Faculty Bibliography

OBJECTIVE:This study was undertaken to evaluate the cross-cultural application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) to a cohort of Spanish-speaking patients with temporal lobe epilepsy (TLE) living in the United States. METHODS:Eighty-four Spanish-speaking patients with TLE completed neuropsychological measures of memory, language, executive function, visuospatial functioning, and attention/processing speed as part of the Neuropsychological Screening Battery for Hispanics. The contribution of demographic and clinical variables to cognitive performance was evaluated. A sensitivity analysis was conducted by examining the base rates of impairment across several impairment thresholds. The IC-CoDE taxonomy was then applied, and the base rate of cognitive phenotypes for each cutoff was calculated. The distribution of phenotypes was compared to the published IC-CoDE taxonomy data, which utilized a large, multicenter cohort of English-speaking patients with TLE. RESULTS:Across the different impairment cutoffs, memory was the most impaired cognitive domain, with impairments in list learning ranging from 50% to 78%. Application of the IC-CoDE taxonomy utilizing a -1.5-SD cutoff revealed an intact cognitive profile in 47.6% of patients, single-domain impairment in 23.8% of patients, bidomain impairment in 14.3% of patients, and generalized impairment in 14.3% of the sample. This distribution was comparable to the phenotype distribution observed in the IC-CoDE validation sample. SIGNIFICANCE/CONCLUSIONS:We demonstrate a similar pattern and distribution of cognitive phenotypes in a Spanish-speaking epilepsy cohort compared to an English-speaking sample. This suggests stability in the underlying phenotypes associated with TLE and applicability of the IC-CoDE for guiding cognitive diagnostics in epilepsy research that can be applied to culturally and linguistically diverse samples.

Pediatric neuropsychologists are increasingly recognizing the importance of performance validity testing during evaluations. The use of such measures to detect insufficient effort is of particular importance in pediatric epilepsy evaluations, where test results are often used to guide surgical decisions and failure to detect poor task engagement can result in postsurgical cognitive decline. The present investigation assesses the utility of the Medical Symptom Validity Test (MSVT) in 104 clinically referred children and adolescents with epilepsy. Though the overall failure rate was 15.4% of the total group, children with 2nd grade or higher reading skills (a requirement of the task) passed at a very high rate (96.6%). Of the three failures, two were unequivocally deemed true positives, while the third failed due to extreme somnolence during testing. Notably, for those with ≥2nd grade reading levels, MSVT validity indices were unrelated to patient age, intellectual functioning, or age of epilepsy onset, while modest relations were seen with specific memory measures, number of epilepsy medications, and seizure frequency. Despite these associations, however, this did not result in more failures in this population of children and adolescents with substantial neurologic involvement, as pass rates exceeded 92% for those with intellectual disability, high seizure frequency, high medication burden, and even prior surgical resection of critical memory structures.

The material-specific model for memory impairment predicts that verbal memory deficits are seen with left temporal seizures, and visual memory deficits are seen with right temporal seizures (Henkin et al., 2005). In pediatric epilepsy, seizure pathology has not always yielded the expected material-specific memory profiles. This study used the Wide Range Assessment of Memory and Learning-Second Edition (WRAML-2) to assess memory functioning among pediatric patients with epilepsy. The WRAML-2 was administered to 180 youth with epilepsy during their neuropsychological evaluations. Memory and recognition scores correlated significantly with epilepsy severity variables. There were no significant differences in verbal and visual memory and recognition index scores among patients with generalized epilepsy or among those with lateralized or localized electroencephalography (EEG) patterns and lesions on imaging. However, clinically meaningful verbal versus visual discrepancy scores were significantly related to lateralized abnormalities on EEG and magnetic resonance imaging (MRI) results. Most patients with right hemisphere pathology showed the expected material-specific visual memory deficits, while fewer than 15% of the left hemisphere cases showed the expected verbal memory deficits. Over one-third of those with identified left-sided pathology showed clinically significant deficits in visual memory. Findings are incongruent with the material-specific memory model and reflect the fact that early developmental neurological insults can lead to functional reorganization/crowding effects in children with left hemisphere epilepsy. On exploratory analyses, there were no significant differences in discrepancy scores among participants with left, right, and bilateral languages on Wada and functional MRI (fMRI). However, those with right and bilateral language dominance were more likely to show discrepancies that were incongruent with the material-specific model.

Several methods for identifying suboptimal effort on Spanish neuropsychological assessment have been established. The purpose of this retrospective study was to determine whether recognition data from the WHO-AVLT could be employed for determination of malingering in a Spanish-speaking sample. Sixteen subjects in litigation, 25 neurological patients, and 14 healthy controls completed neuropsychological testing. All subjects completed the Test of Memory Malingering (TOMM). Inclusion criteria for neurological patients and controls included performance above the standard TOMM cutoff. Subjects in litigation were classified as probable malingering, through lower than cutoff performance on the TOMM and at least one other performance validity measure. Cut-off scores for classification of malingering were determined based on the number of recognition hits on the WHO-AVLT. The probable malingering group performed significantly worse than both groups on recognition hits. A score <10 was determined to be the optimal group cutoff, with 56.25% sensitivity and specificity greater than 92%. A combination score of 14 increased sensitivity to 68.75%. These findings provide initial validation of a new malingering index, based on the number of hits on the WHO-AVLT recognition trial. This index will provide valuable information to neuropsychologists conducting forensic or clinical evaluations on Spanish-speaking individuals.

BACKGROUND:High heterogeneity in the CFTR gene mutations disturbs the molecular diagnosis of cystic fibrosis (CF). In order to improve the diagnosis of CF in our country, the present study aims to define a panel of common CFTR gene mutations by sequencing 27 exons of the gene in Ecuadorian Cystic Fibrosis patients. METHODS:Forty-eight Ecuadorian individuals with suspected/confirmed CF diagnosis were included. Twenty-seven exons of CFTR gene were sequenced to find sequence variations. Prevalence of pathogenic variations were determined and compared with other countries' data. RESULTS:We found 70 sequence variations. Eight of these are CF-causing mutations: p.F508del, p.G85E, p.G330E, p.A455E, p.G970S, W1098X, R1162X, and N1303K. Also this study is the second report of p.H609R in Ecuadorian population. Mutation prevalence differences between Ecuadorian population and other Latin America countries were found. CONCLUSION:The panel of mutations suggested as an initial screening for the Ecuadorian population with cystic fibrosis should contain the mutations: p.F508del, p.G85E, p.G330E, p.A455E, p.G970S, W1098X, R1162X, and N1303K.

Depression, common in chronic medical conditions, and hepatic encephalopathy (HE), a reversible neuropsychiatric syndrome due to liver dysfunction, are associated with impaired health-related quality of life (HRQOL) in cirrhosis and hepatitis C (HCV). This study investigated the impact of depression and HE on HRQOL in cirrhotic patients with HCV. A convenience sample of 43 ambulatory patients, with varying degrees of cirrhosis secondary to HCV, was prospectively enrolled in this study. Participants were assessed for any current depressive, fatigue, and daytime sleepiness symptoms and underwent a psychometric evaluation to determine the presence of HE symptoms. Participants reported current HRQOL on general health and liver disease-specific questionnaires. Diagnosis and current health status were confirmed via medical records. The associations between disease severity, depressive symptoms, HE, fatigue, and daytime sleepiness were measured. Predictors of HRQOL in this sample were determined. Depressive symptoms (70 %) and HE (77 %) were highly prevalent in this sample, with 58 % actively experiencing both conditions at the time of study participation. A significant positive association was found between depressive symptoms and HE severity (P = .05). Depressive symptoms were significantly associated with fatigue (P < .001), daytime sleepiness (P < .001), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). HE was significantly associated with fatigue (P = .02), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). Depressive symptoms and HE were significant predictors of reduced HRQOL (P < .001), with depressive symptoms alone accounting for 58.8 % of the variance. Depressive symptoms and HE accounted for 68.0 % of the variance. Findings suggest a possible pathophysiological link between depression and HE in cirrhosis, and potentially a wider-reaching benefit of treating minimal and overt HE than previously appreciated.

MOTIVATION:Boolean networks (BNs) are commonly used to model genetic regulatory networks (GRNs). Due to the sensibility of the dynamical behavior to changes in the updating scheme (order in which the nodes of a network update their state values), it is increasingly common to use different updating rules in the modeling of GRNs to better capture an observed biological phenomenon and thus to obtain more realistic models.In Aracena et al. equivalence classes of deterministic update schedules in BNs, that yield exactly the same dynamical behavior of the network, were defined according to a certain label function on the arcs of the interaction digraph defined for each scheme. Thus, the interaction digraph so labeled (update digraphs) encode the non-equivalent schemes. RESULTS:We address the problem of enumerating all non-equivalent deterministic update schedules of a given BN. First, we show that it is an intractable problem in general. To solve it, we first construct an algorithm that determines the set of update digraphs of a BN. For that, we use divide and conquer methodology based on the structural characteristics of the interaction digraph. Next, for each update digraph we determine a scheme associated. This algorithm also works in the case where there is a partial knowledge about the relative order of the updating of the states of the nodes. We exhibit some examples of how the algorithm works on some GRNs published in the literature. AVAILABILITY AND IMPLEMENTATION:An executable file of the UpdateLabel algorithm made in Java and the files with the outputs of the algorithms used with the GRNs are available at: www.inf.udec.cl/ ∼lilian/UDE/ CONTACT: lilisalinas@udec.cl SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.