Approximately half of all children and adults newly diagnosed with epilepsy also show behavioral and/or cognitive difficulties upon evaluation. While neuropsychological screening is recommended as a routine part of care at seizure onset, in reality, access to care is often restricted by many factors. In order to better define the extent of the problem, we developed a survey to understand how frequently youth with new onset epilepsy currently undergo neuropsychological evaluation or screening and whether virtual assessment tools are used to extend access to care.

We created an online survey to better understand new onset epilepsy care provided within neuropsychological practice settings in the United States and Canada. The survey was disseminated via multiple listservs (e.g., AACN listservs, APPCN, PERF neuropsychologists) and respondents included 45 neuropsychologists. Survey questions were grouped by the following domains: 1) location characteristics (e.g., urban versus rural location, type of practice, affiliation with comprehensive epilepsy center); 2) volume of new onset epilepsy patient cases (e.g., number of neuropsychologists within practice who see new onset patients, percentage of new onset cases who received neuropsychological evaluations/screeners, wait time), and 3) tele-neuropsychology procedures (e.g., use of virtual testing, frequency of virtual testing, frequency of virtual intakes/feedbacks).

Practice locations of the 45 respondents included academic medical center (n=34, 75.6%), community medical center (n=10, 22.2%), and private practice (n=1, 2.2%). All but one respondent practiced in an urban setting. Respondents were generally affiliated with Comprehensive Epilepsy Centers (level 3 or 4) (n=39, 86.7%). Practice settings typically included < 3 epilepsy neuropsychologists (n=29, 65.9%). Of interest, neuropsychological evaluation of new onset pediatric epilepsy patients generally ranged from 0-25% of cases (n=32, 71%; mode=11-25%). Reported barriers included: insurance, poor access to rural populations, interdisciplinary communication, departmental referral patterns, limited number of providers, and need to prioritize pre-surgical patients. In terms of access, neuropsychology waitlist times for patients with nonsurgical epilepsy ranged from <1 to 6 months (n=34, 75%) with an equal proportion of patients waiting 1-3 months (33%) and 4-6 months (33%). Telehealth was not frequently utilized in non-surgical epilepsy test administration (Do not use, n=39; 86.7%), but frequently incorporated for non-testing purposes (i.e., intakes, feedbacks) (n=40, 88.9%).

Results of this provider survey indicate that children with new-onset epilepsy do not routinely undergo neuropsychological evaluation (< 25%). Barriers included prioritizing presurgical workups, referral patterns, access to care, and limited provider bandwidth. Clearly, there is a need to improve access to care. Possible solutions include developing more time efficient screening batteries with measures most sensitive to early cognitive and psychosocial deficits, and incorporating the use of virtual technology all in the service of improving the lives of children with epilepsy.

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 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.

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.

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.

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).

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, and specifically drug-resistant epilepsy (DRE), is associated with an increased risk of psychiatric dysfunction, likely due to a combination of physiological mechanisms, emotional reactions to disease burden, and bi-directional influences. Women with epilepsy warrant special consideration due to many factors, including hormonal influences on seizure susceptibility, reproductive health considerations, and unique psychiatric and clinical profiles. However, there is yet to be large-scale research characterizing women with DRE. The present study characterized psychiatric conditions, treatment, and hospitalization data in a Veterans Health Administration (VHA)-wide sample of women Veterans and then compared results to a male Veteran sample to explore sex differences.

Data from 52,579 Veterans enrolled in VHA care between FY2014 and 2nd Quarter FY2020 were gathered from the VHA Corporate Data Warehouse administrative data. The sample was comprised of 5,983 women (11.4%) and 46,596 men (88.6%). Demographics, psychiatric diagnoses, psychiatric medications, ER visits, and hospitalizations were characterized. Chi-square analyses were used to examine group differences between men and women.

The vast majority of the women Veteran sample had at least one psychiatric diagnosis (86.1%), with over half of the sample diagnosed with depression (68.3%), PTSD (54.1%), and/or anxiety disorders (57.7%). When compared to men, women Veterans were more likely to have a psychiatric diagnosis (86.1% vs. 68.1%), evidenced a higher number of co-morbid psychiatric conditions (2.4 vs. 1.6), and were prescribed more psychiatric medications (3.4 vs. 2.3; all significant at p<0.001). All individual psychiatric diagnoses were more prevalent in women than men and, notably, suicidality was also higher in women (13.5% vs. 10.0%; p < 0.001). Women Veterans also had a higher number of ER visits (6.9 vs. 5.5; p < 0.001) and psychiatric hospitalizations than men (.4 vs. .3, p < 0.001).

The present study represents the largest known investigation to date of women with DRE and is also the largest study of women Veterans with any form of epilepsy. It highlights a vast psychiatric burden in this subset of women Veterans, with high rates of psychiatric comorbidity, lending to downstream effects on psychiatric medication burden and risk for emergency care usage and psychiatric hospitalization. Comparisons to men emphasize that women are differentially impacted by the psychiatric toll of DRE and warrant special consideration. The markedly higher rates of depressive disorders and suicidality in women Veterans with DRE is especially notable when considering risk of harm and mortality. Overall, the present work adds to the paucity of literature of women Veterans with seizures and gaps in the broader DRE research base, with implications for specialized screening and maximizing treatment interventions in this population.

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.

Epilepsy is a chronic neurological disease, and surgery is a common treatment option for persons who do not respond to medication. Neuropsychology plays an important role in the epilepsy presurgical workup, characterizing the cognitive functioning of patients with epilepsy as well as assisting in the determination of which hemisphere seizures originate in the brain through testing of different cognitive functions. NeuroQuant is a relatively newer software that analyzes clinical neuroimaging to quantify brain volume. The objective of this study was to determine if changes in left versus right total hippocampal volume predicted changes in verbal versus nonverbal memory performance.

Cognitive performance and NeuroQuant bilateral hippocampal volume were examined in a cross-sectional sample of 37 patients with epilepsy. All patients had undergone a comprehensive presurgical neuropsychological evaluation as well as magnetic resonance imaging (MRI) and these results were analyzed using a series of linear regression analyses.

Total left hippocampal volume was a significant predictor of delayed verbal free recall (RAVLT F(1, 31) = 4.79, p< .036, RA2 = 0.13, and ß=.37, p<.036). Even when controlling for the effects of biological sex, education, and depression, left hippocampal volume remained a significant predictor (ß=.42, p<.025). Total left hippocampal volume did not predict other verbal memory scores. Total right hippocampal volume was a significant predictor of delayed nonverbal figure recall (RCFT F(1, 31)= 6.46, p<.016), RA2 = .17 and ß=.42) p<.016). When controlling for the effects of biological sex, education, and depression, right hippocampal volume remained a significant predictor (ß=.404, p<.026). Total right hippocampal volume did not predict other nonverbal memory scores.

These findings validate prior research demonstrating the importance of the left hippocampus in verbal memory and right hippocampus in nonverbal memory. Findings also demonstrate the clinical utility of neuropsychological evaluation in determining laterality in the epilepsy presurgical workup process, as well as support NeuroQuants’ inclusion as an additional consideration in that process.

To examine whether suboptimal performance as determined by formal validity testing would predict neurocognitive scores in a sample of 83 pre-surgical, non-litigating epilepsy patients.

Participants were 83 patients who underwent comprehensive outpatient neuropsychological testing as part as their evaluation as epilepsy surgery candidates. The sample consisted of 41 females and 42 males, with 72 patients identifying as White, 5 as Black, 2 as Hispanic, 1 as Asian, and 2 as other. Mean age was 36 (SD=12.4) mean FSIQ was 87 (SD=12.7), mean years of education of 12.9 (SD=2.1). Each patient’s assessment included a stand-alone performance validity test (PVTs)— Word Memory Test (WMT), the Test of Memory Malingering (TOMM), or the Medical Symptom Validity Test (MSVT)—as well as two embedded measures of validity—the California Verbal Learning Test Forced Choice (CVLT FC) and WAIS-IV Reliable Digit Span (RDS). Pass/fail rates were analyzed, with valid performance being defined as pass score on at least two of the completed PVTs (N=73 Pass Effort group 86.9%; N=10 Failed Effort group 11.9%). Point-biserial Pearson correlations were conducted to determine the relationship between validity pass/fail status and WAIS-IV FSIQ, VCI, and PRI scores, CVLT-II Trials 1-5 Total T scores, CVLT-II Long Delay Free Recall z scores, WMS-III Logical Memory II T scores, BVMT Total Recall T scores, BVMT Delayed Recall T scores, and Trail Making Test (TMT) B T scores.

Significant relationships were found between Failed Effort group and all neurocognitive scores except BVMT Total Recall. On average, the Failed Effort group obtained significantly lower FSIQ (M=76.57, SD=10.94), VCI (M=80.89, SD=16.03), PRI (M=81.00, SD=14.91), CVLT-II Trials 1-5 Total (M =34, SD=6.89), CVLT-II Long Delay Free Recall (M =-2.44, SD=1.43), WMS-IV Logical Memory II (M =4.83, SD=2.79), BVMT Delayed Recall (M=26.38, SD=6.41), and TMT B (M=29.70, SD=11.46) standard scores compared to the Pass Effort group (FSIQ M=88.09, SD=12.52; VCI M=92.13, SD=13.61; PRI M=91.14, SD=12.06; CVLT-II Trials 1-5 Total M=47.86, SD=12.02; CVLT- II Long Delay Free Recall M=-.44, SD=1.11; WMS-III Logical Memory II M=8.41, SD=3.17; BVMT Delayed Recall M=39.19, SD=12.66; TMT B M=39.34, SD=13.18). Correlation coefficients were r=-.266* (FSIQ), r=-.255* (VCI), r=-.271* (PRI), r=.361**(CVLT-II Total), r=-.474** (CVLT-II LDFR), r=-.298** (WMS-IV LM II), r=-.308** (BVMT DR), and r=-.240* (TMTB). All coefficients were significant at the .05 (*) or .01 (**) level.

Results suggest that pass/fail status on formal validity testing predicts depressed performance on a variety of neurocognitive measures. Therefore, predicting surgical outcome of resection/ablation (e.g., compensation of contralateral hemisphere) should not be based upon neuropsychological memory performance alone when there are failures on tests of engagement as memory scores have strong correlations to pass/fail status on formal validity testing. Overall, this emphasizes the importance of routinely integrating PVTs as part of pre-epilepsy surgery neuropsychological evaluations.

Previous studies have demonstrated a high prevalence of social and emotional problems in young adults with a history of childhood epilepsy, with social skill impairment hypothesized to play a significant role in these outcomes. Few studies have examined social skills within children with epilepsy and very few have examined this within the context of other neuropsychological and neurological variables. This study aims to examine the association between social problems and other relevant neuropsychological variables (IQ, adaptive functioning, social skills) within the pediatric epilepsy population.

Participants were 86 epilepsy patients between the ages 5 and 18 years of age who were referred for neuropsychological assessment as a part of their surgical candidacy work-up. Pearson correlation analysis was conducted to examine the correlations between performance on objective measures of full-scale IQ, and parent ratings on questionnaires assessing parent perception of the patients’ overall adaptive functioning, social skills, and social problems.

As expected, earlier age of onset was associated with lower IQ, which itself was associated with weaker overall daily living skills and social skills. Later age of seizure onset was associated greater social problems. Social skills were not correlated with social problems.

The results of this study suggest that children with later age of onset of seizures, are at increased risk of social problems and that these problems may not related to social skill impairment. Implications for clinical practice and future directions are discussed.

Memory impairment is a common comorbidity in individuals with temporal lobe epilepsy (TLE). Further, in medication-resistant epilepsy the frontline option, neurosurgical epileptogenic zone destruction, places memory at significant risk. Research has highlighted that TLE causes whole-brain network efficiency disruption, but it is not established how this may explain pre- and post-surgical cognition. Here we examine whether white matter structural network organization predicts pre-operative memory function and/or risk for post-operative memory decline.

Patients with drug-resistant TLE were recruited from two epilepsy centers in a prospective longitudinal study. The pre-operative sample included 51 individuals with left TLE (L-TLE), 52 with right TLE (R-TLE), and 57 healthy controls who underwent T1- and diffusion-weighted MRI (dMRI), and neuropsychological tests of verbal and visual memory. Forty-four patients (n=21 L-TLE) subsequently underwent temporal lobe surgery (36 anterior temporal lobectomy; 7 stereotactic laser amygdalohippocampectomy; 1 amygdalohippocampectomy) and completed post-operative memory testing. Whole-brain connectomes were generated via diffusion tractography and analyzed using graph theory, focusing on network integration (path length) and specialization (transitivity). In the preoperative dataset, first we compared TLE versus controls with analysis of covariance (ANCOVAs) controlling for age. Next, linear regressions examined the association between memory scores and network efficiency between L-TLE, R-TLE and controls. In the post-operative sample, bivariate correlations examined the association between pre- to post-operative memory change and 1) global network efficiency and 2) asymmetry of mesial temporal efficiency (i.e., local efficiency of the hippocampal, parahippocampal, and entorhinal nodes). Finally, efficiency metrics were entered into stepwise regressions along with established predictors of memory decline.

Compared to controls, TLE showed longer path length (p < .05; ηp2 = .03) and lower transitivity (p = .01; ηp2 = .04). Pre-operatively, better verbal learning and memory were associated with both shorter path length (β = -0.23 to -0.32; psadjusted < .05) and increased transitivity (β = 0.20 to 0.31; psadjusted < .05). These associations were greater in L-TLE than R-TLE (i.e., a significant interaction; β = -0.29 to 0.25; psadjusted <.05). Post-operatively, global metrics predicted decline on list learning for LTLEs (rs = -.57 to .58; ps < .01), and were marginal on list recall (rs = -.42 to .40; ps < .10). Leftward asymmetry of mesial temporal local efficiency predicted greater decline across most verbal memory measures for L-TLE (rs -.47 to -59; psadjusted <.05), but not R-TLE. Asymmetry of mesial network efficiency uniquely explained at least 20 to 43% of the variance in list learning, recall, and story learning for L-TLE, outperforming hippocampal asymmetry and preoperative score (psadjusted <.05).

Our findings suggest that global white matter network abnormalities contribute to verbal memory impairment pre-operatively and vulnerability to decline post-operatively in L-TLE. Asymmetry of a predefined mesial temporal sub-network may help predict post-operative memory function following left temporal lobe surgery, such that greater efficiency in the to-beresected mesial temporal network may be an important risk factor for decline. Our findings extend the importance of network approaches in TLE to include the relationships between neurobiological networks and memory function.

Cannabis is classified as a class B drug in the UK with penalties for possession of up to 5 years in prison, an unlimited fine or both. Nevertheless it is widely available and is the most commonly used drug in the UK with approximately 2.6 million (7.6%) of adults reporting that they sometimes or regularly use it. It is not uncommon for people who present in our epilepsy clinic to report regular use of cannabis; some use it recreationally whilst others report ‘self-medicating’ based on the belief that it has a beneficial impact on their seizures. The aim of this study was to establish the prevalence of cannabis use in people with epilepsy referred for a neuropsychological assessment and to examine the impact of cannabis use on cognitive function in this group.

All patients who attend for a neuropsychological assessment are routinely asked about illegal drug use in their clinical interview. This information is also captured in the medical and neuropsychiatric assessments they undergo when assessed by the multidisciplinary team. The electronic medical records of 800 consecutive patients who had undergone a neuropsychological assessment between 2019 and 2022 were searched for references to cannabis use. The neuropsychological profiles of patients reporting cannabis use were compared to those seen in the larger series across multiple cognitive domains.

Seventy (8.75%) of the patients in the series reported past or present cannabis use. Cannabis users were more likely to be male (p<0.01) and were younger (p<0.01) than those who did not report use. Reading IQ was significantly lower in the cannabis group (p<0.001). Patients who were regularly using cannabis at the time of the neuropsychological assessment did not differ from the rest of the cohort on tests of processing speed, working memory, naming or verbal fluency. There were no differences between the groups in their performance on an embedded measure of performance validity. However the patients who were regularly using cannabis at the time of their neuropsychological assessments scored significantly lower on tests of verbal learning (p<0.05) and reported significantly greater subjective memory problems in everyday life (p=0.02) than the non-cannabis group. The group using cannabis also scored significantly more highly on the depression (p<0.01) and anxiety scales (p=0.02) on the Hospital Anxiety and Depression Scale.

The prevalence and patterns of cannabis use in the epilepsy population mirror those seen in the wider population. The impact on regular cannabis use on neuropsychological function appears to be most evident on measures of new learning and subjective measures of memory disturbance. Cannabis use is significantly associated with lower levels of cognitive reserve and elevated levels of anxiety and low mood. Whilst caution must be employed with respect to any direct attribution in these complex clinical presentations, these findings may be helpful in the interpretation of neuropsychological test scores and the planning of interventions, particularly with respect to subjective memory complaints in this group.

To apply the new IC-CoDE cognitive diagnostic taxonomy (Norman et al., 2020) to a large cohort of people with temporal lobe epilepsy (TLE) in India. The IC-CoDE taxonomy of cognitive diagnoses for 1,409 Englishspeaking adults with TLE from seven epilepsy centres in the U.S. has been published (McDonald et al., 2022). Initial results suggest that the IC-CoDE produces stable cognitive phenotypes across centres; however, its international applicability, including the suggested impairment cut-off needs to be considered across cultures and languages to avoid misclassification. The aim of this study was to apply the IC-CoDE to a population, outside of the U.S., diverse in language representation (i.e., bi/multi-lingual), assessment tools, normative data, and educational and cultural backgrounds to determine whether the same cognitive phenotypes and their relative frequencies would emerge.

Data from 549 adults with TLE (mean age=27.14 (8.04), 60.47% males) from a tertiary referral hospital in Mumbai, India who had undergone a comprehensive neuropsychological evaluation (minimum two tests in at least 4 of the 5 cognitive domains: memory, language, executive function, attention/processing speed and visuospatial) were analysed using the ICCoDE criteria. The base rate of impairment for individual tests was calculated using a cutoff of 1.5 standard deviations (S.D.) below the normative mean. The cognitive diagnostic criteria were applied, and the distribution and base rate of cognitive phenotypes was compared to the published taxonomy data from the U.S. (McDonald et al., 2022).

In comparison to the U.S. cohort, the India group was relatively younger, lower in the education level, had a younger age at seizure onset and a shorter duration of the epilepsy. Application of the IC-CoDE taxonomy using a 1.5 S.D. cutoff revealed an Intact cognitive profile in 48% of patients, Single Domain impairment in 32%, Bi Domain impairment in 15% and Generalised impairment in 5%. These findings were mostly comparable to percentages reported in the U.S. cohorts with Intact profile (47%; c2= 0.158, p=0.690), Single Domain (29%; c2= 46.26, p<0.01), Bi Domain (16%; c2= 0.298, p=0.585) and Generalised (8%; c2= 5.347, p=0.021) impairment. However, the most common impairment in the Single Domain group for the bi/multilingual India population was Memory (38%) followed by Attention (20%) and then Language (13%), diverging from the distribution in the U.S. data with maximum impairment in Language (49%) followed by Memory (32%) in the Single Domain Group.

These findings demonstrate that the IC-CoDE can be applied internationally, and the broad taxonomy of cognitive diagnosis holds even in a culturally, linguistically diverse population. Differences in rates of impairments across specific domains emerged with language relatively preserved in the India bi/multilingual population, and memory more frequently impaired than observed in the multi-centre U.S. sample. These findings may reflect differences in demographics, rates of bi/multilingualism, normative data, language tools, or underlying neuropathology, which should be further explored to determine their impact on cognitive profiles.

A rich literature exists on cognitive changes related to focal injury in the adult brain. In contrast, the developing brains of children are less understood. In contrast to adult cases, 20% to 25% of perinatal strokes result in language disorder regardless of lesion lateralization. Existing literature suggests children with perinatal stroke may present with a range of executive functioning and visuospatial processing difficulties. Gross and fine motor challenges are also likely to occur. Furthermore, these children have an increased prevalence of autism spectrum disorder (ASD) and carry the highest risk for epilepsy. Despite growing research on neurodevelopmental profiles in patients with perinatal stroke, published literature is limited.

Our study examines neurodevelopment of a 2-year-old, right-handed male with a history of perinatal ischemic right middle cerebral artery (MCA) stroke, infantile spasms, and left hemiparesis following right hemispherectomy for seizure management who underwent two neurodevelopmental evaluations at our medical center over approximately 3 years.

Findings from the patient’s evaluation with the Mullen Scales of Early Learning revealed overall cognitive ability in the low average range (SS = 89, 23rd percentile); however, notable variability was seen in his performance. His receptive language was average (SS = 98, 45th %tile) and consistent with previous evaluation results, and he has made gains in visual reception (from SS = 75, 5th %tile to SS = 91, 27th %tile) and expressive language (from SS = 55, 0.1st %tile to SS = 70, 2nd %tile). In addition, his gross motor was exceptionally low (SS = 55, 0.1st %tile) and consistent with previous evaluation results. Fine motor was low average (SS = 84, 14th %tile).

Our patient showed cognitive gains in language and visual reception since his prior evaluation despite history of right MCA stroke and right hemispherectomy. Improvements are likely due to a combination of early brain plasticity and intensive therapies he has received. Consistent with published findings in this population, he experienced seizures associated with his stroke. Our results add to the limited literature on neurodevelopmental challenges associated with perinatal stroke and progress that can be made when appropriate supports are provided early and consistently.

Epilepsy includes recurrent, unprovoked seizures and affects 470,000 children in the US, of which 7% have drug-resistant epilepsy due to failing two or more antiseizure medication trials. For some patients with drug-resistant epilepsy, surgery has been successful in reducing seizure burden. Functional MRI (fMRI) and intracranial mapping of neurocognitive functions, especially language, are increasingly done to assess potential functional loss from epilepsy surgery. However, these procedures vary by medical institute. The purpose of this review was to examine published literature on fMRI and intracranial mapping procedures for pediatric epilepsy surgery workup toward development of a standardized protocol that can be used across institutes as a guide to standard-of-care best practices for predicting loss of function associated with epilepsy surgery.

Our literature review includes information from 8 electronic databases for peer-reviewed, English language studies of evaluation for pediatric epilepsy surgery candidacy. Thirty-one studies were selected based on inclusion criteria. Only studies including fMRI and intracranial mapping conducted with pediatric patients being worked up for epilepsy surgery were selected.

Our review revealed that the most common task used in fMRI and intracranial mapping procedures is visual-object naming, but type of naming tasks and the way they are administered varies widely across medical institutes and includes published measures and those created on site. Variability makes examining findings across studies and designing best practice for these procedures challenging.

Creating gold-standard procedures for fMRI and intracranial mapping administration for epilepsy surgery evaluations is critical in optimizing treatment and functional outcomes for our pediatric patients. Our review is an initial step in this process.

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.

The International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) is a new consensus-based taxonomy that classifies patients into one of four cognitive phenotypes (i.e., cognitively intact, single-domain impairment, bi-domain impairment, generalized impairment). The IC-CoDE has been effectively applied to patients with temporal lobe epilepsy (TLE), but little is known about the relationship between pre-operative cognitive phenotype and post-operative cognitive outcome following epilepsy surgery. The purpose of this study was to examine whether the IC-CoDE classifications are related to memory decline following surgery for TLE.

347 patients (ages 16-66; 57% female) with pharmacoresistant TLE completed comprehensive pre- and post-surgical neuropsychological assessments. Patients were classified into IC-CoDE phenotypes based on pre-surgical pattern of cognitive impairment using a threshold of >1.5 standard deviations (SD) below the normative mean. Change scores were calculated from delay trial scores of the following memory tests: Rey Auditory Verbal Learning Test (RAVLT), and Logical Memory (LM) and Verbal Paired Associates (VPA) subtests from the Wechsler Memory Scale - Third Edition (WMS-III). Cutoffs were applied using epilepsy-specific reliable change indices and patients were classified within the ‘decline’ group if they experienced significant decline on any of the three memory measures.

The distribution of IC-CoDE phenotypes in our sample were as follows: 57% intact, 29% single-domain, 10% bi-domain, and 5% generalized impairment. 108 patients (31%) demonstrated post-surgical memory decline. Patients who underwent dominant temporal lobectomy were more likely to show post-surgical memory decline compared to non-dominant temporal lobectomy. However, there was no significant difference in phenotype distribution between patients who underwent left versus right-sided resections; thus, analyses were conducted on the entire sample to increase power. Chi-square analyses revealed unique patterns of post-surgical memory decline across phenotypes, X2 = 8.79, p = .032. There was a significantly higher proportion of patients with memory decline in the single-domain phenotype (39%) and this was followed by the bi-domain phenotype (33%) and the intact phenotype (29%). In contrast, patients with generalized impairment were unlikely to show memory decline (.06%). Within the single domain impaired phenotype, there were no differences between the specific domains impaired and memory decline. Logistic regression model was also significant; after controlling for surgery side, the IC-CoDE phenotypes significantly predicted the likelihood of a patient experiencing post-surgical memory decline; X2 = 8.18, p = .043.

In addition to the IC-CoDE providing a useful cognitive classification scheme in epilepsy, the IC-CoDE phenotypes appear helpful in identifying those at risk for post-operative memory decline. Previous literature has suggested that those with better pre-surgical cognition are generally at highest risk for cognitive decline. Our results generally follow this trend, but interestingly, patients with single domain impairment were at the highest risk of memory decline, even above those in the cognitively intact group. Future studies are important to confirm this pattern in other samples and examine additional contributing factors and underlying mechanisms that may influence risk of memory decline across these cognitive phenotypes.

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.

Pediatric patients with frontal lobe epilepsy (FLE) have higher rates of attention deficit hyperactivity disorder (ADHD), as well as executive functioning (EF) and fine motor (FM) challenges. Relations between these constructs have been established in youth with ADHD and are supported by FM and EF skill involvement in frontal-subcortical systems. Still, they are not well understood in pediatric FLE. We hypothesized that poorer FM performance would be related to greater executive dysfunction and ADHD symptomatology in this group.

47 children and adolescents with FLE (AgeM=12.47, SD=5.18; IQM=84.07; SD=17.56; Age of Seizure OnsetM=6.85, SD=4.64; right-handed: n=34; left-handed: n=10; Unclear: n=3) were enrolled in the Pediatric Epilepsy Research Consortium dataset as part of their phase I epilepsy surgical evaluation. Participants were selected if they had unifocal FLE and completed the Lafayette Grooved Pegboard (GP). Seizure lateralization (left-sided: n=19; right-sided: n=26; bilateral: n=2) and localization were established via data (e.g., EEG, MRI) presented at a multidisciplinary team case conference. Patients completed neuropsychological measures of FM, attention, and EF. Parents also completed questionnaires inquiring about their child’s everyday EF and ADHD symptomatology. Correlational analyses were conducted to examine FM, EF, and ADHD relations.

Dominant hand (DH) manual dexterity (GP) was related to parent-reported EF (Behavior Rating Inventory of Executive Function, Second Edition [BRIEF-2]-Global Executive Composite [GEC]: r(15) =-.70, p<.01, d=1.96). While not statistically significant, medium to large effect sizes were found for GP DH and parent-reported inattention (Behavior Assessment System for Children, Third Edition [BASC-3]-Attention Problems: r(12)=-.39, p=.17, d=.85) and hyperactivity/impulsivity (BASC-3-Hyperactivity: r(11)= -.44, p=.13, d=.98), as well as performance-based attention (Conners Continuous Performance Test, Third Edition -Omission Errors: r(12)=-.35, p=.22, d=.41), working memory (Wechsler Intelligence Scale for Children - Fifth Edition [WISC-V]-Digit Span [DS]: r(19)=.38, p=.09, d=.82) and cognitive flexibility (Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Category Switching: r(13)=.46, p=.08, d=1.04); this suggests that these relations may exist but that our study was underpowered to detect them. Non-dominant hand (NDH) manual dexterity was related to performance-based working memory (WISC-V-DS: r(19)=.50, p<.01, d=1.12) and cognitive flexibility (D-KEFS-Trails Making Test Number-Letter Switching: r(17)=.64, p<.01, d=1.67). Again, while underpowered, medium to large effect sizes were found for GP NDH and parent-reported EF (BRIEF-2 GEC: r(15) =-.45, p=.07, d=1.01) and performance-based phonemic fluency (D-KEFS-Letter Fluency: r(13)=.31, p=.20, d=.65).

Our findings suggest that FM, EF, and ADHD are related in youth with FLE; however, these relations appear to vary by skill and hand. We posit that our findings are due in part to the frontal-cerebellar networks given their anatomic proximity between frontal motor areas and the dorsolateral prefrontal cortex - as well as their shared functional involvement in these networks. Future studies should evaluate the predictive validity of initial FM skills for later executive dysfunction and ADHD symptomatology in FLE. If such relations emerge, contributions of early FM interventions on EF development should be examined. Further replication of these findings with a larger sample is warranted.