The neuropsychological presentation of women with epilepsy: clinical considerations and future directions.

Objective: Cognitive, mood, and behavioral changes are common among persons with epilepsy (PWE), resulting in a complex neuropsychological presentation. Women with epilepsy (WWE) represent a distinct cohort within the broader epilepsy population due to sex and gender-specific factors impacting epilepsy semiology and treatment. However, unique neuropsychological profiles among WWE have not been established. This narrative review aims to further define neuropsychological correlates in WWE and promote meaningful discussion related to enhancing the provision of neuropsychological care within this clinical population. Method: Current literature in PWE examining differences in cognitive function, mental health, and quality of life (QoL) between women and men was critically reviewed, emphasizing considerations for neuropsychological practice. Results: WWE demonstrate a preservation of verbal learning and memory compared to men both pre- and post-surgically, with sex-based, neurobiological mechanisms likely contributing to this association. WWE also have elevated risk for affective disorder psychopathology, suicidality, and traumatic experiences. Epidemiology related to psychotic and bipolar spectrum disorders is less clear, and findings are mixed regarding sex-specific behavioral side effects of antiseizure and psychotropic medication. Finally, hormonal and obstetric factors are highlighted as important contributors to neuropsychological symptoms in WWE, with elevated risk for low QoL and increased stigma associated with greater medical and psychiatric comorbidities compared to men. Conclusions: While emerging literature has begun to characterize the neuropsychological presentation of WWE, future research is needed to define sex and gender differences in neuropsychological sequalae among PWE to ensure consistency and quality of care for WWE.

Cognitive "success" in the setting of performance validity test failure.

BACKGROUND: Although studies have shown unique variance contributions from performance invalidity, it is difficult to interpret the meaning of cognitive data in the setting of performance validity test (PVT) failure. The current study aimed to examine cognitive outcomes in this context. METHOD: Two hundred and twenty-two veterans with a history of mild traumatic brain injury referred for clinical evaluation completed cognitive and performance validity measures. Standardized scores were characterized as Within Normal Limits (≥16th normative percentile) and Below Normal Limits (<16th percentile). Cognitive outcomes are examined across four commonly used PVTs. Self-reported employment and student status were used as indicators of "productivity" to assess potential functional differences related to lower cognitive performance. RESULTS: Among participants who performed in the invalid range on Test of Memory Malingering trial 1, Word Memory Test, Wechsler Adult Intelligence Scale-Fourth Edition Digit Span aged corrected scaled score, and the California Verbal Learning Test-Second Edition Forced Choice index, 16-88% earned broadly within normal limits scores across cognitive testing. Depending on which PVT measure was applied, the average number of cognitive performances below the 16th percentile ranged from 5 to 7 of 14 tasks. There were no differences in the total number of below normal limits performances on cognitive measures between "productive" and "non-productive" participants (T = 1.65, p = 1.00). CONCLUSIONS: Results of the current study suggest that the range of within normal limits cognitive performance in the context of failed PVTs varies greatly. Importantly, our findings indicate that neurocognitive data may still provide important practical information regarding cognitive abilities, despite poor PVT outcomes. Further, given that rates of below normal limits cognitive performance did not differ among "productivity" groups, results have important implications for functional abilities and recommendations in a clinical setting.

Embedded cognitive and emotional/affective self-reported symptom validity indices on the patient competency rating scale.

OBJECTIVE: Although there is an abundance of research on stand-alone and embedded performance validity tests and stand-alone symptom validity tests (SVTs), less emphasis has been placed on embedded SVTs. The goal of the current study was to examine the ability of embedded indicators within the Patient Competency Rating Scale (PCRS) to separately detect invalid cognitive and/or emotional/affective symptom responding. METHOD: Participants included 299 veterans assessed in a VA medical center epilepsy monitoring unit from 2013-2017 (mean age = 48.8 years, SD = 13.5 years). Two SVT composites were created; self-reported cognitive symptom validity (SVT-C) and self-reported emotional/affective symptom validity (SVT-E). Groups were compared on PCRS total and index scores (i.e., cognitive, activities of daily living, emotional, and interpersonal competencies) using ANOVAs. Receiver operating characteristic (ROC) curve analyses assessed the classification accuracy of the PCRS total and index scores for SVT-C and SVT-E. RESULTS: In ANOVAs, SVT-C was significantly associated with all PCRS indices, while SVT-E was only significantly associated with the PCRS total, emotional, and interpersonal competency indices. Although the PCRS-T ≤ 90 had the strongest classification of SVT-C and SVT-E (specificities: .90, sensitivities: .44 to .50), PCRS index scores showed suggestive evidence of domain specificity, with PCRS-ADL ≤22, PCRS-C ≤ 20, and PCRS-CADL ≤45 best classifying SVT-C (specificities: .92, sensitivities: .33) and the PCRS-E ≤ 18 best classifying the SVT-E group (specificity: .93, sensitivity: .40). CONCLUSION: Results suggest the PCRS may be used to obtain clinically useful information while including embedded indicators that can assess cognitive and/or emotional/affective symptom invalidity.

Characterizing differences in psychiatric profiles between male and female veterans with epilepsy and psychogenic non-epileptic seizures.

OBJECTIVE: While previous studies have described psychiatric profiles in patients with psychogenic non-epileptic seizures (PNES) and epileptic seizures (ES), a well-matched comparison between males and females has been lacking. To address this shortcoming, the present study sought to explore sex differences between male and female Veterans with ES and PNES in terms of psychiatric diagnoses, trauma histories, and psychiatric treatment. METHODS: A male Veteran sample (PNES n = 87, ES n = 28) was identified matching age and seizure diagnosis with our previously-gathered female Veteran sample (PNES n = 90, ES n = 28). Retrospective chart review was used to obtain demographic, psychiatric, and seizure-related variables. Group differences between PNES and ES were first assessed among males followed by differences between males and females. RESULTS: Males with PNES were more likely to receive psychiatric treatment (82.6 % vs. 60.7 %, p = 0.017), be prescribed more psychotropics (1.6 vs. 0.9, p = 0.003), and more likely to have childhood physical abuse (27.9 % vs. 3.6 %, p = 0.007) than those with ES. Compared to PNES, males with ES presented to the epilepsy monitoring unit (EMU) significantly later (12.8 years vs. 6.1 years, p = 0.009), and were prescribed more anti-seizure medications (ASMs) previously (2.1 vs. 0.8, p = 0.009) and currently (1.6 vs. 1.0, p = 0.001). Between males and females with PNES, females evidenced more depression (76.7 % vs. 26.3 %, p < 0.001), borderline personality disorder (18.9 % vs. 4.7 %, p = 0.004), suicidality (65.6 % vs. 33.7 %, p < 0.001), and childhood sexual abuse (37.8 % vs. 11.6 %, p < 0.001), while males had higher rates of substance use disorders (37.2 % vs. 8.9 %, p < 0.001). SIGNIFICANCE: A greater psychiatric burden is seen among females compared to males with PNES, especially diagnoses of borderline personality disorder and depression. Higher rates of suicidality and inpatient psychiatric hospitalization may warrant particular consideration in screening and intervention efforts among female Veterans with PNES.

Characterizing women veterans receiving seizure care in the veterans affairs healthcare system.

OBJECTIVE: The number and proportion of women served by the Veterans Health Administration (VHA) is rapidly expanding, necessitating better characterization of factors unique to this population. While nascent literature has begun to better characterize women within the broader seizure population, women Veterans remain an understudied sample. To expand our clinical understanding of women with seizures, we assessed demographic and clinical characteristics, as well as psychiatric/military histories in women receiving care from an Epilepsy Center of Excellence within the VA Healthcare System. METHODS: The sample included 90 women with psychogenic nonepileptic seizures (PNES) and 28 women with epileptic seizures (ES) as the final diagnosis after epilepsy monitoring at a large VA medical center between 2010 and 2020. Retrospective chart review gathered demographics, including age, marital status, and work status; clinical characteristics, including history of traumatic brain injury (TBI) or migraines, gynecological history, and use of anti-seizure medications (ASM); psychiatric information, including trauma history, psychiatric diagnoses, and treatment; and military history related to service or service connection. Group differences were assessed between women with PNES and ES. RESULTS: The ES group was significantly older than the PNES group (47.8 v. 41.9 years, p = 0.02) and had a non-significantly longer diagnosis duration (12.3 vs. 8.6 years, p = 0.17). Clinically, the PNES group had a significantly higher rate of migraines (76.7% v. 57.1%, p = 0.04) and hysterectomy (40% v. 17.9%, p = 0.03). Many psychiatric factors differentiated the two groups, with significantly higher rates of psychotropic medication use (86.7% v. 60.7%, p = 0.002), psychiatric hospitalization (42.2% v. 21.4%, p = 0.047), and suicide attempts (42.2% v. 14.3%, p = 0.005), alongside trends toward higher rates of military sexual trauma (47.8% vs. 28.6%, p = 0.07) and childhood sexual trauma (37.8% vs. 17.9%, p = 0.05) among those with PNES. SIGNIFICANCE: This is the largest study to date characterizing women veterans with seizures seeking comprehensive seizure care and provides an update to previously published information on Veteran samples with seizures. Several characteristics differ between women Veterans with PNES and ES, spanning demographic, clinical, and psychiatric factors. Understanding the unique profile of women Veterans with epilepsy seeking care through the VA system is a crucial step in providing optimal care, including making informed diagnosis and providing appropriate treatment.

The Relationship between Health Literacy and Comfort with Teleneuropsychology in a Veteran Sample.

OBJECTIVE: Health literacy is a strong psychosocial determinant of health disparities and has been found to relate to various aspects of health-related technology use. With the increased implementation of neuropsychological services performed via telehealth during the coronavirus disease 2019 pandemic, the relationship between health literacy and comfort with teleneuropsychology warrants further investigation. METHOD: The present study examined 77 Veterans participating in neuropsychological evaluations as a part of standard clinical care. The sample was diverse in terms of age ethnicity, and psychiatric and neurocognitive diagnoses. In addition to a fixed-flexible neuropsychological battery, the Brief Health Literacy Screening Tool (BRIEF) was administered to evaluate health literacy. Self-reported comfort with the teleneuropsychological evaluation was assessed using an informal 10-point scale, and qualitative comfort responses were also recorded. RESULTS: Independent samples t-tests revealed older adults were more likely to participate in the evaluation via telephone than with VA Video Connect. Although health literacy was not related to telehealth modality, it was correlated with comfort with the teleneuropsychological evaluation (r = .34, p < .01), although it is notable that average comfort levels were high across modalities (M = 8.16, SD = 2.50). CONCLUSIONS: Findings support the notion that teleneuropsychological services may feasibly be implemented with a diverse group of patients, although flexibility with modality may be necessary. Those performing these services should also be aware that patients with lower health literacy may feel less comfortable with teleneuropsychology as they seek to build rapport and optimize evaluation engagement.

The Severe Impairment Profile: A Conceptual Shift.

OBJECTIVE: The current study sought to evaluate and replicate the severe impairment profile (SIP) of the Word Memory Test (WMT) in patients referred for dementia evaluations. METHOD: The sample consisted of 125 patients referred for a neuropsychological evaluation at a large Veterans Affairs Medical Center. Patients were assigned a Clinical Dementia Rating (CDR) by blind raters, and were classified according to their performance on performance validity testing. Subsequent chart reviews were conducted to help in more accurately determining the presence of severe memory impairment likely due to an underlying dementing process versus poor effort/task engagement. RESULTS: In our sample, 51% of patients failed easy WMT subtests and 93% of these patients obtained the SIP. The rates of failure on these easy subtests generally coincided with both more severely impaired CDR ratings, as well as more impaired delayed memory composite scores. Upon chart review, it was determined that there were likely a significant portion of classification errors using the SIP, with a positive posttest probability of impairment based on having the SIP being 65% as opposed to 28% for a negative result. CONCLUSIONS: Our findings suggest that the SIP does not appear to function effectively in a mixed dementia sample where there is increased potential for secondary gain. Additional concern is expressed regarding the overall likelihood of obtaining the SIP and subsequent inferential decisions related to obtaining an SIP. Future research should examine more optimal cut scores or alternative methods for more accurately classifying patients in different clinical contexts and patterns of impairment.

Relative Utility of Performance and Symptom Validity Tests.

This investigation adds to the burgeoning body of research concerned with discriminating performance and symptom validity tests (SVTs) through examination of their differential relationships with cognitive performance and symptom self-report measures. To the authors' current knowledge, prior studies have not assessed differences between participants who fail either a performance validity test (PVT) or an SVT but not both. As part of their neuropsychological evaluations at four Veterans Affairs medical centers across the United States, participants were administered a fixed, standardized battery that consisted of performance validity, symptom validity, cognitive performance, and symptom self-report measures. Compared with participants who failed a PVT and an SVT, participants who passed both and participants who only passed a PVT demonstrated better cognitive performance and self-reported fewer symptoms. Results support differential clinical utility of performance validity and SVTs when assessing cognitive performance and symptom self-report.

Factors related to satisfaction with life in veterans with mild traumatic brain injury.

PURPOSE/OBJECTIVE: Satisfaction with life (SWL) is an important measure of outcome in rehabilitation. Previous research suggests that those with a history of traumatic brain injury (TBI), even mild TBI, report lower levels of life satisfaction when compared with the noninjured population. Although is it possible that TBI has a direct effect on SWL, various medical and psychosocial factors commonly affecting those recovering from TBI likely contribute to SWL. RESEARCH METHOD/DESIGN: The present study aimed to identify factors related to SWL in 95 veterans of Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) with a history of mild TBI. RESULTS: Regression analyses indicated that headache impact, pain interference, sleep quality, posttraumatic stress symptom severity, and social support were all significantly related to SWL. However, when secondary analyses were conducted including posttraumatic stress symptom severity as a covariate before the entry of other predictors, only sleep quality and social support remained significantly associated with SWL. CONCLUSIONS/IMPLICATIONS: These results indicate the importance of properly identifying and treating symptoms of posttraumatic stress in veterans with a history of mTBI, as posttraumatic stress symptoms appear to be strongly related to SWL in those with a history of mild TBI. Optimizing sleep quality and social support may also be important in improving SWL.

Clinician versus Veteran ratings on the Mayo-Portland Participation Index in veterans with a history of mild traumatic brain injury.

BACKGROUND: The Department of Veterans Affairs is encouraging administration of the Mayo-Portland Adaptability Inventory-4 Participation Index (M2PI) to identify long-term psychosocial outcomes of Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) Veterans with a history of traumatic brain injury (TBI). OBJECTIVE: To evaluate clinician and Veteran interrater reliability and how response validity influences M2PI item ratings. PARTICIPANTS: A total of 122 OEF/OIF/OND Veterans who reported a history consistent with mild TBI during deployment and were referred for neuropsychological evaluation following Comprehensive TBI Evaluation. DESIGN: Interrater reliability study. MAIN MEASURES: M2PI; Minnesota Multiphasic Personality Inventory-2 Symptom Validity Scale (FBS). RESULTS: Veterans reported greater perceived restrictions than clinicians across all M2PI items and total score. Interrater correlations ranged from rs = 0.27 (residence) to rs = 0.58 (money management) across items, with a total score correlation of rs = 0.60. When response bias was indicated, both Veterans and clinicians reported greater participation restrictions than those reported by Veterans without evidenced response bias. CONCLUSION: Low interrater correlation is consistent with previous findings. As ratings of clinicians and Veterans should not be interpreted as equivalent, documenting the rater's identity is important for interpretation. Using objective indicators of functional outcome may assist clinician raters, particularly when self-report may be biased.

The dangers of failing one or more performance validity tests in individuals claiming mild traumatic brain injury-related postconcussive symptoms.

Evaluating performance validity is important in any neuropsychological assessment, and prior research recommends a threshold for invalid performance of two or more performance validity test (PVT) failures. However, extant findings also indicate that failing a single PVT is associated with significant changes in neuropsychological performance. The current study sought to determine if there is an appreciable difference in neuropsychological testing results between individuals failing different numbers of PVTs. In a sample of veterans with reported histories of mild traumatic brain injury (mTBI; N =178), analyses revealed that individuals failing only one PVT performed significantly worse than individuals failing no PVTs on measures of verbal learning and memory, processing speed, and cognitive flexibility. Additionally, individuals failing one versus two PVTs significantly differed only on delayed free recall scores. The current findings suggest that failure of even one PVT should elicit consideration of performance invalidity, particularly in individuals with histories of mTBI.

Ecological validity of performance validity testing.

Performance validity tests (PVTs) have been shown to relate to neuropsychological performance, but no studies have looked at the ecological validity of these measures. Data from 131 veterans with a history of mild traumatic brain injury from a multicenter Veterans Administration consortium were examined to determine the relation between scores on a self-report version of the Mayo-Portland Adaptability Inventory Participation Index, a measure of community participation, and the Word Memory Test, a PVT. A restricted regression model, including education, age, history of loss of consciousness, cognitive measures, and a measure of symptom validity test performance, was not significantly associated with self-reported community reintegration. Adding PVT results to the restricted model, however, did significantly improve the prediction of community reintegration as PVT failure was associated with lower self-reported community participation. The results of this study indicate that PVTs may also serve as an indicator of patients' functioning in the community.

PTSD and cognitive functioning: importance of including performance validity testing.

Many studies have observed an association between post-traumatic stress disorder (PTSD) and cognitive deficits across several domains including memory, attention, and executive functioning. The inclusion of response bias measures in these studies, however, remains largely unaddressed. The purpose of this study was to identify possible cognitive impairments correlated with PTSD in returning OEF/OIF/OND veterans after excluding individuals failing a well-validated performance validity test. Participants included 126 men and 8 women with a history of mild traumatic brain injury (TBI) referred for a comprehensive neuropsychological evaluation as part of a consortium of five Veterans Affairs hospitals. The PTSD CheckList (PCL) and Word Memory Test (WMT) were used to establish symptoms of PTSD and invalid performance, respectively. Groups were categorized as follows: Control (PCL < 50, pass WMT), PTSD-pass (PCL ≥ 50, pass WMT), and PTSD-fail (PCL ≥ 50, fail WMT). As hypothesized, failure on the WMT was associated with significantly poorer performance on almost all cognitive tests administered; however, no significant differences were detected between individuals with and without PTSD symptoms after separating out veterans failing the WMT. These findings highlight the importance of assessing respondent validity in future research examining cognitive functioning in psychiatric illness and warrant further consideration of prior studies reporting PTSD-associated cognitive deficits.

The relation of depression and anxiety to measures of executive functioning in a mixed psychiatric sample.

The relationship between mood and executive functioning is of particular importance to neuropsychologists working with mixed psychiatric samples. The present study evaluated the relation of self-reported depression and anxiety to several common measures of executive functioning: the Wisconsin Card Sorting Test, the Trail Making Test, the Controlled Oral Word Association, and the Letter-Number Sequencing subtest of the Weschler Adult Intelligence Scale-III. Records from 86 adult patients evaluated in an outpatient psychiatry unit were examined. Correlations between self-reported depression or anxiety and most measures of executive functioning were small and non-significant. The variance predicted by depression or anxiety after controlling for age, gender, and IQ was minimal (typically < or =3.0%), even after conducting diagnostic subgroup analyses. These results suggest that impaired performance on measures of executive functioning is minimally related to self-reported depression and anxiety within mixed psychiatric settings.

A new euglobulin clot lysis assay for global fibrinolysis.

Plasma fibrinolytic activity has been measured by the euglobulin clot lysis time (ELT) since the late 1950s. The euglobulin clot lysis assay (ECLA) method has been modified using a computerized kinetic spectrophotometric microtiter plate reader and measures optical density changes of recalcified euglobulin fraction of plasma samples over time. This method has been applied to normal healthy adults, children, pregnant women and newborn infants, which represent physiologic extremes of the ELT. The ECLA method adds measurements of maximum absorbance (Max Abs), area under the curve (AUC) and mean velocity to the standard clot lysis time. The resulting curves are unique to this method and have been analyzed and compared in order to establish normal ranges. Fibrinogen levels, plasminogen activator inhibitor-1 (PAI-1) antigen, PAI-1 activity and thrombin activatable fibrinolytic inhibitor (TAFI) antigen levels were measured in each individual of the four groups. Each protein measured within each study group except TAFI correlated with the lysis time, maximum absorbance and area under the curve. Considering all four groups together, PAI correlates most highly with lysis time, fibrinogen correlates the highest with Max Abs; fibrinogen and PAI-1 antigen have equally high correlations to AUC. Area under the curve is highly correlated with all coagulation parameters measured; the most significant contributor is fibrinogen. These observations are interesting, but at this time, it cannot be said that any of the test parameters are better than lysis time in distinguishing between these normal physiologic states.