A user's guide for the International Classification of Cognitive Disorders in Epilepsy.

To present the background, rationale, details pertaining to use and essential computational steps, synopsis of findings to date, and future directions for the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE)-an initiative of the ILAE Neuropsychology Task Force. Examined are: (a) the 6 steps leading to the derivation of a cognitive phenotype from neuropsychological test data with an accompanying case example, (b) concise review of all IC-CoDE research to date, (c) summary of identified correlates of IC-CoDE outcomes, and (d) future research and clinical directions for the initiative. The IC-CoDE is computationally uncomplicated with individual or group data and represents a novel approach leading to new insights in the neuropsychology of epilepsy, with applications to diverse datasets internationally informing the reliability and validity of the approach. The IC-CoDE represents a novel approach to the analysis and interpretation of neuropsychological data in epilepsy that offers to advance a global taxonomy of cognitive disorders in epilepsy facilitating international collaboration and big data science.

Individual- and community-level social determinants of health are associated with cognition in older adults with focal epilepsy.

OBJECTIVE: Epilepsy is associated with significant health disparities, including access to specialized care and adverse outcomes that have been associated with several social determinants of health (SDOH). We sought to examine the relationship between individual- and community-level SDOH and cognitive outcomes in older adults with epilepsy. MATERIALS AND METHODS: We collected clinical, SDOH, and neuropsychological data in 57 older adults with epilepsy. Individual-level SDOH included patient factors (quality of education, income, insurance, marital status) and early-life environmental factors (parental education and occupation, childhood employment). Neighborhood deprivation was measured with the Area Deprivation Index (ADI). Stepwise regressions were conducted to examine the independent contribution of individual-level SDOH to cognitive performance, and Spearman rho correlations were conducted to examine the relationship between ADI and cognitive performance. The SDOH profiles of patients who met the criteria for cognitive impairment were examined. RESULTS: After controlling for clinical variables, patient factors (public health insurance, poorer quality of education) and early-life environmental factors (lower mother's education, lower father's and mother's occupational complexity, history of childhood employment) were significant predictors of lower performance on measures of global cognition, verbal learning and memory, processing speed, and executive function. Higher ADI values (greater disadvantage) were associated with lower scores on global cognitive measures, verbal learning and memory, and executive function. Patients who met criteria for cognitive impairment had, on average, a greater number of adverse SDOH, including lower household incomes and father's education, and higher ADI values compared to those who were cognitively intact. CONCLUSION: We provide new evidence of the role of individual- and community-level SDOH on cognitive outcomes in older adults with epilepsy. This emerging literature highlights the need to examine SDOH beyond epilepsy-related clinical factors. These data could inform the development of interventions focused on increasing access to epilepsy care, education, and resources and promoting brain and cognitive health within the most at-risk communities.

Cross-cultural application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE): Cognitive phenotypes in people with temporal lobe epilepsy in India.

OBJECTIVE: Efforts to understand the global variability in cognitive profiles in patients with epilepsy have been stymied by the lack of a standardized diagnostic system. This study examined the cross-cultural applicability of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) in a cohort of patients with temporal lobe epilepsy (TLE) in India that was diverse in language, education, and cultural background. METHODS: A cohort of 548 adults with TLE from Mumbai completed a presurgical comprehensive neuropsychological evaluation. The IC-CoDE taxonomy was applied to derive cognitive phenotypes in the sample. Analyses of variance were conducted to examine differences in demographic and clinical characteristics across the phenotypes, and chi-squared tests were used to determine whether the phenotype distribution differed between the Mumbai sample and published data from a multicenter US sample. RESULTS: Using the IC-CoDE criteria, 47% of our cohort showed an intact cognitive profile, 31% a single-domain impairment, 16% a bidomain impairment, and 6% a generalized impairment profile. The distribution of cognitive phenotypes was similar between the Indian and US cohorts for the intact and bidomain phenotypes, but differed for the single and generalized domains. There was a larger proportion of patients with single-domain impairment in the Indian cohort and a larger proportion with generalized impairment in the US cohort. Among patients with single-domain impairment, a greater proportion exhibited memory impairment in the Indian cohort, whereas a greater proportion showed language impairment in the US sample, likely reflecting differences in language administration procedures and sample characteristics including a higher rate of mesial temporal sclerosis in the Indian sample. SIGNIFICANCE: Our results demonstrate the applicability of IC-CoDE in a group of culturally and linguistically diverse patients from India. This approach enhances our understanding of cognitive variability across cultures and enables harmonized and inclusive research into the neuropsychological aspects of epilepsy.

Validity of the MoCA as a cognitive screening tool in epilepsy: Are there implications for global care and research?

OBJECTIVE: This study evaluated the diagnostic performance of a widely available cognitive screener, the Montreal cognitive assessment (MoCA), to detect cognitive impairment in older patients (age ≥ 55) with epilepsy residing in the US, using the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) as the gold standard. METHODS: Fifty older adults with focal epilepsy completed the MoCA and neuropsychological measures of memory, language, executive function, and processing speed/attention. The IC-CoDE taxonomy divided participants into IC-CoDE Impaired and Intact groups. Sensitivity and specificity across several MoCA cutoffs were examined. Spearman correlations examined relationships between the MoCA total score and clinical and demographic variables and MoCA domain scores and individual neuropsychological tests. RESULTS: IC-CoDE impaired patients demonstrated significantly lower scores on the MoCA total, visuospatial/executive, naming, language, delayed recall, and orientation domain scores (Cohen's d range: 0.336-2.77). The recommended MoCA cutoff score < 26 had an overall accuracy of 72%, 88.2% sensitivity, and 63.6% specificity. A MoCA cutoff score < 24 yielded optimal sensitivity (70.6%) and specificity (78.8%), with overall accuracy of 76%. Higher MoCA total scores were associated with greater years of education (p = 0.016) and fewer antiseizure medications (p = 0.049). The MoCA memory domain was associated with several standardized measures of memory, MoCA language domain with category fluency, and MoCA abstraction domain with letter fluency. SIGNIFICANCE: This study provides initial validation of the MoCA as a useful screening tool for older adults with epilepsy that can be used to identify patients who may benefit from comprehensive neuropsychological testing. Further, we demonstrate that a lower cutoff (i.e., <24) better captures cognitive impairment in older adults with epilepsy than the generally recommended cutoff and provides evidence for construct overlap between MoCA domains and standard neuropsychological tests. Critically, similar efforts in other regions of the world are needed. PLAIN LANGUAGE SUMMARY: The Montreal cognitive assessment (MoCA) can be a helpful tool to screen for cognitive impairment in older adults with epilepsy. We recommend that adults 55 or older with epilepsy who score less than 24 on the MoCA are referred to a neuropsychologist for a comprehensive evaluation to assess any changes in cognitive abilities and mood.

Arterial spin labeled perfusion MRI for the assessment of radiation-treated meningiomas.

Purpose: Conventional contrast-enhanced MRI is currently the primary imaging technique used to evaluate radiation treatment response in meningiomas. However, newer perfusion-weighted MRI techniques, such as 3D pseudocontinuous arterial spin labeling (3D pCASL) MRI, capture physiologic information beyond the structural information provided by conventional MRI and may provide additional complementary treatment response information. The purpose of this study is to assess 3D pCASL for the evaluation of radiation-treated meningiomas. Methods: Twenty patients with meningioma treated with surgical resection followed by radiation, or by radiation alone, were included in this retrospective single-institution study. Patients were evaluated with 3D pCASL and conventional contrast-enhanced MRI before and after radiation (median follow up 6.5 months). Maximum pre- and post-radiation ASL normalized cerebral blood flow (ASL-nCBF) was measured within each meningioma and radiation-treated meningioma (or residual resected and radiated meningioma), and the contrast-enhancing area was measured for each meningioma. Wilcoxon signed-rank tests were used to compare pre- and post-radiation ASL-nCBF and pre- and post-radiation area. Results: All treated meningiomas demonstrated decreased ASL-nCBF following radiation (p < 0.001). Meningioma contrast-enhancing area also decreased after radiation (p = 0.008) but only for approximately half of the meningiomas (9), while half (10) remained stable. A larger effect size (Wilcoxon signed-rank effect size) was seen for ASL-nCBF measurements (r = 0.877) compared to contrast-enhanced area measurements (r = 0.597). Conclusions: ASL perfusion may provide complementary treatment response information in radiation-treated meningiomas. This complementary information could aid clinical decision-making and provide an additional endpoint for clinical trials.

Impact of white matter networks on risk for memory decline following resection versus ablation in temporal lobe epilepsy.

BACKGROUND: With expanding neurosurgical options in epilepsy, it is important to characterise each options' risk for postoperative cognitive decline. Here, we characterise how patients' preoperative white matter (WM) networks relates to postoperative memory changes following different epilepsy surgeries. METHODS: Eighty-nine patients with temporal lobe epilepsy with T1-weighted and diffusion-weighted imaging as well as preoperative and postoperative verbal memory scores (prose recall) underwent either anterior temporal lobectomy (ATL: n=38) or stereotactic laser amygdalohippocampotomy (SLAH; n=51). We computed laterality indices (ie, asymmetry) for volume of the hippocampus and fractional anisotropy (FA) of two deep WM tracts (uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF)). RESULTS: Preoperatively, left-lateralised FA of the ILF was associated with higher prose recall (p<0.01). This pattern was not observed for the UF or hippocampus (ps>0.05). Postoperatively, right-lateralised FA of the UF was associated with less decline following left ATL (p<0.05) but not left SLAH (p>0.05), while right-lateralised hippocampal asymmetry was associated with less decline following both left ATL and SLAH (ps<0.05). After accounting for preoperative memory score, age of onset and hippocampal asymmetry, the association between UF and memory decline in left ATL remained significant (p<0.01). CONCLUSIONS: Asymmetry of the hippocampus is an important predictor of risk for memory decline following both surgeries. However, asymmetry of UF integrity, which is only severed during ATL, is an important predictor of memory decline after ATL only. As surgical procedures and pre-surgical mapping evolve, understanding the role of frontal-temporal WM in memory networks could help to guide more targeted surgical approaches to mitigate cognitive decline.