Adaptive functioning, most notably practical skills, are impacted in pediatric brain tumor survivors. This study aimed to examine the individual components of practical adaptive functions that are most impacted in pediatric brain tumor survivors, and to identify specific medical and socio-demographic factors that contribute to weaknesses in this domain.

The sample consisted of 117 pediatric brain tumor patients seen for a clinical neuropsychological evaluation. Inclusion criteria included participants <18 years at time of brain tumor diagnosis, and whose parents were administered the Adaptive Behavior Assessment System, Second (ABAS-II) or Third Edition (ABAS-3) as a measure of adaptive functioning. Medical and socio-demographic variables were gathered from the patient’s medical record. Medical variables examined were age at diagnosis, age at evaluation, time since diagnosis, tumor location (supratentorial or infratentorial), and history of treatment and associated complications as measured by the Neurologic Predictor Scale (NPS). Socio-demographic factors examined included sex, race, insurance type, parental education, and Area Deprivation Index (ADI) as a measure of neighborhood deprivation/access to community resources. One sample t-tests compared the brain tumor sample to population normative means. Correlations examined associations between practical skills and medical and socio-demographic variables. To determine predictors of practical skills, significant correlations were entered into separate linear regressions for each of the four practical subscales (Community Use, Home Living, Health & Safety, Self-Care).

Participants were diagnosed around 7 years and were approximately 5 years from diagnosis at the time of neuropsychological evaluation. Practical skills were clinically and statistically significantly below the normative mean (Standard Score=85.5, p<.001). Additionally, all practical subscales were statistically significantly below the normative mean (p<.001), with both Community Use (Scale Score=7.6, p<.001) and Home Living (Scaled Score=6.9, p<.001) being clinically significant. Community Use was positively correlated with age at diagnosis (r=.27, p=.004) and negatively correlated with Neurologic Predictor Scale (r=-.33, p<.001), time since diagnosis (r=-.24, p=.01), and ADI (r=-.23, p=.02). Health and Safety was positively correlated with age at diagnosis (r=.21, p=.024). Self-Care was positively correlated with age at diagnosis (r=.202, p=.029) and parental education (r=.203, p=.037); Home Living was not correlated with any of the variables examined. Predictors of Community Use included NPS score (p=.002); ADI approached significance (p=.07). Age at diagnosis predicted Health & Safety practical skills (p=.024), and parental education predicted Self-Care skills (p=.004).

Pediatric brain tumor survivors demonstrate clinically significant weakness in practical skills. While specific medical and socio-demographic factors contribute to lower practical adaptive functioning (e.g., younger age at diagnosis, higher NPS score suggestive of greater treatment burden, longer time since diagnosis, lower ADI score suggestive of greater neighborhood deprivation, and lower parental education), medical and socio-demographic factors do not equally impact practical adaptive functions, but rather individual factors predict specific practical skills. While there is appreciation for the contribution of medical factors in pediatric oncology, few studies have examined socio-demographic factors in this population. This study highlights the importance of considering the role of family and environmental factors on neuropsychological functioning in pediatric oncology in addition to medical factors.

Radiotherapy for pediatric brain tumor has been associated with late cognitive effects. Compared to conventional photon radiotherapy (XRT), proton radiotherapy (PRT) delivers less radiation to healthy brain tissue. PRT has been associated with improved long term cognitive outcomes compared to XRT. However, there is limited research comparing the effects of XRT and PRT on verbal memory outcomes.

Survivors of pediatric brain tumor treated with either XRT (n = 29) or PRT (n = 51) completed neuropsychological testing > 1 year following radiotherapy. XRT and PRT groups were similar with respect to sex, handedness, race, age at diagnosis, age at evaluation, tumor characteristics, and treatment history (i.e., craniospinal irradiation, craniotomy, shunting, chemotherapy, radiation dose). Verbal learning and memory were assessed using the age-appropriate version of the California Verbal Learning Test (CVLT-II/CVLT-C). Measures of intellectual functioning, executive functioning, attention and adaptive behavior were also collected. Performance on neuropsychological measures was compared between treatment groups (XRT vs. PRT) using analysis of covariance (ANCOVA). On the CVLT, each participant was classified as having an encoding deficit profile (i.e., impaired learning, recall, and recognition), retrieval deficit profile (i.e., impaired recall but intact recognition), intact profile, or other profile. Chi-squared tests of independence were used to compare the probability of each memory profile between treatment groups. Pearson correlation was used to examine associations between memory performance and strategy use, intellectual functioning, adaptive behavior, attention, and executive functioning.

Overall, patients receiving PRT demonstrated superior verbal learning (CVLT Trials 1-5; t(76) = 2.61, p = .011), recall (CVLT Long Delay Free; t(76) = 3.57, p = .001) and strategy use (CVLT Semantic Clustering; t(76) = 2.29, p = .025) compared to those treated with XRT. Intact performance was more likely in the PRT group than the XRT group (71% PRT, 38% XRT; X2 = 8.14, p = .004). Encoding and retrieval deficits were both more common in the XRT group, with encoding problems being most prevalent (Encoding Deficits: 31% XRT, 12% PRT, X2 = 4.51, p = .034; Retrieval Deficits: 17% XRT, 4% PRT, X2 = 4.11, p = .043). Across all participants, semantic clustering predicted better encoding (r = .28, p = .011) and retrieval (r = .26, p = .022). Better encoding predicted higher intellectual (r = .56, p < .001) and adaptive functioning (r = .30, p = .011), and fewer parent-reported concerns about day-today attention (r = -.36, p = .002), and cognitive regulation (r = -.35, p = .002).

Results suggest that PRT is associated with superior verbal memory outcomes compared to XRT, which may be driven by encoding skills and use of learning strategies. Moreover, encoding ability predicted general intellectual ability and day-to-day functioning. Future work may help to clarify underlying neural mechanisms associated with verbal memory decline following radiotherapy, which will better inform treatment approaches for survivors of pediatric brain tumor.

Cognitive difficulties among diffuse glioma survivors are common in survivorship due to cancer treatment effects (i.e., surgery, chemotherapy, and/or radiation therapy), which can diminish quality of life. Routine monitoring of cognitive symptoms in survivorship is recommended and can help address patient needs and inform clinical interventions (e.g., cognitive rehabilitation). While several patient-reported outcome (PRO) measures have been used in brain tumor populations, there has been few studies comparing the performance of these PROs in patients with diffuse glioma. In order to better understand the value of different PROs, we conducted preliminary analyses associating cognitive PROs with neuropsychological impairment in a well-characterized sample of patients with diffuse glioma.

23 glioma patients (mean aged 44.26 ± 12.24), six or more months after completing cancer treatment, underwent comprehensive psychosocial and neuropsychological assessments. The neuropsychological battery included the Hopkins Verbal Learning Test - Revised, Brief Visuospatial Memory Test - Revised, Wechsler Adult Intelligence Scale-IV tests of Coding and Digit Span, Trail-Making Test, Stroop Test, FAS, Animals, Boston Naming Test, and Rey-Osterrieth Complex Figure (copy). Completed cognitive PROs included the Functional Assessment of Cancer - Cognitive Function and Brain questionnaires (FACT-Cog; FACT-Br), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire for Brain Neoplasms (EORTC QLQ-BN20), and the Multidimensional Fatigue Symptom Inventory, short form (MFSI-SF) Mental subscale. Based on published norms, we divided the sample into cognitively impaired and non-impaired groups (two or more primary neuropsychological test scores <= -2 z-score). We compared PRO scores between impaired and non-impaired groups using Mann-Whitney U tests. Higher medians equate to better cognitive functioning for all PROs, except for the MSFI-SF.

We found significantly worse scores in the impaired group compared to non-impaired group on the FACT-Cog subscales of perceived cognitive ability (PCA), [Non-Impaired (Mdn = 21, n = 11), Impaired (Mdn = 10, n = 12), U = 22.5, z = -2.68, = 0.007], perceived cognitive impairment (PCI), [Non-Impaired (Mdn = 59, n = 11), Impaired (Mdn = 44, n = 12), U = 32.5, z = -2.06, p=0.039]. The impaired group also trended towards worse scores on the FACT-Br additional concerns subscale [Non-Impaired (Mdn = 79.5, n = 10), Impaired (Mdn = 61, n = 12), U = 32.5, z = -1.81, p=0.07]. Group differences were not observed on the MSFI-SF [Non-Impaired (Mdn = 5, n = 11), Impaired (Mdn = 7, n = 12), U = 40.5, z = -1.57, p=0.12], or EORTC Cognitive Functioning subscale [Non-Impaired (Mdn = 83.33, n = 10), Impaired (Mdn = 75, n = 12), U = 42, z = -1.23, p=0.218].

The preliminary findings suggest that the FACT-Cog, especially the PCA and PCI correspond with neuropsychological impairment among diffuse glioma survivors better than other cognitive PROs. The FACT-Br subscale was somewhat effective. The MFSI-SF Mental and EORTC Cognitive Functioning subscales did not correspond to impairment status. The FACT-Cog is a promising instrument and future work is needed to better determine relative utility of cognitive PROs in this population.

Treatment for pediatric brain tumors (PBTs) is associated with neurocognitive risk, including declines in IQ, executive function, and visual motor processing. Low grade tumors require less intensive treatment (i.e., focal radiotherapy (RT) or surgical resection alone), and have been associated with more favorable cognitive outcomes. However, these patients remain at risk of cognitive problems, which may present differently depending on tumor location. Executive functioning (EF), in particular, has been broadly associated with both frontal-subcortical networks (supratentorial) and the cerebellum (infratentorial). The current study examined intellectual functioning, executive functioning (set-shifting and inhibition), and visual motor skills in patients who were treated for low-grade tumors located in either the supratentorial or infratentorial region.

Participants were survivors (age 8-18) previously treated with focal proton RT or surgery alone for infratentorial (n=21) or supratentorial (n=34) low grade glioma (83.6%) or low grade glioneuronal tumors (16.4%). Survivors >2.5 years post-treatment completed cognitive testing (WISC-IV/WAIS-IV; D-KEFS Verbal Fluency (VF), Color-Word Interference (CW), Trail Making Test (TM); Beery Visual-Motor Integration). We compared outcomes between infratentorial and supratentorial groups using analysis of covariance (ANCOVA). Demographic and clinical variables were compared using Welch’s t-tests. ANCOVAs were adjusted for age at evaluation, age at treatment, and history of posterior fossa syndrome due to significant or marginally significant differences between groups.

Tumor groups did not significantly differ with respect to sex (49.0% male), length of follow-up (M 4.4 years), or treatment type (74.5% surgery alone, 25.5% proton RT). Marginally significant group differences were found for age at evaluation (infratentorial M = 12.4y, supratentorial M = 14.1y, p = .054) and age at treatment (infratentorial M = 7.9y, supratentorial M = 9.7y, p =.074). Posterior fossa syndrome only occurred with infratentorial tumors (n=5, p = .003). Adjusting for covariates, the supratentorial group exhibited significantly superior performance on a measure of inhibition and set-shifting (CW Switching Time (t(32) = -2.05, p=.048, n2 =.11). There was a marginal group difference in the same direction on CW Inhibition Time (t(32 = -1.77, p = .086, n2 =.08). On the other hand, the supratentorial group showed significantly lower working memory than the infratentorial group (t(50) = 2.45, p = .018, n2 = .11), and trends toward lower verbal reasoning (t(50)=1.96, p = .056, n2 = .07) and full-scale IQ (t(50)=1.73, p = .090, n2 = .055). No other group differences were identified across intellectual, EF, and visualmotor measures.

Infratentorial tumor location was associated with weaker switching and inhibition performance, while supratentorial tumor location was associated with lower performance on intellectual measures, particularly working memory. These findings suggest that even with relatively conservative treatment (i.e., focal proton RT or surgery alone), there remains neurocognitive risk in children treated for low-grade brain tumors. Moreover, tumor location may predict distinct patterns of long-term neurocognitive outcomes, depending on which brain networks are involved.

The purpose of this study using archival data was to examine processing speed (PS) and its relation with academic fluencies in children who were diagnosed with, and treated with chemotherapy for, acute lymphoblastic leukemia (ALL) before vs. after five years of age. Chemotherapy is the first-line treatment for childhood leukemias, and the impact of cancer treatment on academic and global functioning may include a steady decline in functions over time (Baron & Rey-Casserly, 2013). Specifically, this research initiative examined age and gender factors in PS and academic fluencies in this population.

Sixty-eight participants (39 M, 29 F; mean age 10.6 years) diagnosed with ALL and who were previously treated with chemotherapy were included. Thirty-seven participants (23 M, 14 F) were <5 years of age at the time of diagnosis and onset of chemotherapy, while 31 participants (16M, 15 F) were >5 years of age at diagnosis and treatment. Participants ranged in age from 6 to 17 years at the time of their neuropsychological evaluation. Participants were given the WISC-V (PS subtests) and WJ-IV academic fluencies (math and reading). To evaluate research questions and hypotheses, correlational tests, independent samples t-tests, and analyses of variance (ANOVA) were used. Results at the p< .05 level are reported.

There were significant correlations between PS and WJ math fluency (r=.510) and reading fluency (r=.392). Independent samples t-test analyses revealed that children who scored below 85 (standard score) on PS composite score demonstrated poorer performance on WJ math fluency (t(60)=-3.971, p=.000, d=1.065) and reading fluency (t(56)=-3.041, p=.004, d=0.896) compared to children whose PS scores were > 85. For children whose PS scores were <85, mean scores were in the low average range for WJ-IV math fluency (M=81.05) and reading fluency (M=84.50). No significant differences were found for age or gender in relation to PS and academic fluencies.

Findings are important in highlighting the need for school accommodations in pediatric survivors of ALL. Processing speed is one of the most vulnerable functions impacted by cancer therapies and was positively correlated with reading and math fluencies in this study. Mean scores for math and reading fluencies were low average for age. In terms of academic accommodations, due to the slow processing speed of these boys and girls, regardless of their age at diagnosis and onset of chemotherapy, the provision for extra time for ALL survivors is recommended to ensure they are given the opportunity to maximize their learning potential and demonstrate their true academic abilities. Parents are encouraged to practice basic fluencies at home as early as possible. Inhospital and home-bound schooling supports are recommended to maintain educational progress. For children at higher risk for late effects and neurocognitive decline, rehabilitation similar to that which TBI survivors receive can be effective, as well. Future prospective research, including longitudinal tracking, with more homogeneous samples of pediatric survivors of ALL is expected to extend and refine findings of the present study.

The goal of the current study is to compare QoL between tumor grade levels (i.e., low vs high) as well as the relationship between QoL, cognition, and tumor grade.

Participants were 156 individuals diagnosed with a brain tumor who completed neuropsychological evaluation within an interdisciplinary brain tumor clinic (mean age=51.67; SD=15.0; mean education=13.98; SD=2.6; 59% male). Independent samples T-Test was utilized to review participants’ reported overall quality of life (QoL) on the FACT-Br in relation to tumor grade level (i.e., high vs low). Linear regression analysis was utilized to determine which cognitive variable may be most predictive of QoL.

Results of the Independent T-test demonstrated that low and high tumor grade level groups did not significantly differ in total or individual sub-domain QoL. With regard to the regression analysis, cognitive variables as measured by TMT B, HVLT delayed recall, and FAS accounted for significant variance in quality of life in both low grade and high grade tumor groups (low tumor grade level effect size R2 =0.21; high tumor grade level effect size R2 = 0.19). However, TMT B emerged as a significant predictor of QoL in only the low grade group, while cognitive performance within these same tasks did not significantly predict QoL for the high tumor grade level group.

Our findings did not significantly differ in the overall impact tumor grade level (i.e., low vs., high) has on QoL. Notably, cognitive performance on TMT B significantly predicts QoL for the low but not high tumor grade level group.

This study examines the clinical validity of the NIH Toolbox Cognition Battery measures in patients with oncological diagnoses and tumor predisposition syndromes, including Neurofibromatosis, Type 1 (NF1).

Participants included 158 patients (61% male, 67% White) ages 3 to 25 years (M = 8.38, SD = 4.32) who underwent neuropsychological evaluation between 2019 and 2022. Patients with brain tumors (n = 50) and leukemias (n = 49) accounted for 2/3 of the sample. The remainder had solid tumors, lymphomas, or cancer predisposition syndrome. Forty-eight had a diagnosis of NF1. Performance-based measures of attention, executive functioning, and processing speed were administered as part of neuropsychological evaluations. Patients were administered between 1 to 4 NIH Toolbox Cognition measures, including Flanker Inhibitory Control and Attention Test (Flanker), Dimensional Change Card Sort Test (DCCS), Pattern Comparison Processing Speed Test (PCCS), and List Sorting Test. Parent-reported measures of attention and EF were also obtained. Z-scores were used to compare performance across measures that assessed equivalent constructs. The rates of weak performance (>1 SD below the mean) using Toolbox measures were compared to rates of weak performance on traditional neuropsychological measures (e.g., Digit Span), and rates of functional impairment (e.g., parent-reported concerns, ADHD diagnosis).

FSIQ, Coding, and NEPSY Inhibition correlated with all 4 Toolbox measures, while Digit Span correlated with List Sorting, DCCS, and Flanker. DCCS and PCCS correlated with verbal fluency measures. NF1 patients scored lower than non-NF1 patients on Flanker, F(1,126) = 13.01, p<.001 and DCCS, F(1,150) = 6.85, p = .01. Toolbox performance did not differ significantly by age group. Rates of identified weakness were relatively similar on Toolbox measures, some traditional measures, and parent-reported attention problems. In identifying those with and without weakness, the agreement between Flanker and other measures ranged from 52% (Auditory Attention) to 66% (Coding). Agreement between DCCS and traditional measures ranged from 47% (Letter Fluency) to 80% (Switching). For PCCS, concordance ranged from 45% (Semantic Fluency) to 69% (Switching). List Sorting had 80% agreement with Digit Span and Coding.

List Sorting had the highest agreement with parent-reported attention problems (76%), EF problems (72%), and ADHD diagnosis (79%). There was relatively high concurrence between DCCS and ADHD diagnosis (69%) and parent-reported attention problems (60%) and EF problems (65%) and between Flanker and ADHD diagnosis (67%). PCCS had less agreement with functional outcomes, ranging from 49% for EF problems to 58% for attention problems and ADHD diagnosis. In comparison, Digit Span had 64% agreement for EF problems, 70% for attention problems, and 73% for ADHD diagnosis.

The NIH Toolbox Cognition Battery can be used to identify neurocognitive weaknesses in pediatric oncology patients and provide clinically meaningful data. Evaluation of the Toolbox measures’ sensitivity to change over time is warranted, as monitoring the progression of cognitive late effects is particularly salient in cancer survivorship.

Children with pediatric brain tumors (PBT) are at increased risk of psychosocial challenges (e.g., emotional distress, social difficulties), which in turn can result in functional impairment, or problems engaging appropriately across settings. These concerns have been shown to be especially pronounced in patients with lower socioeconomic status (SES), which tends to be overrepresented among ethnic minorities, such as Latino populations. On the other hand, resilience (the ability to utilize resources to alleviate stress and overcome adversity) can act as a protective factor against functional impairment. While resilience has been found to be lower among Latino survivors of pediatric cancer, little is known about the potential role of resilience in mitigating functional impairment among Latino patients with PBT. The authors hypothesized poorer resilience and increased functional impairment among Latino patients with PBT compared to normative expectations, in an attempt to explore need for additional support within this population.

42 Latino patients with PBT ages 2-20 (x=11.08 years, SD=5.24) completed neuropsychological evaluation between 2018 and 2022. The sample was split relatively equally in terms of sex (47.6% male, 52.4% female), tumor location (45.2% infratentorial, 54.8% supratentorial), and household language (47.6% predominantly English, 52.4% predominantly Spanish). Outcome variables included Resiliency and Functional Impairment content scales from the Behavior Assessment Scale for Children – Third Edition: Parent Rating Scales (BASC-3: PRS). Standardized T-scores (x=50; SD=10) were derived using age-appropriate normative data, with higher T-scores indicating better resiliency, yet poorer functional impairment. Median household income for specific neighborhoods was used as a proxy for SES.

The sample as a whole did not deviate from age expectations in terms of resiliency [t(41)=-.469, p=.642] or functional impairment [t(38)=.118, p=.907]. However, when separated by household language, participants from English speaking households demonstrated lower resiliency and increased functional impairment as compared to both normative expectations [t(19)=-2.748, p=.006; t(18)=1.882, p=.038, respectively] and participants from Spanish speaking households [t(40)=-3.327, p=.002; t(37)=2.717, p=.010, respectively]. In contrast, participants from Spanish speaking households performed similarly to same-aged peers in terms of both resiliency [t(21)=1.931, p=.067] and functional impairment [t(19)=-1.969, p=.064]. Furthermore, household language predicted both resiliency [F(2, 39)=8.639, p=.0008] and functional impairment [F(2, 36)=6.203, p=.005] above and beyond SES, explaining an additional 29.4% (p=.0002) and 24.3% (p=.002) of the variation in these variables, respectively.

Latino patients with PBT from Spanish speaking households had better reported resiliency and lower functional impairment than their counterparts from English speaking households. Given the subjective nature of parent reported outcomes and the importance of appropriately supporting patients and families from underserved populations, the roles of culturally-ingrained protective factors and cultural/linguistic differences in perceiving or articulating distress need further exploration. Future research, including comparison of parent report with objective measurement of impairment, is needed to better understand relationships between home language and these important variables. Additionally, examination of diagnostic and treatment-related factors will be beneficial to determine the best approaches to interventions and resources within this population.

Cognitive changes following adjuvant treatment for breast cancer (BC) are well documented particularly following chemotherapy. However, limited studies have examined cognitive and/or language functions in chemotherapy-naive women with BC taking tamoxifen (TAM). While there is some compelling evidence TAM affects cognitive and language domains, language has not been studied beyond semantics (i.e., content of language), which is just one aspect of language. Using ambulatory cognitive assessment, we investigated the trajectory of cognitive and language changes during early period of adjuvant endocrine treatment (tamoxifen) in women with BC at two time periods (pre-treatment and two months after treatment begins).

Four women with BC (mean age = 62.25 years, SD = 8.38) and 18 cognitively healthy age-matched controls (mean age = 59.77, SD = 7.45) completed 3 cognitive tasks using smartphones, during a short time period (5 days) and repeated at two time periods. Symbol search, dot memory and color dots tasks were used to measure the cognitive constructs - processing speed and working memory. Response times were recorded in milliseconds. To determine language ability, language samples were collected at two time periods, where the participants described two stories from two wordless picture books and samples were assessed using core lexicon analyses.

Wilcoxon-signed rank test was computed to identify cognitive and linguistic changes during early period of TAM administration in women with BC at two time periods. No significant within group or between group differences were seen on the cognitive and language tasks at the two time periods, however, a trend for decline in performance was seen in some BC participants across different tasks.

This is the first study to our knowledge to use ambulatory cognitive assessment method and study discourse-level language function during this early period (pre-treatment and 2 months post-TAM). Findings from the current study advance our understanding of trajectories of cognition and language changes during the initial course of adjuvant endocrine treatment for women with BC with ER+ tumors. Using a measurement-burst design and ambulatory cognitive assessment, we were able to apply better precision measurement to identify distinct cognitive constructs affected by adjuvant endocrine treatment. In addition, insight into changes in discourse ability are impactful for numerous reasons: (1) better understanding of how adjuvant endocrine therapy impacts communication and (2) discernment into language domains that may require early behavioral intervention.

Executive functioning (EF) and socioeconomic status (SES) are associated with functional outcomes (adaptive functioning and academic achievement) in healthy controls and pediatric populations with executive dysfunction. However, these relationships have yet to be investigated in survivors of childhood acute lymphoblastic leukemia (ALL), a population with EF impairment resulting from disease and treatment characteristics. The objective of this study was to examine the associations of functional outcomes with EF and SES (neighborhood-specific variables and academic support) in survivors of childhood ALL.

Forty-four participants (38.6% female, 72.7% non-Hispanic White, ages 6-17) previously diagnosed with low-risk or standard-risk pre-B cell ALL and treated with chemotherapy-only were included. Participants were evaluated on performance-based measures of EF (cognitive flexibility, verbal fluency, working memory, and processing speed) and academic achievement (word reading and math calculation), and parent-ratings of EF and adaptive functioning. All measures were expressed as T-scores with lower scores indicating better performance. Neighborhood-specific variables were based on participants’ zip codes and census block group, and included area deprivation index (ADI) and child opportunity index (COI). Lower ADI and COI indicate lesser deprivation and greater opportunity. Individualized education plan (IEP) status was used as a proxy of academic support, coded dichotomously as with or without IEP. Percentages of participants showing impairments in functional outcomes were calculated using a cutoff of > 1 SD above the normative mean. Partial correlations were conducted while controlling for age at evaluation, age at diagnosis, sex, and verbal IQ, to examine whether participants with poorer performance-based and parent-rated EF would show reduced functional outcomes. Multiple regression analyses were conducted to evaluate whether neighborhood-specific variables and IEP status would predict functional outcomes while controlling for covariates.

Compared to population norms, survivors of childhood ALL showed worse functional outcomes. Within adaptive functioning, 45.5% of participants showed impairment in activities of daily living and leadership. Adaptive functioning was significantly positively correlated with parent-rated, but not performance-based, EF (r=0.694, p<0.001). Compared to female survivors, male survivors were at increased risk for adaptive functioning difficulties (r=-0.401, p<0.05). Impairments for word reading and math calculation were 25% and 41.7%, respectively. Greater math calculation was associated with better verbal fluency (r=0.378, p<0.05) and processing speed (r=0.439, p<0.05). Older participants at evaluation (/3=-0.580, p<0.001) and those without IEP support (ß=0.465, p<0.05) showed better word reading. Lower ADI predicted better verbal fluency (ß=0.282, p=0.041), however, neighborhood-specific variables were not associated with functional outcomes.

Prior findings indicate that performance-based measures and parent-ratings assess different constructs of EF. Thus, adaptive functioning may relate more to the behavioral construct of EF than its cognitive construct. Current findings also suggest that male survivors are at increased risk for reduced adaptive functioning, consistent with recent reports that male survivors of ALL are at greater risk for specific neurocognitive outcomes. Overall, functional outcomes may be more strongly related to EF than neighborhood-specific variables. Long-term goals include early screening of adaptive and academic difficulties, targeted intervention, and neuropsychological monitoring to support pediatric survivors’ neurocognitive and psychosocial development.

Hippocampal pathology is a consistent feature in persons with temporal lobe epilepsy (TLE) and a strong biomarker of memory impairment. Histopathological studies have identified selective patterns of cell loss across hippocampal subfields in TLE, the most common being cellular loss in the cornu ammonis 1 (CA1) and dentage gyrus (DG). Structural neuroimaging provides a non-invasive method to understand hippocampal pathology, but traditionally only at a whole-hippocampal level. However, recent methodological advances have enabled the non-invasive quantification of subfield pathology in patients, enabling potential integration into clinical workflow. In this study, we characterize patterns of hippocampal subfield atrophy in patients with TLE and examine the associations between subfield atrophy and clinical characteristics.

High-resolution T2 and T1-weighted MRI were collected from 31 participants (14 left TLE; 6 right TLE; 11 healthy controls [HC], aged 18-61 years). Reconstructions of hippocampal subfields and estimates of their volumes were derived using the Automated Segmentation of Hippocampal Subfields (ASHS) pipeline. Total hippocampal volume was calculated by combining estimates of the subfields CA1-3, DG, and subiculum. To control for variations in head size, all volume estimates were divided by estimates of total brain volume. To assess disease effects on hippocampal atrophy, hippocampi were recoded as either ipsilateral or contralateral to the side of seizure focus. Two sample t-tests at a whole-hippocampus level were used to test for ipsilateral and contralateral volume loss in patients relative to HC. To assess whether we replicated the selective histopathological patterns of subfield atrophy, we carried out mixed-effects ANOVA, coding for an interaction between diagnostic group and hippocampal subfield. Finally, to assess effects of disease load, non-parametric correlations were performed between subfield volume and age of first seizure and duration of illness.

Patients had significantly smaller total ipsilateral hippocampal volume compared with HC (d=1.23, p<.005). Contralateral hippocampus did not significantly differ between TLE and HC. Examining individual subfields for the ipsilateral hemisphere revealed significant main-effects for group (F(1, 29)=8.2, p<0.01), subfields (F(4, 115)=550.5, p<0.005), and their interaction (F(4, 115)=8.1, p<0.001). Post-hoc tests revealed that TLE had significantly smaller volume in the ipsilateral CA1 (d=-2.0, p<0.001) and DG (d = -1.4, p<0.005). Longer duration of illness was associated with smaller volume of ipsilateral CA2 (p=-0.492, p<0.05) and larger volume of contralateral whole-hippocampus (p=0.689, p<0.001), CA1 (p=0.614, p < 0.005), and DG (p=0.450, p<0.05).

Histopathological characterization after surgery has revealed important associations between hippocampal subfield cell loss and memory impairments in patients with TLE. Here we demonstrate that non-invasive neuroimaging can detect a pattern of subfield atrophy in TLE (i.e., CA1/DG) that matches the most common form of histopathologically-observed hippocampal sclerosis in TLE (HS Type 1) and has been linked directly to both verbal and visuospatial memory impairment. Finally, we found evidence that longer disease duration is associated with larger contralateral hippocampal volume, driven by increases in CA1 and DG. This may reflect subfield-specific functional reorganization to the unaffected brain tissue, a compensatory effect which may have important implications for patient function and successful treatment outcomes.

Children with epilepsy are at greater risk of lower academic achievement than their typically developing peers (Reilly and Neville, 2015). Demographic, social, and neuropsychological factors, such as executive functioning (EF), mediate this relation. While research emphasizes the importance of EF skills for academic achievement among typically developing children (e.g., Best et al., 2011; Spiegel et al., 2021) less is known among children with epilepsy (Ng et al., 2020). The purpose of this study is to examine the influence of EF skills on academic achievement in a nationwide sample of children with epilepsy.

Participants included 427 children with epilepsy (52% male; MAge= 10.71), enrolled in the Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Database who had been referred for surgery and underwent neuropsychological testing. Academic achievement was assessed by performance measures (word reading, reading comprehension, spelling, and calculation and word-based mathematics) and parent-rating measures (Adaptive Behavior Assessment System (ABAS) Functional Academics and Child Behavior Checklist (CBCL) School Performance). EF was assessed by verbal fluency measures, sequencing, and planning measures from the Delis Kaplan Executive Function System (DKEFS), NEPSY, and Tower of London test. Rating-based measures of EF included the 'Attention Problems’ subscale from the CBCL and 'Cognitive Regulation’ index from the Behavior Rating Inventory of Executive Function (BRIEF-2). Partial correlations assessed associations between EF predictors and academic achievement, controlling for fullscale IQ (FSIQ; A composite across intelligence tests). Significant predictors of each academic skill or rating were entered into a two-step regression that included FSIQ, demographics, and seizure variables (age of onset, current medications) in the first step with EF predictors in the second step.

Although zero-order correlations were significant between EF predictors and academic achievement (.29 < r’s < .63 for performance; -.63 < r’s < -.50 for rating measures), partial correlations controlling for FSIQ showed fewer significant relations. For performance-based EF, only letter fluency (DKEFS Letter Fluency) and cognitive flexibility (DKEFS Trails Condition 4) demonstrated significant associations with performance-based academic achievement (r’s > .29). Regression models for performance-based academic achievement indicated that letter fluency (ß = .22, p = .017) and CBCL attention problems (ß = -.21, p =.002) were significant predictors of sight-word reading. Only letter fluency (ß = .23, p =.006) was significant for math calculation. CBCL Attention Problems were a significant predictor of spelling performance (ß = -.21, p = .009) and reading comprehension (ß = -.18, p =.039). CBCL Attention Problems (ß = -.38, p <.001 for ABAS; ß = -.34, p =.002 for CBCL School) and BRIEF-2 Cognitive Regulation difficulties (ß = -.46, p < .001 for ABAS; ß = -.46, p =.013 for CBCL School) were significant predictors of parent-rated ABAS Functional Academics and CBCL School Performance.

Among a national pediatric epilepsy dataset, performance-based and ratings-based measures of EF predicted performance academic achievement, whereas only ratings-based EF predicted parent-rated academic achievement, due at least in part to shared method variance. These findings suggest that interventions that increase cognitive regulation, reduce symptoms of attention dysfunction, and promote self-generative, flexible thinking, may promote academic achievement among children with epilepsy.

The COVID-19 pandemic significantly disrupted schools and learning formats. Children with epilepsy are at-risk for generalized academic difficulties. We investigated the potential impact of COVID-19 on learning in those with epilepsy by comparing achievement on well-established academic measures among school-age children with epilepsy referred prior to the COVID-19 pandemic and those referred during the COVID-19 pandemic.

This study included 466 children [52% male, predominately White (76%), MAge=10.75 years] enrolled in the Pediatric Epilepsy Research Consortium Epilepsy (PERC) Surgery database project who were referred for surgery and seen for neuropsychological testing. Patients were divided into two groups based on a proxy measure of pandemic timing completed by PERC research staff at each site (i.e., “were there any changes to typical in-person administration [of the evaluation] due to COVID?”). 31% of the sample (N = 144) were identified as having testing during the pandemic (i.e., “yes” response), while 69% were identified as having testing done pre-pandemic (i.e., “no” response). Of the 31% who answered yes, 99% of administration changes pertained to in-person testing or other changes, with 1% indicating remote testing. Academic achievement was assessed by performance measures (i.e., word reading, reading comprehension, spelling, math calculations, and math word problems) across several different tests. T-tests compared the two groups on each academic domain. Subsequent analyses examined potential differences in academic achievement among age cohorts that approximately matched grade level [i.e., grade school (ages 5-10), middle school (ages 11-14), and high school (ages 15-18)].

No significant differences were found between children who underwent an evaluation before the pandemic compared to those assessed during the pandemic based on age norms across academic achievement subtests (all p’s > .34). Similarly, there were no significant differences among age cohorts. The average performance for each age cohort generally fell in the low average range across academic skills. Performance inconsistently varied between age cohorts. The youngest cohort (ages 5-10) scored lower than the other cohorts for sight-word reading, whereas this cohort scored higher than the middle cohort (ages 11-14) for math word problems and reading comprehension. There were no significant differences between the two pandemic groups on demographic variables, intellectual functioning, or epilepsy variables (i.e., age of onset, number of seizure medications, seizure frequency).

Academic functioning was generally equivalent between children with epilepsy who underwent academic testing as part of a pre-surgical evaluation prior to the pandemic compared to those who received testing during the pandemic. Additionally, academic functioning did not significantly differ between age cohorts. Children with epilepsy may have entered the pandemic with effective academic supports and/or were accustomed to school disruptions given their seizure history. Replication is needed as findings are based on a proxy measure of pandemic timing and the extent to which children experienced in-person, remote, and hybrid learning is unknown. Children tested a year into the pandemic, after receiving instruction through varying educational methods, may score differently than those tested earlier. Future research can address these gaps. Although it is encouraging that academic functioning was not disproportionately impacted during the pandemic in this sample, children with epilepsy are at-risk for generalized academic difficulties and continued monitoring of academic functioning is necessary.

Neuropsychological assessment is an essential part of presurgical evaluation for epilepsy patients with refractory temporal lobe epilepsy. Evaluations assist in localizing and lateralizing epileptogenic focal points and identifying possible risks for cognitive decline following surgery. Researchers and clinicians consistently find that verbal memory dysfunction is an accurate indicator of left temporal lobe epilepsy (TLE) through verbal measures such as the CVLT-II. Although visual memory structures are assumed to be in the right (nondominant) hemisphere, visual memory assessments have not been reliable in identifying right TLE. It is hypothesized that assessments to test visual memory are confounded by verbal cueing to assist in visual learning. To account for this, researchers have identified that comparing verbal and visual score asymmetries does accurately differentiate left and right TLE patients. This study aimed to determine if verbalvisual asymmetry using the CVLT-II and BVMT-R accurately identifies left and right TLE relative weaknesses potentially associated with epileptogenic regions.

As part of a pre-surgical neuropsychological evaluation, 37 well-characterized medically refractory TLE patients (18 right TLE; 19 left TLE) were administered the Brief Visuospatial Memory Test-Revised to evaluate visuospatial memory and the CVLT-II to evaluate verbal memory. A multivariate analysis of variance was used to compare RTLE and LTLE group performances on BVMT-R delay recall subscales, using T-scores. Then memory asymmetry scores were calculated by converting CVLT-II verbal delay memory scores to T-scores and subtracting BVMT-R delayed recall T-score from the verbal memory T-score. An independent samples t-test was used to compare asymmetry scores between the groups.

There were no significant differences between patients with RTLE and LTLE for BVMT-R Delay [F(2,34) = 0.11, p = .895]. There was not a significant difference when accounting for verbal-visual asymmetry (t (35) = 0.422, p = 0.675, d = 12.566) between left (M = -2.42, SD = 13.82) and right side (M = -4.17, SD = 11.09).

The BVMT-R did not identify nondominant hemisphere dysfunction in this sample of 18 right TLE patients. Because visual memory performance did not inform lateralization, we investigated the usefulness of memory asymmetry. Inconsistent with our hypothesis, verbal-visual memory asymmetry scores did not differentiate RTLE from LTLE in this sample. These findings add to existing findings that the BVMT-R may not be able to identify visuospatial memory dysfunction in epilepsy. Additionally, these data indicate the inability to assess for visuospatial memory even when accounting for verbal abilities in epilepsy patients. Future research should consider alternate visuospatial measures for the evaluation of epilepsy patients.

Epilepsy is the third most common neurological disorder among older adults, and as adults are living longer, the incidence of epilepsy is increasing (Kun Lee, 2019). The purpose of this study is to examine 1. differences in quality of life (QOL) between older and younger adults with medically intractable epilepsy and 2. the impact of seizure frequency, seizure duration, depression, sex, and marital status on QOL. Given differences in the prevalence rates of depression between men and women and importance of depression in QOL, we predicted that sex and marital status would moderate the effect of depression on total QOL (TQOL).

Hypothesis I: Compared to younger adults, older adults with epilepsy will report lower TQOL scores and lower scores on subscales measuring energy/fatigue, cognition, and medication effects. Hypothesis II: Seizure variables and depression will significantly account for TQOL scores in both groups (younger and older) above demographic variables (sex, marital status, and education). Hypothesis III: Sex will moderate the effect of depression in both groups and marital status will moderate the effect of depression only in the older adults.

Participants were 607 adults (> 18 years old) who were prospective candidates for epilepsy surgery and underwent a comprehensive neuropsychological evaluation including QOL assessment using the Quality of Life in Epilepsy Scale-31 (QOLIE-31). Individuals were grouped by older (> 50 years old; N = 122) and younger adults (< 50 years old; N = 485). Hierarchical regression was used to examine the proposed associations.

Hypothesis I: In contrast to our hypothesis, a one-way ANOVA did not reveal significant differences between the older and younger groups on the QOL subscales, TQOL, or depression.

Hypothesis II: For older adults, longer seizure duration was associated with better TQOL; bivariate correlations showed no evidence of statistical suppression. Higher depression scores were associated with worse TQOL. Overall, the model accounted for 39.6% of variance among older adults. For younger adults, only depression was a significant predictor of TQOL wherein higher depression scores were associated with worse TQOL. Overall, the model accounted for 36.1% of the variance among younger adults. Hypothesis III: There was no moderation between depression and marital status in older or younger adults (b = -.009, p > .05). There was multicollinearity evidenced by VIF (variance inflation factor) greater than 10, so the associations between depression and sex could not be examined.

Overall, there were no significant differences between QOL in younger versus older adults. Greater depression symptoms were associated with lower TQOL in both groups. Longer seizure duration was a significant predictor of better TQOL in older adults only, perhaps indicating better adjustment to having a seizure disorder with longer duration of epilepsy. Lastly, marital status did not moderate the effects of depression on TQOL and the moderating effects of sex on TQOL could not be assessed due to multicollinearity. Study limitations include dichotomizing the sample into these particular age groups and the heterogeneity of seizure types.

Patients with temporal lobe epilepsy (TLE) commonly show memory deficits on neuropsychological tests. The BVMT-R is a widely used test of visual learning and memory that involves accurately reproducing an array of figures in the correct special location. The present study examined performance processes of visual memory in presurgical patients with TLE, including item (i.e., accuracy) and associative memory (i.e., location), which have been shown to be dissociable in studies of visual memory in other neurologic populations.

Participants included nine patients with left TLE (67% female; 67% left-handed; mean age = 46.15 years, range = 24-55; mean education = 14.8 years, range = 9-18) and six patients with right TLE (17% female; 33% left-handed; mean age = 57.64 years, range = 22-62; mean education = 15.52 years, range 11-18). Mean duration of epilepsy was 19 years. Participants had an average of two failed anti-seizure medications prior to surgery. TLE groups were compared to 22 healthy controls (36% female; 14% left-handed; mean age = 33.68 years, range = 2253; mean education = 17.66 years, range = 1620). All participants completed comprehensive neuropsychological testing at a large Northeastern medical center. The BVMT-R was scored using standard and novel scoring paradigms. All data were retrospectively reviewed from archival datasets.

MANCOVA results indicated a significant multivariate main effect for group membership and standard BVMT-R scoring after controlling for level of education, Wilks’ A = 0.59, F(4, 64) = 4.91, p = .002. The multivariate partial eta squared (np2) of .58 indicated a strong relationship between group membership and both immediate and delayed recall, with the control group performing better overall. The TLE groups did not perform significantly different from each other. A significant multivariate main effect for group and novel BVMT-R scoring was found (also controlling for education), Wilks’ A = 0.42, F(8, 58) = 3.97, p = .001. Overall, the control group demonstrated better item learning with no significant difference between TLE groups observed. Both the control (M = (16.5, SD = 2.04) and left TLE (M = 12.33, SD = 4.03) showed stronger associative learning compared to the right TLE group (M = 10.2, SD = 4.27). For item and location delayed recall, controls (M = 4.82, SD = 1.62) had more accurate recall compared to left TLE (M = 1.56, SD = 2.04) with a trend toward better performance compared to the right TLE patients (M = 2.6, SD = 1.82); the TLE groups performed similarly. No difference was observed for associative delayed recall between the three groups.

Patients with right TLE showed worse associative learning compared to left TLE, while performance was generally comparable to their right TLE counterparts on other novel BVMT-R scoring paradigms. Unsurprisingly, patients with TLE performed worse on BVMT-R using standard scoring procedures, though no lateralizing effect was observed. While these findings suggest that associative visual learning weakness may be characteristic of right TLE, findings should be interpreted cautiously the given small sample size and demographic considerations (i.e., uneven gender distribution, lack of data on ethnicity/race).

Anterior temporal lobectomy is a common surgical approach for medication-resistant temporal lobe epilepsy (TLE). Prior studies have shown inconsistent findings regarding the utility of presurgical intracarotid sodium amobarbital testing (IAT; also known as Wada test) and neuroimaging in predicting postoperative seizure control. In the present study, we evaluated the predictive utility of IAT, as well as structural magnetic resonance imaging (MRI) and positron emission tomography (PET), on long-term (3-years) seizure outcome following surgery for TLE.

Patients consisted of 107 adults (mean age=38.6, SD=12.2; mean education=13.3 years, SD=2.0; female=47.7%; White=100%) with TLE (mean epilepsy duration =23.0 years, SD=15.7; left TLE surgery=50.5%). We examined whether demographic, clinical (side of resection, resection type [selective vs. non-selective], hemisphere of language dominance, epilepsy duration), and presurgical studies (normal vs. abnormal MRI, normal vs. abnormal PET, correctly lateralizing vs. incorrectly lateralizing IAT) were associated with absolute (cross-sectional) seizure outcome (i.e., freedom vs. recurrence) with a series of chi-squared and t-tests. Additionally, we determined whether presurgical evaluations predicted time to seizure recurrence (longitudinal outcome) over a three-year period with univariate Cox regression models, and we compared survival curves with Mantel-Cox (log rank) tests.

Demographic and clinical variables (including type [selective vs. whole lobectomy] and side of resection) were not associated with seizure outcome. No associations were found among the presurgical variables. Presurgical MRI was not associated with cross-sectional (OR=1.5, p=.557, 95% CI=0.4-5.7) or longitudinal (HR=1.2, p=.641, 95% CI=0.4-3.9) seizure outcome. Normal PET scan (OR= 4.8, p=.045, 95% CI=1.0-24.3) and IAT incorrectly lateralizing to seizure focus (OR=3.9, p=.018, 95% CI=1.2-12.9) were associated with higher odds of seizure recurrence. Furthermore, normal PET scan (HR=3.6, p=.028, 95% CI =1.0-13.5) and incorrectly lateralized IAT (HR= 2.8, p=.012, 95% CI=1.2-7.0) were presurgical predictors of earlier seizure recurrence within three years of TLE surgery. Log rank tests indicated that survival functions were significantly different between patients with normal vs. abnormal PET and incorrectly vs. correctly lateralizing IAT such that these had seizure relapse five and seven months earlier on average (respectively).

Presurgical normal PET scan and incorrectly lateralizing IAT were associated with increased risk of post-surgical seizure recurrence and shorter time-to-seizure relapse.

In the US, >20% of individuals aged 5 years and older speak a language other than English at home, with rates of bi- and multilingualism increasing. Providing linguistically- and culturally- competent care to increasingly diverse populations is a necessary task for neuropsychologists. The need for close attention to bilingualism is even more glaring in the context of neurosurgical interventions, such as in intractable epilepsy. Pre-surgical epilepsy evaluations serve as a baseline for post-surgical change, inform lateralization and localization, and help determine cognitive risks associated with surgery. The importance of evaluating bilingual status and assessing cognitive abilities in both languages, if needed, in presurgical epilepsy evaluations is examined. We present the neuropsychological profile of a 10-year-old bilingual male with intractable epilepsy participating in a pre-surgical epilepsy evaluation.

This right-handed male is a sequential language learner, exposed to Spanish at birth and English when he began kindergarten. His parent reported he was primarily English speaking. Developmental milestones were met within expected timeframes. Seizures began at age 5. He is prescribed Vimpat and Lamictal. vEEG during admission revealed right temporal-onset seizures. Neuropsychological assessment was conducted in English based on parent report; however, expressive language testing revealed significantly higher performance in Spanish (average) compared to English (exceptionally low). Subsequently, a bilingual provider was consulted, and supplemental Spanish verbal reasoning and verbal memory measures were administered.

The patient’s neuropsychological profile captured a significant difference between English and Spanish verbal abilities. WISC-V Similarities scaled scores (ss) were 5 and 11 in English and Spanish, respectively. Vocabulary scaled scores were 8 and 15 in English and Spanish, respectively. Regarding verbal memory, list learning was below average in English (ss = 5), but low average in Spanish (ss = 6). Contextual verbal memory was only administered in Spanish; scores were average (ss = 10). Verbal Fluency administered in English was low (phonemic fluency ss = 5, categorical fluency ss = 6). fMRI verbal tasks were performed in English and revealed left-sided language lateralization.

In pre-surgical epilepsy evaluations of bilingual children, consideration of language is essential. Assessment of language dominance is a minimum requirement in bilingual families, followed by full bilingual evaluation if necessary. In this case, starkly different conclusions regarding lateralization and localization may have been made if the child had not been evaluated in both languages. In English, a significant split between verbal and non-verbal cognition was apparent, possibly suggesting involvement of the dominant left hemisphere. With Spanish testing, this split disappeared, with high average verbal skills. While a growing proportion of children in the US are bilingual, bilingual assessments are not commonly conducted in pre-surgical epilepsy evaluations. In fact, very little work has been done examining language functioning in bilingual epilepsy patients, particularly in children. With both epilepsy-and language-related factors at play in a developing brain, we encourage closer attention to these issues, particularly in the context of neurosurgical procedures.

Many epilepsy syndromes are medically refractory, leading patients to be referred for surgical work-up to control their seizures and improve their quality of life (QOL). Although surgical treatments may reduce or stop seizures, many patients continue to present with declines in mood and/or cognition post-operatively. In addition, pre-operative QOL of patients with medically refractory epilepsy is impacted by executive function (EF). The present study aims to investigate the relationship between post-operative mood/QOL and pre-operative EF in adults with epilepsy. It was hypothesized that mood would remain stable or decline post-operatively; pre-operative EF would be a protective factor for mood decline and QOL.

The sample consisted of 47 adult patients (57.4% female; Age, M= 34.02(11.59)) with medically refractory epilepsy at the UCSF Epilepsy Center. Participants were included if they received surgical treatment for their epilepsy (42.6% right anterior temporal lobectomy [ATL], 46.8% left ATL, 2.1% laser ablation, 6.4% responsive neurostimulation, 2.1% multiple surgical interventions) and received both a pre- and post-surgical neuropsychological evaluation. Most patients were right-handed (95.7% right). Mood and QOL were assessed from pre- and post-operative evaluations using the Beck Depression Inventory- Second Edition (BDI-II), Beck Anxiety Inventory (BAI), and Quality of Life in Epilepsy- 31 (QOLIE-31). Executive function was assessed using the Trail Making Test, and the Delis-Kaplan Executive Function Scale (D-KEFS) subtests Color-Word Interference (CW-I) and Verbal Fluency. Descriptive statistics were obtained for each of the measures listed. A paired sample t-test was conducted between time A and B to determine whether mood and QOL were significantly different. Two multiple regressions were conducted. One analysis for post-operative depression and QOL respectively with pre-operative EF.

At time A, both anxiety and depression were minimal (BDI M= 17.8, SD= 10.34; BAI M= 13; SD= 8.94). QOL was borderline clinically significant (QOLIE M= 37.46, SD= 9.74). Depression at time B was positively correlated with depression at time A (r[45]= 0.316, p=0.035). A paired sample t-test indicated that depression and QOL were significantly different at time A and time B (t[44]= 2.04, p= 0.047; t[31]= -3.34, p= 0.002), with improved scores post-operatively. Anxiety was not significantly different across time points (t[39]= 1.20, p=0.238). Multiple regression analyses indicated that pre-operative depression and EF did not predict post-operative depression (F(5,27)= 1.62, p= 0.189). Pre-operative EF (CW-I Inhibition-Switching), but not pre-operative depression, predicted post-operative QOL (F(4(24)= 3.13, p=.03, R2= .343).

Results were somewhat discrepant from prior research in that depression and QOL improved post-surgically. Notably, while the observed change in depression was statistically significant it was not clinically significant according to literature (Doherty et al., 2021). Pre-surgical inhibitory control predicted QOL, illustrating that EF may serve as a protective factor post-surgically. The present study did not include a measure of seizure freedom classification post-operatively, therefore, future studies should investigate how seizure freedom classification impacts the relationship between mood, QOL, and cognitive outcomes.

Researchers are increasingly finding that the presence of neuronal surface antibodies (NSAb) may account for a larger percentage of outpatient epilepsy cases than previously thought (Elisak et al., 2018; Brenner et al., 2013). However, systematic NSAb screening is not included in standard epilepsy care (Kambadja et al., 2022). The Montreal Cognitive Assessment (MoCA; Nasreddine, 2005) is one of the most commonly used screening tools among physicians (Judge et al., 2019) across various neurological conditions, and has previously been validated in populations with autoimmune encephalitis (Hebert et al., 2018). Because patients with NSAb associated epilepsy often present with cognitive dysfunction (Greco et al., 2006), a MoCA is often administered as part of standard clinical care. The present analysis compared MoCA performance profiles in epilepsy patients with and without the presence of serum NSAbs. We explored what specific cognitive profile, as defined by the MoCA, may predict NSAb positivity.

Forty-eight epilepsy patients were enrolled through an outpatient epilepsy clinic or during non-intensive or elective hospital stays. Participants were eligible if they met one of three diagnostic categories: focal epilepsy of unknown cause (n = 33), lesional focal epilepsy (n = 5), or generalized epilepsy (n = 4). All participants signed consent, underwent a comprehensive interview, which included MoCA testing, and serum NSAb testing paralleling standard clinical practice. Mann-U Whitney tests were run to compare overall MoCA and subgroup domain performance between groups.

Six patients (13%), all with focal epilepsy of unknown cause, had positive NSAb panels (LGI1: n = 3; GAD65: n = 2; CASPR2: n = 1). There was no significant difference in overall MoCA scores between participants with focal epilepsy of unknown cause who were antibody positive versus negative, and antibody positive versus antibody negative lesional or generalized epilepsy. However, when analyzing by MoCA subgroup, we found that antibody positive patients performed significantly worse on delayed recall than antibody negative patients with focal epilepsy of unknown cause (Mdn = 1.5 vs 3), U(Nantibodynegative=27, Nantibodypositive=6) = 69.00, p = .02. There was no significant difference in other MoCA cognitive domain tests, and delayed recall scores did not significantly differ between antibody positive patients and those with lesional focal and generalized epilepsy.

These preliminary findings suggest that episodic memory impairment, as measured by delayed recall on the MoCA, may predict NSAb antibody positivity among patients with focal epilepsy of unknown cause. This may relate to specific predilection of the hippocampal regions in antibody-mediated epileptogenesis and pathology.