Clinical recommendations for conducting pediatric functional language and memory mapping during the phase I epilepsy presurgical workup.

Objective: Pediatric epilepsy surgery effectively controls seizures but may risk cognitive, language, or memory decline. Historically, the intra-carotid anesthetic procedure (IAP or Wada Test) was pivotal for language and memory function. However, advancements in noninvasive mapping, notably functional magnetic resonance imaging (fMRI), have transformed clinical practice, reducing IAP's role in presurgical evaluations. Method: We conducted a critical narrative review on mapping technologies, including factors to consider for discordance. Results: Neuropsychological findings suggest that if pre-surgery function remains intact and the surgery targets the eloquent cortex, there is a high chance for decline. Memory and language decline are particularly pronounced post-left anterior temporal lobe resection (ATL), making presurgical cognitive assessment crucial for predicting postoperative outcomes. However, the risk of functional decline is not always clear - particularly with higher rates of atypical organization in pediatric epilepsy patients and discordant findings from cognitive mapping. We found little research to date on the use of IAP and other newer technologies for lateralization/localization in pediatric epilepsy. Based on this review, we introduce an IAP decision tree to systematically navigate discordance in IAP decisions for epilepsy presurgical workup. Conclusions: Future research should be aimed at pediatric populations to improve the precision of functional mapping, determine which methods predict post-surgical deficits and then create evidence-based practice guidelines to standardize mapping procedures. Explicit directives are needed for resolving conflicts between developing mapping procedures and established clinical measures. The proposed decision tree is the first step to standardize when to consider IAP or invasive mapping, in coordination with the multidisciplinary epilepsy surgical team.

Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children.

Importance: Acute neurological involvement occurs in some patients with multisystem inflammatory syndrome in children (MIS-C), but few data report neurological and psychological sequelae, and no investigations include direct assessments of cognitive function 6 to 12 months after discharge. Objective: To characterize neurological, psychological, and quality of life sequelae after MIS-C. Design, Setting, and Participants: This cross-sectional cohort study was conducted in the US and Canada. Participants included children with MIS-C diagnosed from November 2020 through November 2021, 6 to 12 months after hospital discharge, and their sibling or community controls, when available. Data analysis was performed from August 2022 to May 2023. Exposure: Diagnosis of MIS-C. Main Outcomes and Measures: A central study site remotely administered a onetime neurological examination and in-depth neuropsychological assessment including measures of cognition, behavior, quality of life, and daily function. Generalized estimating equations, accounting for matching, assessed for group differences. Results: Sixty-four patients with MIS-C (mean [SD] age, 11.5 [3.9] years; 20 girls [31%]) and 44 control participants (mean [SD] age, 12.6 [3.7] years; 20 girls [45%]) were enrolled. The MIS-C group exhibited abnormalities on neurological examination more frequently than controls (15 of 61 children [25%] vs 3 of 43 children [7%]; odds ratio, 4.7; 95% CI, 1.3-16.7). Although the 2 groups performed similarly on most cognitive measures, the MIS-C group scored lower on the National Institutes of Health Cognition Toolbox List Sort Working Memory Test, a measure of executive functioning (mean [SD] scores, 96.1 [14.3] vs 103.1 [10.5]). Parents reported worse psychological outcomes in cases compared with controls, particularly higher scores for depression symptoms (mean [SD] scores, 52.6 [13.1] vs 47.8 [9.4]) and somatization (mean [SD] scores, 55.5 [15.5] vs 47.0 [7.6]). Self-reported (mean [SD] scores, 79.6 [13.1] vs 85.5 [12.3]) and parent-reported (mean [SD] scores, 80.3 [15.5] vs 88.6 [13.0]) quality of life scores were also lower in cases than controls. Conclusions and Relevance: In this cohort study, compared with contemporaneous sibling or community controls, patients with MIS-C had more abnormal neurologic examinations, worse working memory scores, more somatization and depression symptoms, and lower quality of life 6 to 12 months after hospital discharge. Although these findings need to be confirmed in larger studies, enhanced monitoring may be warranted for early identification and treatment of neurological and psychological symptoms.

Is formal scoring better than just looking? A comparison of subjective and objective scoring methods of the Rey Complex Figure Test for lateralizing temporal lobe epilepsy.

ObjectiveNeuropsychologists labor over scoring the Rey Complex Figure Test (RCFT), a measure of visuospatial functioning and nonverbal memory. Compelling arguments suggest that pathognomonic signs of the RCFT are observable to the "naked eye." Standard scoring systems are insensitive to lateralizing temporal lobe epilepsy (TLE) and alternative "qualitative" scoring systems are ineffective and time-consuming. Method: We examined accuracy of TLE lateralization using subjective classifications and standard scoring. Participants were 84 TLE patients (53 female; mean age=36yrs) and 46 controls (27 female; mean age = 27.5). The former were classified as right (n = 41) or left (n = 43) TLE by neurologists using EEG and MRI studies. RCFT were scored using standard scoring with cut-offs of z ≤ -2 classified as impaired and were rated as "characteristic" of RTLE (Ugly) or LTLE (Not Ugly) performance by neuropsychologists. Accuracy of seizure lateralization for both methods was examined. Results: Neuropsychologists' ratings accuracy were at or below chance. Standard scoring criteria showed chance or slightly better lateralization prediction. Standard scoring predicted RTLE laterality more accurately than subjective ratings for copy trials; standard scoring was no better at lateralizing RTLE with delays. Subjective ratings were better at distinguishing TLE patients from controls. Conclusion: Findings highlight concerns regarding the usefulness of the RCFT in TLE lateralization, regardless of scoring approach.

The Utility of the Repeatable Battery of Neuropsychological Status in Patients with Temporal and Non-temporal Lobe Epilepsy.

OBJECTIVE: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a brief neuropsychological battery that has been validated in the assessment of dementia and other clinical populations. The current study examines the utility of the RBANS in patients with epilepsy. METHODS: Ninety-eight patients with epilepsy completed the RBANS as part of a more comprehensive neuropsychological evaluation. Performance on the RBANS was evaluated for patients with a diagnosis of temporal lobe epilepsy (TLE; n = 51) and other epilepsy patients (non-TLE, n = 47) in comparison to published norms. Multivariate analysis of variance compared group performances on RBANS indices. Rates of impairment were also compared across groups using cutoff scores of ≤1.0 and ≤1.5 standard deviations below the normative mean. Exploratory hierarchical regressions were used to examine the relations between epilepsy severity factors (i.e., age of onset, disease duration, and number of antiepileptic drugs [AEDs]) and RBANS performance. RESULTS: TLE and non-TLE patients performed below the normative sample across all RBANS indices. Those with TLE performed worse than non-TLE patients on the Immediate and Delayed Memory indices and exhibited higher rates of general cognitive impairment. Number of AEDs was the only epilepsy severity factor that significantly predicted RBANS total performance, accounting for 14% of the variance. CONCLUSIONS: These findings suggest that the RBANS has utility in evaluating cognition in patients with epilepsy and can differentiate TLE and non-TLE patients. Additionally, number of AEDs appears to be associated with global cognitive performance in adults with epilepsy.

The WISC-V in children and adolescents with epilepsy.

Despite its popularity in the neuropsychological evaluation of children, the utility of the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) has not yet been investigated in children with epilepsy. Eighty clinically referred children and adolescents with epilepsy were administered the WISC-V as part of a comprehensive assessment and scores were compared to matched controls from the WISC-V standardization sample. T tests compared WISC-V indices and subtests between patients and controls and Chi-square analyses compared the rates of low scores. Correlational analyses assessed the relationships between epilepsy severity variables (e.g., age of onset, duration of epilepsy, number of antiepileptic drugs, seizure frequency). All WISC-V composites and subtests were significantly lower in patients versus controls and the rate of low scores was higher in patients than controls for all composites and subtests with the exception of Figure Weights. The Working Memory Index and Processing Speed Index were most sensitive to impairment, while the Verbal Comprehension Index and Fluid Reasoning Index were least sensitive. Of the epilepsy severity variables, age of seizure onset and number of antiepileptic drugs were strong predictors of deficits, whereas seizure frequency was the weakest predictor. Importantly, no significant differences were seen in children with right hemisphere epilepsy versus left on the five WISC-V composites, though a trend was seen towards a lower Visual-Spatial Index in those with right-sided focal seizures.

Reliable Digit Span: Does it Adequately Measure Suboptimal Effort in an Adult Epilepsy Population?

OBJECTIVE: Assessment of performance validity is a necessary component of any neuropsychological evaluation. Prior research has shown that cutoff scores of ≤6 or ≤7 on Reliable Digit Span (RDS) can detect suboptimal effort across numerous adult clinical populations; however, these scores have not been validated for that purpose in an adult epilepsy population. This investigation aims to determine whether these previously established RDS cutoff scores could detect suboptimal effort in adults with epilepsy. METHOD: Sixty-three clinically referred adults with a diagnosis of epilepsy or suspected seizures were administered the Digit Span subtest of the Wechsler Adult Intelligence Scale (WAIS-III or WAIS-IV). Most participants (98%) passed Trial 2 of the Test of Memory Malingering (TOMM), achieving a score of ≥45. RESULTS: Previously established cutoff scores of ≤6 and ≤7 on RDS yielded a specificity rate of 85% and 77% respectively. Findings also revealed that RDS scores were positively related to attention and intellectual functioning. Given the less than ideal specificity rate associated with each of these cutoff scores, together with their strong association to cognitive factors, secondary analyses were conducted to identify more optimal cutoff scores. Preliminary results suggest that an RDS cutoff score of ≤4 may be more appropriate in a clinically referred adult epilepsy population with a low average IQ or lower. CONCLUSIONS: Preliminary findings indicate that cutoff scores of ≤6 and ≤7 on RDS are not appropriate in adults with epilepsy, especially in individuals with low average IQ or below.

Phonemic and Semantic Verbal Fluency in Sex Chromosome Aneuploidy: Contrasting the Effects of Supernumerary X versus Y Chromosomes on Performance.

OBJECTIVES: Past research suggests that youth with sex chromosome aneuploidies (SCAs) present with verbal fluency deficits. However, most studies have focused on sex chromosome trisomies. Far less is known about sex chromosome tetrasomies and pentasomies. Thus, the current research sought to characterize verbal fluency performance among youth with sex chromosome trisomies, tetrasomies, and pentasomies by contrasting how performance varies as a function of extra X number and X versus Y status. METHODS: Participants included 79 youth with SCAs and 42 typically developing controls matched on age, maternal education, and racial/ethnic background. Participants completed the phonemic and semantic conditions of a verbal fluency task and an abbreviated intelligence test. RESULTS: Both supernumerary X and Y chromosomes were associated with verbal fluency deficits relative to controls. These impairments increased as a function of the number of extra X chromosomes, and the pattern of impairments on phonemic and semantic fluency differed for those with a supernumerary X versus Y chromosome. Whereas one supernumerary Y chromosome was associated with similar performance across fluency conditions, one supernumerary X chromosome was associated with relatively stronger semantic than phonemic fluency skills. CONCLUSIONS: Verbal fluency skills in youth with supernumerary X and Y chromosomes are impaired relative to controls. However, the degree of impairment varies across groups and task condition. Further research into the cognitive underpinnings of verbal fluency in youth with SCAs may provide insights into their verbal fluency deficits and help guide future treatments. (JINS, 2018, 24, 917-927).

Sensitivity of the Wisconsin Card Sorting Test (64-Card Version) versus the Tower of London (Drexel Version) for detecting executive dysfunction in children with epilepsy.

Executive function deficits are common in children and adolescents with epilepsy. Though the Wisconsin Card Sorting Task (WCST) is often considered the "gold standard" for executive function assessment, its sensitivity-particularly in the case of the 64-card version (WCST-64)-is insufficiently established in pediatric samples, including children and adolescents with epilepsy. The present investigation assesses the sensitivity of the WCST-64 in children and adolescents with epilepsy in comparison to another measure: the Tower of London - Drexel Version (TOL-DX). A total of 88 consecutively referred children and adolescents with epilepsy were administered both the WCST-64 and TOL-DX as part of a comprehensive neuropsychological evaluation. The sensitivity of WCST-64 and TOL-DX variables were established and relations with epilepsy severity measures and other executive function measures were assessed. Of the WCST-64 variables, Perseverative Responses is the most sensitive, but detected executive function impairment in only 19% of this clinically referred sample; in contrast, the TOL-DX Rule Violations detected executive function impairment in half of the sample. Further, TOL-DX performances are more strongly related to epilepsy severity variables and other executive function measures in comparison to the WCST-64. Despite its popularity amongst clinicians, the WCST-64 is not as sensitive to executive dysfunction in comparison to other measures of comparable administration time, such as the TOL-DX.

Utility of the Behavior Rating Inventory of Executive Function - Preschool version (BRIEF-P) in young children with epilepsy.

Executive functioning deficits are prominent in children with epilepsy. Although instruments, such as the Behavior Rating Inventory of Executive Function (BRIEF), are useful in detecting executive dysfunction in school-age children with epilepsy, little data are available for younger children. The present study evaluates the ability of the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P) to detect executive dysfunction in preschool-age children with epilepsy. Parents of 51 clinically referred children with epilepsy (age: M = 1.99 years, SD = 1.29 years, range = 2-5 years) completed the BRIEF-P. Using a cutoff t score of ≥65 as the threshold for impairment, the BRIEF-P's ability to detect executive dysfunction within this clinical population was established. Additionally, correlational analyses were used to assess the relations between epilepsy severity factors and BRIEF-P indices. Epilepsy severity variables that were significantly related to BRIEF-P indices were entered into a linear regression model to explore their predictive ability. Emergent metacognition (emergent metacognition index [EMI]; 59%) and the global executive composite (43%) were the most frequently elevated indices. The most commonly elevated subscales were working memory (65%), inhibition (37%), and planning/organization (35%). Age of seizure onset, seizure frequency, and number of antiepileptic drugs were not significantly correlated with BRIEF-P indices. However, children with lower intellectual ability were rated as having greater executive dysfunction, specifically with EMI (r = -.30). Still, intellectual functioning only accounted for a small percentage (9%) of the variance in EMI scores. The current pilot study demonstrates that the BRIEF-P shows promise in identifying executive dysfunction in preschool-age children with epilepsy.

Increased odds and predictive rates of MMPI-2-RF scale elevations in patients with psychogenic non-epileptic seizures and observed sex differences.

OBJECTIVE: The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a self-report instrument, previously shown to differentiate patients with epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES). At present, the odds of MMPI-2-RF scale elevations in PNES patients, as well as the diagnostic predictive value of such scale elevations, remain largely unexplored. This can be of clinical utility, particularly when a diagnosis is uncertain. METHOD: After looking at mean group differences, we applied contingency table derived odds ratios to a sample of ES (n=92) and PNES (n=77) patients from a video EEG (vEEG) monitoring unit. We also looked at the positive and negative predictive values (PPV, NPV), as well as the false discovery rate (FDR) and false omission rate (FOR) for scales found to have increased odds of elevation in PNES patients. This was completed for the overall sample, as well as the sample stratified by sex. RESULTS: The odds of elevations related to somatic concerns, negative mood, and suicidal ideation in the PNES sample ranged from 2 to 5 times more likely. Female PNES patients had 3-6 times greater odds of such scale elevations, while male PNES patients had odds of 5-15 times more likely. PPV rates ranged from 53.66% to 84.62%, while NPV rates ranged from 47.52% to 90.91%. FDR across scales ranged from 15.38% to 50%, while the FOR ranged from 9.09% to 52.47%. CONCLUSIONS: Consistent with prior research, PNES patients have greater odds of MMPI-2-RF scale elevations, particularly related to somatic concerns and mood disturbance. Female PNES patients endorsed greater emotional distress, including endorsement of suicide related items. Elevations of these scales could aid in differentiating PNES from ES patients, although caution is warranted due to the possibility of both false positives and the incorrect omissions of PNES cases.