Cognitive decline and quality of life after resective epilepsy surgery.

OBJECTIVES: The objectives of this study were to examine the association between cognitive decline and quality of life (QoL) change in a large sample of individuals with drug-resistant epilepsy who underwent resective surgery and to examine whether the association between cognitive decline and QoL is differentially affected by seizure classification outcome (Engel Class 1 vs. 2-4) or side of surgery (left vs. right hemisphere). MATERIALS AND METHODS: The sample comprised 224 adults (ages ≥ 18) with drug-resistant focal epilepsy treated with resective surgery who underwent comprehensive pre-operative and post-operative evaluations including neuropsychological testing and the Quality of Life in Epilepsy Inventory - 31 between 1991 and 2020. Linear mixed-effects models were fit to examine subject-specific trajectories and assess the effects of time (pre- to post-operative), cognitive decline (number of measures that meaningfully declined), and the interaction between time and cognitive decline on pre- to post-operative change in QoL. RESULTS: Increases in QoL following resection were observed (B = -10.72 [SE = 1.22], p < .001; mean difference between time point 1 and time point 2 QoL rating = 8.11). There was also a main effect of cognitive decline on QoL (B = -.85 [SE = .27], p = .002). Follow-up analyses showed that the number of cognitive measures that declined was significantly associated with post-surgical QoL, (r = -.20 p = .003), but not pre-surgical QoL, (r = -.04 p = .594), and with pre-to post-surgery raw change in QoL score, (r = -.18 p = .009). A cognitive decline by time point interaction was observed, such that those who had greater cognitive decline had less improvement in overall QoL following resection (B = .72 [SE = .27], p = .009). Similar results were observed within the Engel Class 1 outcome subgroup. However, within the Engel Class 2-4 outcome subgroup, QoL improved following resection, but there was no main effect of cognitive decline or interaction between cognitive decline and time point on QoL change. There was no main effect of resection hemisphere on overall QoL, nor were there interactions with hemisphere by time, hemisphere by cognitive decline, or hemisphere by time by cognitive decline. CONCLUSIONS: Quality of life improves following epilepsy surgery. Participants who had cognitive decline across a greater number of measures experienced less improvement in QoL post-operatively overall, but there was no clear pattern of domain-specific cognitive decline associated with change in QoL. Our results indicate that cognitive decline in a diffuse set of cognitive domains negatively influences post-operative QoL, particularly for those who experience good seizure outcomes (i.e., seizure freedom), regardless of the site or side of resection.

Reliable change on the selective reminding test in a series of left-hemisphere language dominant patients with right temporal lobe epilepsy.

The Selective Reminding Test (SRT) is widely used in pre-surgical evaluations for people with epilepsy; however, important characteristics such as reliability and stability over time within an epilepsy-specific control cohort are unclear. In this study, we document test-retest reliabilities, practice effects, and Reliable Change Indices (RCI) for this test in a sample of right temporal lobe epilepsy patients who are left hemisphere dominant for language and underwent surgical resection on the right temporal lobe. A sample of 101 adults with a right temporal lobe seizure focus (mean age = 38.5) was administered the SRT pre- and post-right temporal lobe surgery. Test-retest reliabilities were modest (r = 0.44-0.59). Practice effects were minimal (0.25-2.04). Reliable Change Indices were calculated and ranged from 4 to 26 depending on the SRT index. The RCI's indicate that relatively moderate to large changes on the SRT are needed for a change score to be considered a significant change in an individual's performance. The RCIs can be used to detect a reliable change in patients undergoing left temporal lobe epilepsy surgery who are at significant risk for verbal memory decline.

Application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) to frontal lobe epilepsy using multicenter data.

RATIONALE: The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) was recently introduced as a consensus-based, empirically-driven taxonomy of cognitive disorders in epilepsy and has been effectively applied to patients with temporal lobe epilepsy (TLE). The purpose of this study was to apply the IC-CoDE to patients with frontal lobe epilepsy (FLE) using national multicenter data. METHODS: Neuropsychological data of 455 patients with FLE aged 16 years or older were available across four US-based sites. First, we examined test-specific impairment rates across sites using two impairment thresholds (1.0 and 1.5 standard deviations below the normative mean). Following the proposed IC-CoDE guidelines, patterns of domain impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) to construct phenotypes. Impairment rates and distributions across phenotypes were then compared with those found in patients with TLE for which the IC-CoDE classification was initially validated. RESULTS: The highest rates of impairment were found among tests of naming, verbal fluency, speeded sequencing and set-shifting, and complex figure copy. The following IC-CoDE phenotype distributions were observed using the two different threshold cutoffs: 23-40% cognitively intact, 24-29% single domain impairment, 13-20% bi-domain impairment, and 18-33% generalized impairment. Language was the most common single domain impairment (68% for both thresholds) followed by attention and processing speed (15-18%). Overall, patients with FLE reported higher rates of cognitive impairment compared with patients with TLE. CONCLUSIONS: These results demonstrate the applicability of the IC-CoDE to epilepsy syndromes outside of TLE. Findings indicated generally stable and reproducible phenotypes across multiple epilepsy centers in the U.S. with diverse sample characteristics and varied neuropsychological test batteries. Findings also highlight opportunities for further refinement of the IC-CoDE guidelines as the application expands.

Hippocampal Volumes in Amnestic and Non-Amnestic Mild Cognitive Impairment Types Using Two Common Methods of MCI Classification.

OBJECTIVES: Mild cognitive impairment (MCI) types may have distinct neuropathological substrates with hippocampal atrophy particularly common in amnestic MCI (aMCI). However, depending on the MCI classification criteria applied to the sample (e.g., number of abnormal test scores considered or thresholds for impairment), volumetric findings between MCI types may change. Additionally, despite increased clinical use, no prior research has examined volumetric differences in MCI types using the automated volumetric software, Neuroreader™. METHODS: The present study separately applied the Petersen/Winblad and Jak/Bondi MCI criteria to a clinical sample of older adults (N = 82) who underwent neuropsychological testing and brain MRI. Volumetric data were analyzed using Neuroreader™ and hippocampal volumes were compared between aMCI and non-amnestic MCI (naMCI). RESULTS: T-tests revealed that regardless of MCI classification criteria, hippocampal volume z-scores were significantly lower in aMCI compared to naMCI (p's < .05), and hippocampal volume z-scores significantly differed from 0 (Neuroreader™ normative mean) in the aMCI group only (p's < .05). Additionally, significant, positive correlations were found between measures of delayed recall and hippocampal z-scores in aMCI using either MCI classification criteria (p's < .05). CONCLUSIONS: We provide evidence of correlated neuroanatomical changes associated with memory performance for two commonly used neuropsychological MCI classification criteria. Future research should investigate the clinical utility of hippocampal volumes analyzed via Neuroreader™ in MCI.

Memory Performance and Quantitative Neuroimaging Software in Mild Cognitive Impairment: A Concurrent Validity Study.

OBJECTIVE: This study examined the relationship between patient performance on multiple memory measures and regional brain volumes using an FDA-cleared quantitative volumetric analysis program - Neuroreader™. METHOD: Ninety-two patients diagnosed with mild cognitive impairment (MCI) by a clinical neuropsychologist completed cognitive evaluations and underwent MR Neuroreader™ within 1 year of testing. Select brain regions were correlated with three widely used memory tests. Regression analyses were conducted to determine if using more than one memory measures would better predict hippocampal z-scores and to explore the added value of recognition memory to prediction models. RESULTS: Memory performances were most strongly correlated with hippocampal volumes than other brain regions. After controlling for encoding/Immediate Recall standard scores, statistically significant correlations emerged between Delayed Recall and hippocampal volumes (rs ranging from .348 to .490). Regression analysis revealed that evaluating memory performance across multiple memory measures is a better predictor of hippocampal volume than individual memory performances. Recognition memory did not add further predictive utility to regression analyses. CONCLUSIONS: This study provides support for use of MR Neuroreader™ hippocampal volumes as a clinically informative biomarker associated with memory performance, which is a critical diagnostic feature of MCI phenotype.

Survey of evaluation policies and procedures in clinical neuropsychology postdoctoral fellowship programs.

OBJECTIVE: The objectives of this study were to examine current procedures that are used to evaluate competency development in clinical neuropsychology at the postdoctoral level and to investigate policies and procedures for the management of performance that is below expectations during the postdoctoral fellowship. METHOD: Clinical neuropsychology fellowship program directors were invited via email with multiple reminders to participate in an online survey between 1/26/2023 and 3/31/2023. RESULTS: Most programs administer a competency-based written evaluation of fellow performance (92%) and have a written policy for managing performance that is below expectations (86%). However, greater variability was reported regarding the use of other evaluation tools, including fellow self-assessments (46% of programs), program evaluations (57% of programs), supervisor evaluations (73% of programs), and exit interviews (82% of programs). Moreover, there was variability between programs with regard to the specific competencies that were measured and how performance that is below expectations is managed. CONCLUSIONS: Competency-based evaluations and clear, written policies and procedures for management of performance that is below expectations are recommended. Such tools and policies provide clear expectations for fellowship outcomes, promote regular communication between fellows and supervisors, foster early identification of gaps in training, facilitate program quality improvement, and increase opportunities to support and intervene during the course of fellowship training.

Acute clinical recovery from sport-related concussion.

Concussion is a highly prevalent injury in contact and collision sports that has historically been poorly understood. An influx of sport-concussion research in recent years has led to a dramatic improvement in our understanding of the injury's defining characteristics and natural history of recovery. In this review, we discuss the current state of knowledge regarding the characteristic features of concussion and typical acute course of recovery, with an emphasis on the aspects of functioning most commonly assessed by clinicians and researchers (e.g., symptoms, cognitive deficits, postural stability). While prototypical clinical recovery is becoming better understood, questions remain regarding what factors (e.g., injury severity, demographic variables, history of prior concussions, psychological factors) may explain individual variability in recovery. Although research concerning individual differences in response to concussion is relatively new, and in many cases limited methodologically, we discuss the evidence about several potential moderators of concussion recovery and point out areas for future research. Finally, we describe how increased knowledge about the negative effects of and recovery following concussion has been translated into clinical guidelines for managing concussed athletes.

Language lateralization by fMRI and Wada testing in 229 patients with epilepsy: rates and predictors of discordance.

PURPOSE: To more definitively characterize Wada/functional magnetic resonance imaging (fMRI) language dominance discordance rates with the largest sample of patients with epilepsy to date, and to examine demographic, clinical, and methodologic predictors of discordance. METHODS: Two hundred twenty-nine patients with epilepsy underwent both a standardized Wada test and a semantic decision fMRI language protocol in a prospective research study. Language laterality indices were computed for each test using automated and double-blind methods, and Wada/fMRI discordance rates were calculated using objective criteria for discordance. Regression analyses were used to explore a range of variables that might predict discordance, including subject variables, Wada quality indices, and fMRI quality indices. KEY FINDINGS: Discordant results were observed in 14% of patients. Discordance was highest among those categorized by either test as having bilateral language. In a multivariate model, the only factor that predicted discordance was the degree of atypical language dominance on fMRI. SIGNIFICANCE: fMRI language lateralization is generally concordant with Wada testing. The degree of rightward shift of language dominance on fMRI testing is strongly correlated with Wada/fMRI discordance, suggesting that fMRI may be more sensitive than Wada to right hemisphere language processing, although the clinical significance of this increased sensitivity is unknown. The relative accuracy of fMRI versus Wada testing for predicting postsurgical language outcome in discordant cases remains a topic for future research.

Naming outcome prediction in patients with discordant Wada and fMRI language lateralization.

OBJECTIVE: Investigations of the validity of fMRI as an alternative to Wada language testing have yielded Wada/fMRI discordance rates of approximately 15%, but almost nothing is known regarding the relative accuracy of Wada and fMRI in discordant cases. The objective of this study was to determine which of the two (the Wada test or the language fMRI) is more predictive of postoperative naming outcome following left anterior temporal lobectomy in discordant cases. METHODS: Among 229 patients with epilepsy who prospectively underwent Wada and fMRI language testing, ten had discordant language lateralization results, underwent left anterior temporal lobectomy, and returned for postoperative language testing. The relative accuracy of Wada and fMRI for predicting language outcome was examined in these cases. RESULTS: Functional magnetic resonance imaging provided a more accurate prediction of language outcome in seven patients, Wada was more accurate in two patients, and the two tests were equally accurate in one patient. CONCLUSIONS: In cases of discordance, fMRI predicted postsurgical naming outcome with relatively better accuracy compared to the Wada test.

Naming outcome after left or right temporal lobectomy in patients with bilateral language representation by Wada testing.

OBJECTIVE: This study aimed to examine language outcome after left or right anterior temporal lobectomy (ATL) in patients with epilepsy with bilateral language representation on intracarotid sodium amobarbital (Wada) testing. METHODS: Twenty-two patients with epilepsy with bilateral language (Wada laterality index between -50 and 50) underwent right ATL (RATL, n=10) or left ATL (LATL, n=12). All the patients were administered the Boston Naming Test preoperatively and six months postoperatively. RESULTS: Left anterior temporal lobectomy patients showed greater postoperative naming decline than RATL patients. Group differences were also observed on subtests of the Wada test. Performance on the Wada naming and comprehension subtests was better in the nonsurgical hemisphere than in the surgical hemisphere in the RATL group, but there was no difference between the nonsurgical and the surgical hemisphere naming and comprehension performance in the LATL group. CONCLUSIONS: Left anterior temporal lobectomy patients with bilateral language are at greater risk for naming decline than RATL patients with bilateral language. This difference may be due to relatively better naming and comprehension abilities in the nonsurgical hemisphere in the RATL group.

Competency-based assessment in clinical neuropsychology at the post-doctoral level: Stages, milestones, and benchmarks as proposed by an APPCN work group.

Objective: In recent years, there has been considerable progress in developing competencies in Clinical Neuropsychology. The field also needs to work towards consistency in competency-based assessment of the development of each competency to ensure competent, independent practice. The purpose of this manuscript is to a) document the relevant literature, b) describe the process applied by an Association of Post-Doctoral Programs in Clinical Neuropsychology (APPCN) workgroup on Competency-Based Assessment, and c) propose a framework and assessment tool for competency-based assessment at the post-doctoral training level. Methods: The work group conducted a literature review of competency-based assessment in Clinical Neuropsychology and related fields, considered various constructs for assessment, delineated a framework that can be flexible for program-specific goals, and created a tool for assessment. The workgroup then asked for review of the framework and assessment tool by APPCN Board of Directors, the APPCN Executive Committee, and Program Directors from APPCN and non-APPCN programs. Revisions were made following this review. Conclusions: This manuscript and proposed assessment tool invite constructive feedback within the community for ongoing evolution of the process and the tool. The proposed assessment tool is intended to be implemented flexibly within post-doctoral programs to respect their specific training goals while simultaneously providing underlying consistency in the method of assessing a recently proposed set of competencies within Clinical Neuropsychology. Creation of competency-based assessment tools across all training levels within Clinical Neuropsychology that facilitate continuity and hierarchical development is a long-term goal.

Cognitive and functional outcomes following a traumatic brain injury sustained 22 years after epilepsy surgery: A case report.

Anterior temporal lobectomy (ATL) is an effective treatment for drug-resistant epilepsy, and risk for post-surgical naming and verbal memory decline after dominant hemisphere ATL is well-established. However, less is known about later life cognitive and functional outcomes following ATL performed in early or mid-life, as there are few studies that report very long-term outcomes, and the intersection of epilepsy and the aging process is not well-understood. Factors that may promote healthy cognitive aging or confer increased risk for cognitive decline in late life for those with seizure onset in early or mid-life have yet to be determined. This case report describes an individual with drug-resistant epilepsy who was treated with left ATL in mid-life, and then subsequently sustained a moderate traumatic brain injury 22 years later. The excellent recovery and remarkable stability of cognitive performance over time may be associated with several protective factors such as favorable seizure outcome, high cognitive reserve, and the absence of co-occurring medical conditions. This case also highlights the clinical utility of serial neuropsychological testing at multiple timepoints across the lifespan for those with epilepsy, and the importance of considering the clinical significance, or functional impact, of cognitive deficits in this population.

Integration of neuropsychology services in a sickle cell clinic and subsequent healthcare use for pain crises.

Objective: Growing literature has documented the clinical utility of neuropsychological evaluations for predicting functional outcomes, including reduced healthcare service utilization, in a variety of clinical samples. The present study investigates the relationship between the integration of clinical neuropsychology services into an existing outpatient sickle cell clinic and frequency of emergency department (ED) visits and hospitalizations for pain crises. Method: Participants included 144 adults diagnosed with sickle cell disease (SCD) who either underwent neuropsychological evaluation (NP+), including interview, neuropsychological testing, and feedback, or treatment as usual (NP-). Medical records were reviewed for a two-year period, one year prior to study enrollment (pre-assessment) and one year post-study enrollment (post-assessment), to track the number of ED visits and hospitalizations related to sickle cell pain crises. Results: When examining pain crises ED visits prior to and following neuropsychological evaluation, there was a significant decrease in ED visits for the NP + group, but no change for the NP - group. No significant changes in pain crises hospitalizations were observed for the NP + and NP - groups. For the NP + group, the decreased incidence of pain crises ED visits and hospitalizations was associated with an estimated total cost savings of $994,821. Discussion: Results highlight that integration of neuropsychology services into an existing outpatient sickle cell clinic may reduce healthcare costs, particularly use of pain crises ED services, for adults with SCD.

Performance validity testing in a clinical sample of adults with sickle cell disease.

OBJECTIVE: Neuropsychologists utilize performance validity tests (PVTs) as objective means for drawing inferences about performance validity. The Test of Memory Malingering (TOMM) is a well-validated, stand-alone PVT and the Reliable Digit Span (RDS) and Reliable Digit Span-Revised (RDS-R) from the Digit Span subtest of the WAIS-IV are commonly employed, embedded PVTs. While research has demonstrated the utility of these PVTs with various clinical samples, no research has investigated their use in adults with sickle cell disease (SCD), a condition associated with multiple neurological, physical, and psychiatric symptoms. Thus, the purpose of this study was to explore PVT performance in adults with SCD. METHOD: Fifty-four adults with SCD (Mage = 40.61, SD = 12.35) were consecutively referred by their hematologist for a routine clinical outpatient neuropsychological evaluation. During the evaluation, participants were administered the TOMM (Trials 1 and 2), neuropsychological measures including the WAIS-IV Digit Span subtest, and mood and behavioral questionnaires. RESULTS: The average score on the TOMM was 47.70 (SD = 3.47, range = 34-50) for Trial 1 and 49.69 (SD = 1.66, range = 38-50) for Trial 2. Only one participant failed Trial 2 of the TOMM, yielding a 98.1% pass rate for the sample. Pass rates at various RDS and RDS-R values were calculated with TOMM Trial 2 performance as an external criterion. CONCLUSIONS: Results support the use of the TOMM as a measure of performance validity for individuals with SCD, while RDS and RDS-R should be interpreted with caution in this population.

Sensitivity and specificity of memory and naming tests for identifying left temporal-lobe epilepsy.

The sensitivity and specificity of the Selective Reminding Test (SRT) Delayed Recall, Wechsler Memory Scale (WMS) Logical Memory, the Boston Naming Test (BNT), and two nonverbal memory measures for detecting lateralized dysfunction in association with side of seizure focus was examined in a sample of 143 patients with left or right temporal-lobe epilepsy (TLE). Scores on the SRT and BNT were statistically significantly lower in the left TLE group compared with the right TLE group, whereas no group differences emerged on the Logical Memory subtest. No significant group differences were found with nonverbal memory measures. When the SRT and BNT were both entered as predictors in a logistic regression, the BNT, although significant, added minimal value to the model beyond the variance accounted for by the SRT Delayed Recall. Both variables emerged as significant predictors of side of seizure focus when entered into separate regressions. Sensitivity and specificity of the SRT and BNT ranged from 56% to 65%. The WMS Logical Memory and nonverbal memory measures were not significant predictors of the side of seizure focus.

Predictors of language lateralization in temporal lobe epilepsy.

Among patients with epilepsy, atypical (rightward) language lateralization has been associated with left-handedness, a left seizure focus, an early age at seizure onset, and familial sinistrality, although these associations are not consistently observed. No study has examined all of these factors in relation to language lateralization in the same epilepsy sample, let alone in a sample comprised only of patients with temporal lobe epilepsy. Moreover, little consideration has been given in previous studies to how language lateralization might be influenced by the interplay between different factors, or how much unique variance in language lateralization is explained by each factor. The primary aim of this study was to examine the combined influences of handedness, side of seizure focus, age at seizure onset, and familial sinistrality on language lateralization in temporal lobe epilepsy patients. A secondary aim was to determine which factors uniquely contribute to the prediction of language lateralization. 162 patients with intractable temporal lobe epilepsy underwent functional MRI language mapping, from which language lateralization indexes were derived. Degree of handedness was measured via the Edinburgh Handedness Inventory. Main and 2-way interaction effects on language lateralization indexes were examined via linear regressions and Fisher exact tests. Significant effects were next examined in multiple regressions to identify unique predictors of language lateralization indexes. When examined in isolation in regressions, only left-handedness and a left seizure focus predicted atypical (rightward) language lateralization. These results, however, were qualified by interaction effects demonstrating that stronger left hand preference was associated with greater atypical language lateralization only among patients with a left seizure focus, an early or intermediate age at seizure onset, or no familial sinistrality. In follow-up multiple regressions, the interaction terms accounted for a significant amount of variance in language lateralization indexes above and beyond main effects. Additionally, side of seizure focus and its interaction with handedness uniquely predicted language lateralization indexes. Results indicate that degree of left-handedness is a marker of greater atypical (rightward) language lateralization in temporal lobe epilepsy but only in the context of seizure characteristics that have the potential to drive joint reorganization of language and hand preference (i.e., left seizure focus, or early or intermediate age at seizure onset) or in the absence of a genetic predisposition for left-handedness (i.e., no familial sinistrality). This study advances existing knowledge by illustrating how different factors combine to jointly affect language lateralization, and by identifying side of seizure focus and its interaction with handedness as unique predictors of language lateralization in temporal lobe epilepsy.