To examine neurobehavioral findings in three genetic syndromes (PTEN hamartoma tumor syndrome, Malan syndrome [mutations in the NFIX gene], and SYNGAP1-related disorder), a mixed group of other neurodevelopmental genetic syndromes (NDGS), idiopathic neurodevelopmental disorder, and neurotypical control participants.
Abstract Objective Cognitive impairment is now recognized as an impending public health crisis. About one-third of adults are concerned about their cognition, and the prevalence of objective cognitive impairment is much higher among those with neurological disorders. Existing screening tools are narrowly focused on detecting dementia in older adults and must be clinician-administered and scored, making them impractical for many neurology practices. This study examined the utility of a brief, self-administered, computerized cognitive screening tool, the Brief Assessment of Cognitive Health (BACH), in identifying cognitive impairment in adults. Methods 912 adults (ages 18–84) completed BACH and a neuropsychological battery. Multivariable models were developed to provide a BACH index score reflecting the probability of cognitive impairment for individual patients. Predictive accuracy was compared to that of the Montreal Cognitive Assessment (MoCA) in a subset of 160 older adults from a Memory Disorders clinic. Results The final multivariable model showed good accuracy in identifying cognitively impaired individuals ( c = 0·77). Compared to MoCA, BACH had superior predictive accuracy in identifying older patients with cognitive impairment ( c = 0·79 vs. 0·67) as well as differentiating those with MCI or dementia from those without cognitive impairment ( c = 0·86 vs. c = 0·67). Conclusions Results suggest that cognitive impairment can be identified in adults using a brief, self-administered, automated cognitive screening tool, and BACH provides several advantages over existing screeners: self-administered; automatic scoring; immediate results in health record; easily interpretable score; utility in wide range of patients; and flags for treatable factors that may contribute to cognitive complaints (i.e., depression, sleep problems, and stress).
Abstract Background PTEN is a well-established risk gene for autism spectrum disorder (ASD). Yet, little is known about how PTEN mutations and associated molecular processes influence neurobehavioral function in mutation carriers with (PTEN-ASD) and without ASD (PTEN no-ASD). The primary aim of the present study was to examine group differences in peripheral blood-derived PTEN pathway protein levels between PTEN-ASD, PTEN no-ASD, and idiopathic macrocephalic ASD patients (macro-ASD). Secondarily, associations between protein levels and neurobehavioral functions were examined in the full cohort. Methods Patients were recruited at four tertiary medical centers. Peripheral blood-derived protein levels from canonical PTEN pathways (PI3K/AKT and MAPK/ERK) were analyzed using Western blot analyses blinded to genotype and ASD status. Neurobehavioral measures included standardized assessments of global cognitive ability and multiple neurobehavioral domains. Analysis of variance models examined group differences in demographic, neurobehavioral, and protein measures. Bivariate correlations, structural models, and statistical learning procedures estimated associations between molecular and neurobehavioral variables. To complement patient data, Western blots for downstream proteins were generated to evaluate canonical PTEN pathways in the PTEN-m3m4 mouse model. Results Participants included 61 patients (25 PTEN-ASD, 16 PTEN no-ASD, and 20 macro-ASD). Decreased PTEN and S6 were observed in both PTEN mutation groups. Reductions in MnSOD and increases in P-S6 were observed in ASD groups. Elevated neural P-AKT/AKT and P-S6/S6 from PTEN murine models parallel our patient observations. Patient PTEN and AKT levels were independently associated with global cognitive ability, and p27 expression was associated with frontal sub-cortical functions. As a group, molecular measures added significant predictive value to several neurobehavioral domains over and above PTEN mutation status. Limitations Sample sizes were small, precluding within-group analyses. Protein and neurobehavioral data were limited to a single evaluation. A small number of patients were excluded with invalid protein data, and cognitively impaired patients had missing data on some assessments. Conclusions Several canonical PTEN pathway molecules appear to influence the presence of ASD and modify neurobehavioral function in PTEN mutation patients. Protein assays of the PTEN pathway may be useful for predicting neurobehavioral outcomes in PTEN patients. Future longitudinal analyses are needed to replicate these findings and evaluate within-group relationships between protein and neurobehavioral measures. Trial registration ClinicalTrials.gov Identifier NCT02461446
Objective: Word finding or “naming” difficulty is a symptom of multiple neurological disorders; therefore, naming assessment is an integral component of neuropsychological evaluation. Prior work has found weaker second-language naming in healthy proficient bilingual youth than monolingual youth, and similar findings have been shown in adults with epilepsy. Considering the potential influences of both early onset epilepsy and bilingualism on brain development, we compared naming in English second language (ESL) and monolingual youth with epilepsy. To assess the impact of bilingualism independent of the known effects of seizure laterality (i.e., poor naming in those with left, dominant-hemisphere seizures), we excluded patients with left language dominance and unilateral seizures. We hypothesized that like other groups, naming would be weaker in ESL than in monolingual youth with epilepsy. Participants and Methods: Participants included 84 children with seizures that could not be lateralized clinically (n=36), bilateral seizures (n=20), centrotemporal spikes (n=3), and those with unilateral seizures and atypical language dominance (n=25), ages 6-15 years old: 66 monolingual, English (mean age: 10.87 ± 2.70 years) and 18 ESL (mean age: 10.78 ± 2.88 years). Those with FSIQ < 70 and vocabulary SS < 6 were excluded to ensure English proficiency. Independent samples t-tests, multivariate ANOVA, and chi-square tests compared groups on demographic factors and test performance. All measures (FSIQ, WISC/WASI Vocabulary, letter and category fluency, Children’s Auditory (AN) and Visual Naming (VN) Tests) were administered in English. Results: Monolingual and ESL groups did not differ in: age, sex, SES, seizure type (i.e., non-lateralized, bilateral, centrotemporal spikes, or atypical language dominance), epilepsy onset age, or number of AEDs. Comparisons also showed no differences in FSIQ, vocabulary, letter fluency, or category fluency (all ps > 0.05). By contrast, auditory and visual naming performances were weaker among ESL patients than monolingual patients: AN accuracy, F(1,81) = 10.89, p = 0.001; AN tip-of-the-tongues (TOTs), F(1,81) = 6.35, p = 0.014; AN Summary Scores (SS), F(1,81) = 6.17, p = 0.015; VN accuracy, F(1,81) = 4.66, p = 0.034; VN SS, F(1,81) = 4.87, p = 0.030, with the exception of VN TOTs, which approached significance, F(1,81) = 3.55, p = 0.063. Conclusions: Consistent with findings in bilingual healthy youth and ESL adults with epilepsy, naming in ESL youth with epilepsy was weaker than in monolingual children. The groups did not differ on other aspects of language. Thus, unlike other expressive verbal functions, naming is adversely affected in the second language of bilingual people with epilepsy across the age span. These results suggest that poor naming in ESL patients cannot be used to infer a naming deficit, and/or left (dominant) temporal lobe dysfunction.
Purpose To estimate the effect of integrating custom-designed hand therapy video games (HTVG) with contralaterally controlled functional electrical stimulation (CCFES) therapy.
This study sought to determine if word-finding difficulties (WFDs), which are common in adults with dominant temporal lobe epilepsy (TLE), are related to performance on verbal cognitive measures, including memory. One hundred six individuals with left TLE and pathologically confirmed mesial temporal sclerosis completed comprehensive preoperative neuropsychological evaluations. Patients were divided into two groups based on the degree of benefit received from phonemic cueing on a confrontation naming task. Cognitive performance was then compared between patients with greater and fewer WFDs. Patients with greater WFDs demonstrated poorer performance on many verbal cognitive measures compared to those with fewer WFDs. In contrast, there were no significant differences between groups on any of the nonverbal cognitive measures. Chi-square analyses indicated that below average verbal memory performance occurred at a significantly higher rate for patients with greater WFDs (42-46%) as compared to patients with fewer WFDs (18-24%). Results showed that WFDs confound performance on verbal cognitive measures in adult patients with left TLE, particularly on measures with high demands for lexical retrieval. This suggests that when patients have word-retrieval difficulties, measures of verbal memory and verbal intelligence may be underestimated and potentially lead to misinterpretation of test performance and misinformation regarding risk of declines after surgical resection.
The Boston Naming Test (BNT) is often used in the evaluation of surgical epilepsy patients to assess left temporal lobe function. In 2005, Busch et al. demonstrated the diagnostic utility of the BNT in predicting ultimate side of surgery in patients with temporal lobe epilepsy. BNT raw score significantly predicted ultimate side of surgery, moderated by Full Scale IQ (FSIQ), age at seizure onset, and duration of epilepsy. The final regression equation correctly predicted side of surgery in 69.5% of the sample. The current study demonstrated excellent cross-validation of this equation in an independent sample of 104 patients who eventually underwent temporal lobectomies, correctly predicting side of surgery in 67.3% of patients. The combination of the two samples resulted in a new, more-stable regression equation that correctly predicted side of surgery in 68.8% of the combined sample. These results further support the clinical utility of the BNT in predicting side of surgery.
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