attack symptoms during an event may assist in distinguishing PNES from seizures secondary to epilepsy. A retrospective analysis of 354 patients diagnosed with PNES (N=224) or with epilepsy (N=130) investigated the thirteen Diagnostic and Statistical Manual-IV-Text Revision panic attack criteria endorsed by the two groups. We found a statistically higher mean number of symptoms reported by patients with PNES compared with those with epilepsy. In addition, the majority of the panic attack symptoms including heart palpitations, sweating, shortness of breath, choking feeling, chest discomfort, dizziness/unsteadiness, derealization or depersonalization, fear of dying, paresthesias, and chills or hot flashes were significantly more frequent in those with PNES. As patients with PNES frequently have poor clinical outcomes, treatment addressing the anxiety symptomatology may be beneficial.

Medical comorbidities in patients with psychogenic nonepileptic spells (PNES) referred for video-EEG monitoring.

Differentiating between psychogenic nonepileptic spells (PNES) and epileptic seizures without video-EEG monitoring is difficult. The presence of specific medical comorbidities may discriminate the two, helping physicians suspect PNES over epilepsy earlier. A retrospective analysis comparing the medical comorbidities of patients with PNES with those of patients with epilepsy was performed in 280 patients diagnosed with either PNES (N = 158, 74.7% females) or epilepsy (N = 122, 46.7% females) in the Epilepsy Monitoring Unit (EMU) of the University of Pittsburgh Medical Center over a two-year period. Patients with PNES, compared to those with epilepsy, were mostly female, significantly more likely to have a history of abuse, had more functional somatic syndromes (fibromyalgia, chronic fatigue syndrome, chronic pain syndrome, tension headaches, and irritable bowel syndrome), and had more medical illnesses that are chronic with intermittent attacks (migraines, asthma, and GERD). The presence of at least of one these disorders may lead physicians to suspect PNES over epilepsy and expedite appropriate referral for video-EEG monitoring for diagnosis.

Fractionation of cellulase and fermentation inhibitors from steam pretreated mixed hardwood.

The purpose of liquid hot water and steam pretreatment of wood is to fractionate hemicelluloses, partially solubilize lignin, and enhance enzyme hydrolysis of cellulose. The pretreatment also solubilizes sugar oligomers, lignin-derived phenolic compounds, acetic acid, and furan derivatives that inhibit cellulase enzymes and/or impede fermentation of hydrolysates by yeasts. This work extends knowledge of the relative contribution of identified inhibitors, and the effect of temperature on their release when pretreated materials are washed and filtered with hot water. Dramatic yield improvements occur when polymeric or activated carbon adsorbs and removes inhibitors. By desorbing, recovering, and characterizing adsorbed molecules we found phenolic compounds were strong inhibitors of enzyme hydrolysis and fermentation of concentrated filtrates by Saccharomyces cerevisiae wine yeast NRRL Y-1536 or xylose fermenting yeast 424A (LNH-ST). These data show that separation of inhibitors from pretreatment liquid will be important in achieving maximal enzyme activity and efficient fermentations.

Effect of compositional variability of distillers' grains on cellulosic ethanol production.

In a dry grind ethanol plant, approximately 0.84kg of dried distillers' grains with solubles (DDGS) is produced per liter of ethanol. The distillers' grains contain the unhydrolyzed and unprocessed cellulosic fraction of corn kernels, which could be further converted to ethanol or other valuable bioproducts by applying cellulose conversion technology. Its compositional variability is one of the factors that could affect the overall process design and economics. In this study, we present compositional variability of distillers' grains collected from four different dry grind ethanol plants and its effect on enzymatic digestibility and fermentability. We then selected two sources of distillers grains based on their distinctive compositional difference. These were pretreated by either controlled pH liquid hot water (LHW) or ammonia fiber expansion (AFEX) and subjected to enzymatic hydrolysis and fermentation. Fermentation of the pretreated distillers' grains using either industrial yeast or genetically engineered glucose and xylose co-fermenting yeast, yielded 70-80% of theoretical maximum ethanol concentration, which varied depending on the batch of distillers' grains used. Results show that cellulose conversion and ethanol fermentation yields are affected by the compositions of distillers' grains. Distillers' grains with a high extractives content exhibit a lower enzymatic digestibility but a higher fermentability.

Survey results of Internet and computer usage in veterans with epilepsy.

After our study of a self-management intervention for epilepsy, we gathered data on Internet use and computer availability to assess the feasibility of computer-based interventions in a veteran population. Veterans were asked to complete an anonymous questionnaire that gathered information regarding seizures/epilepsy in addition to demographic data, Internet use, computer availability, and interest in distance education regarding epilepsy. Three hundred twenty-four VA neurology clinic patients completed the survey. One hundred twenty-six self-reported a medical diagnosis of epilepsy and constituted the epilepsy/seizure group. For this group of veterans, the need for remote/distance-based interventions was validated given the majority of veterans traveled long distances (>2 hours). Only 51% of the epilepsy/seizure group had access to the Internet, and less than half (42%) expressed an interest in getting information on epilepsy self-management on their computer, suggesting that Web-based interventions may not be an optimal method for a self-management intervention in this population.

Liquid hot water pretreatment of cellulosic biomass.

Lignocellulosic biomass is an abundant and renewable resource for fuel ethanol production. However, the lignocellulose is recalcitrant to enzymatic hydrolysis because of its structural complexity. Controlled-pH liquid hot water (LHW) pretreatment of cellulosic feedstock improves its enzymatic digestibility by removing hemicellulose and making the cellulose more accessible to cellulase enzymes. The removed hemicellulose is solubilized in the liquid phase of the pretreated feedstock as oligosaccharides. Formation of monomeric sugars during the LHW pretreatment is minimal. The LHW pretreatment is carried out by cooking the feedstock in process water at temperatures between 160 and 190 degrees C and at a pH of 4-7. No additional chemicals are needed. This chapter presents the detailed procedure of the LHW pretreatment of lignocellulosic biomass.

Composition of corn dry-grind ethanol by-products: DDGS, wet cake, and thin stillage.

DDGS and wet distillers' grains are the major co-products of the dry grind ethanol facilities. As they are mainly used as animal feed, a typical compositional analysis of the DDGS and wet distillers' grains mainly focuses on defining the feedstock's nutritional characteristics. With an increasing demand for fuel ethanol, the DDGS and wet distillers' grains are viewed as a potential bridge feedstock for ethanol production from other cellulosic biomass. The introduction of DDGS or wet distillers' grains as an additional feed to the existing dry grind plants for increased ethanol yield requires a different approach to the compositional analysis of the material. Rather than focusing on its nutritional value, this new approach aims at determining more detailed chemical composition, especially on polymeric sugars such as cellulose, starch and xylan, which release fermentable sugars upon enzymatic hydrolysis. In this paper we present a detailed and complete compositional analysis procedure suggested for DDGS and wet distillers' grains, as well as the resulting compositions completed by three different research groups. Polymeric sugars, crude protein, crude oil and ash contents of DDGS and wet distillers' grains were accurately and reproducibly determined by the compositional analysis procedure described in this paper.

Enzyme hydrolysis and ethanol fermentation of liquid hot water and AFEX pretreated distillers' grains at high-solids loadings.

The dry milling ethanol industry produces distiller's grains as major co-products, which are composed of unhydrolyzed and unfermented polymeric sugars. Utilization of the distiller's grains as an additional source of fermentable sugars has the potential to increase overall ethanol yields in current dry grind processes. In this study, controlled pH liquid hot water pretreatment (LHW) and ammonia fiber expansion (AFEX) treatment have been applied to enhance enzymatic digestibility of the distiller's grains. Both pretreatment methods significantly increased the hydrolysis rate of distiller's dried grains with solubles (DDGS) over unpretreated material, resulting in 90% cellulose conversion to glucose within 24h of hydrolysis at an enzyme loading of 15FPU cellulase and 40 IU beta-glucosidase per gram of glucan and a solids loading of 5% DDGS. Hydrolysis of the pretreated wet distiller's grains at 13-15% (wt of dry distiller's grains per wt of total mixture) solids loading at the same enzyme reduced cellulose conversion to 70% and increased conversion time to 72h for both LHW and AFEX pretreatments. However, when the cellulase was supplemented with xylanase and feruloyl esterase, the pretreated wet distiller's grains at 15% or 20% solids (w/w) gave 80% glucose and 50% xylose yields. The rationale for supplementation of cellulases with non-cellulolytic enzymes is given by Dien et al., later in this journal volume. Fermentation of the hydrolyzed wet distiller's grains by glucose fermenting Saccharomyces cerevisiae ATCC 4124 strain resulted in 100% theoretical ethanol yields for both LHW and AFEX pretreated wet distiller's grains. The solids remaining after fermentation had significantly higher protein content and are representative of a protein-enhanced wet DG that would result in enhanced DDGS. Enhanced DDGS refers to the solid product of a modified dry grind process in which the distiller's grains are recycled and processed further to extract the unutilized polymeric sugars. Compositional changes of the laboratory generated enhanced DDGS are also presented and discussed.

A psychosocial self-management program for epilepsy: a randomized pilot study in adults.

OBJECTIVE: The goal of the work described here was to develop and pilot a theoretically based self-management intervention in adults with epilepsy. METHODS: A randomized, controlled trial examined intervention effectiveness of a 6-week psychosocial intervention designed to improve self-efficacy and quality of life for 61 adults with diagnosed epilepsy. Measures included the Quality of Life in Epilepsy-89 inventory (QOLIE-89), the Washington Psychosocial Seizure Inventory (WPSI), a locus of control scale (LOC), and the Epilepsy Self-Efficacy Scale-2000 (ESES). Group differences were examined between groups using analysis of covariance. RESULTS: There was a significant improvement in the QOLIE-89 Role Limitations-Emotional score in the treatment group at follow-up, but no significant differences in overall quality of life. Strong and significant correlations were observed between outcome measures. CONCLUSION: Although the intervention had little effect on improving overall quality of life, we observed promising trends in postintervention group comparisons linking self-efficacy and other psychosocial factors with quality of life. Intervention material can be modified for stage-based behavior change and retested in another study.

Cognitive correlates of brain MRI subcortical signal hyperintensities in non-demented elderly.

OBJECTIVE: To investigate the relationship between magnetic resonance imaging (MRI) subcortical gray and capsular (SGCH) and white matter hyperintensities (WMH) and cognitive functions in non-demented community dwelling elderly. METHODS: The severity of SGCH and WMH on proton density and T2 MR images in 16 subjects was scored using the semi-quantitative rating scale of Scheltens et al. (1993). A limited series of cognitive tests selected a priori were then correlated with severity of SGCH and WMH. RESULTS: Analysis demonstrated that severity of SGCH was inversely related to performance on the Digit Span (R = -0.64, p < 0.01) and the Stroop Color Word Tests (R = -0.64, p < 0.01). Severity of WMH was related to worsening performance on the Trail Making Test (R = 0.67, p < 0.005). CONCLUSIONS: These findings indicate that severity of WMH is negatively related to more pure executive cognitive functions, specifically set shifting, while severity of SGCH is inversely related to more basic functions of attention and working memory.

Cognitive correlates of alterations in acetylcholinesterase in Alzheimer's disease.

We recently reported findings of modest loss of cortical acetylcholinesterase (AChE) activity in patients with overall mild Alzheimer's disease (AD) using N-[11C]methyl-pi-peridin-4-yl propionate ([11C]PMP) AChE positron emission tomography (PET). To determine cognitive correlates of in vivo cortical AChE activity in patients with mild to moderate AD (n=15), and in normal controls (NC, n=12) using [11C]PMP AChE PET imaging. Mean cortical AChE activity in the AD subjects was mildly reduced (-11.1%) compared to the control subjects (P<0.05). Analysis of the cognitive data showed that mean cortical AChE activity was significantly associated with performance on a test of attention and working memory (WAIS-III Digit Span, R=0.46, P=0.01) but not with tests of delayed short or long-term memory functions. Similar findings were present when the analysis was limited to the temporal cortex. Cortical AChE activity is more robustly associated with functions of attention and working memory compared to performance on primary memory tests in AD.