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The memory assessment clinics scale for epilepsy (MAC-E): A brief measure of subjective cognitive complaints in epilepsy

Miller, Margaret; Honomichl, Ryan; Lapin, Brittany; Hogan, Thomas; Thompson, Nicholas; Barr, William B; Friedman, Daniel; Sieg, Erica; Schuele, Stephan; Kurtish, Selin Yagci; Özkara, Cigdem; Lin, Katia; Wiebe, Samuel; Jehi, Lara; Busch, Robyn M
PMID: 33106081
ISSN: 1744-4144
CID: 5287482

Handedness and Cognition in Multiple Sclerosis: Potential Indications for Hemispheric Vulnerability

Miller, Jennifer R; Altaras, Caroline; Zemon, Vance; Barr, William B; Weinberger, Andrea H; Foley, Frederick W
BACKGROUND:Multiple sclerosis (MS) affects over 2.5 million individuals worldwide, yet much of the disease course is unknown. Hemispheric vulnerability in MS may elucidate part of this process but has not yet been studied. The current study assessed neuropsychological functioning as it relates to hemispheric vulnerability in MS. METHODS:Verbal IQ, as measured by verbal comprehension index (VCI), nonverbal IQ, as measured by perceptual reasoning index (PRI) and memory acquisition were compared in right-handed (dextral) and non-right-handed (non-dextral) persons with MS (PwMS). RESULTS:Linear mixed-effects modeling indicated a significant main effect of handedness, F(1, 195.35) = 3.95, p = .048, for a composite measure of VCI, PRI, and memory acquisition, with better performance for dextral PwMS. In examining differences for specific neuropsychological measures, the largest effect size between dextral and non-dextral participants was seen in PRI (d = 0.643), F(1,341) = 12.163, p = .001. No significant interaction effect between handedness and IQ was found, F(3, 525.60) = 0.75, p = .523. CONCLUSIONS:Dextral PwMS perform better than non-dextral PwMS when assessing neuropsychological performance for memory and IQ combined. Results are suggestive of increased vulnerability in the left brain to the pathological process of MS.
PMID: 35284930
ISSN: 1873-5843
CID: 5183752

Cognitive phenotypes in frontal lobe epilepsy

Arrotta, Kayela; Reyes, Anny; Kaestner, Erik; McDonald, Carrie R; Hermann, Bruce P; Barr, William B; Sarmey, Nehaw; Sundar, Swetha; Kondylis, Efstathios; Najm, Imad; Bingaman, William; Busch, Robyn M
OBJECTIVE:Neuropsychological profiles are heterogeneous both across and within epilepsy syndromes, but especially in frontal lobe epilepsy (FLE), which has complex semiology and epileptogenicity. This study aimed to characterize the cognitive heterogeneity within FLE by identifying cognitive phenotypes and determining their demographic and clinical characteristics. METHOD/METHODS:One hundred and six patients (age 16-66; 44% female) with FLE completed comprehensive neuropsychological testing, including measures within five cognitive domains: language, attention, executive function, processing speed, and verbal/visual learning. Patients were categorized into one of four phenotypes based on the number of impaired domains. Patterns of domain impairment and clinical and demographic characteristics were examined across phenotypes. RESULTS:Twenty-five percent of patients met criteria for the Generalized Phenotype (impairment in at least four domains), 20% met criteria for the Tri-Domain Phenotype (impairment in three domains), 36% met criteria for the Domain-Specific Phenotype (impairment in one or two domains), and 19% met criteria for the Intact Phenotype (no impairment). Language was the most common domain-specific impairment, followed by attention, executive function, and processing speed. In contrast, learning was the least impacted cognitive domain. The Generalized Phenotype had fewer years of education compared to the Intact Phenotype, but otherwise, there was no differentiation between phenotypes in demographic and clinical variables. However, qualitative analysis suggested that the Generalized and Tri-Domain Phenotypes had a more widespread area of epileptogenicity, whereas the Intact Phenotype most frequently had seizures limited to the lateral frontal region. SIGNIFICANCE/CONCLUSIONS:This study identified four cognitive phenotypes in FLE that were largely indistinguishable in clinical and demographic features, aside from education and extent of epileptogenic zone. These findings enhance our appreciation of the cognitive heterogeneity within FLE and provide additional support for the development and use of cognitive taxonomies in epilepsy.
PMID: 35429174
ISSN: 1528-1167
CID: 5219182

Investigating the association between subjective and objective performance-based cognitive function among former collegiate football players

Bryant, Andrew M; Kerr, Zachary Y; Walton, Samuel R; Barr, William B; Guskiewicz, Kevin M; McCrea, Michael A; Brett, Benjamin L
OBJECTIVE/UNASSIGNED:Studies have observed variable associations of prior contact sport participation with subjective and objective measures of cognitive function. This study directly investigated the association between subjective self-report and objective performance-based cognition among former collegiate football players, as well as its relationship to self-reported concussion history. METHODS/UNASSIGNED: = 1.49]) retired from sport 15-years prior were enrolled. Linear regression models examined associations between subjective cognition (Quality of Life in Neurological Disorders Cognitive Functioning-Short Form), and performance on a neuropsychological battery. Domain specific (executive function) metrics of subjective (Behavior Rating Inventory of Executive Function-Adult) and objective cognition were also exclusively examined. Associations between self-reported concussion history with subjective and objective measures were tested. Potential influential factors (sleep quality and distress) were included as covariates. RESULTS/UNASSIGNED:= .033). CONCLUSIONS/UNASSIGNED:Reliance on self-reported measures of cognitive functioning alone is insufficient when assessing cognition in former contact sport athletes. Assessment of other factors known to influence subjective cognitive complaints should also be examined in determining the presence of cognitive deficits.
PMID: 35670306
ISSN: 1744-4144
CID: 5283112

Development and application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE): Initial results from a multi-center study of adults with temporal lobe epilepsy

McDonald, Carrie R; Busch, Robyn M; Reyes, Anny; Arrotta, Kayela; Barr, William; Block, Cady; Hessen, Erik; Loring, David W; Drane, Daniel L; Hamberger, Marla J; Wilson, Sarah J; Baxendale, Sallie; Hermann, Bruce P
OBJECTIVE:and to assess the ability of the IC-CoDE to produce definable and stable cognitive phenotypes in a large, multi-center temporal lobe epilepsy (TLE) patient sample. METHOD/METHODS:were derived across samples using the IC-CoDE and compared to distributions of phenotypes reported in existing studies. RESULTS:Impairment rates were highest on tests of language, followed by memory, executive functioning, attention/processing speed, and visuospatial ability. Application of the IC-CoDE using varying operational definitions of impairment (≤ 1.0 and ≤ 1.5 SD) produced cognitive phenotypes with the following distribution: cognitively intact (30%-50%), single-domain (26%-29%), bi-domain (14%-19%), and generalized (10%-22%) impairment. Application of the ≤ 1.5 cutoff produced a distribution of phenotypes that was consistent across cohorts and approximated the distribution produced using data-driven approaches in prior studies. CONCLUSIONS:The IC-CoDE is the first iteration of a classification system for harmonizing cognitive diagnostics in epilepsy research that can be applied across neuropsychological tests and TLE cohorts. This proof-of-principle study in TLE offers a promising path for enhancing research collaborations globally and accelerating scientific discoveries in epilepsy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
PMID: 35084879
ISSN: 1931-1559
CID: 5171882

Religious conversion in an older male with longstanding epilepsy [Case Report]

Barr, William B; Liu, Anli; Laduke, Casey; Nadkarni, Siddhartha; Devinsky, Orrin
Religious experiences in epilepsy patients have provoked much interest with suggestions that hyperreligiosity is associated with temporal lobe seizures. Extreme varieties of religious behavior may be more frequent in epilepsy patients during ictal activity or during post-ictal psychotic episodes. We report a 75 year-old man with epilepsy who developed a progressive decline in cognition and behavior following a religious conversion 15 years earlier. He subsequently developed religious delusions of increasing severity and symptoms of Capgras syndrome. Brain imaging revealed bilateral posterior cortical atrophy, chronic right parieto-occipital encephalomalacia, and right mesial temporal sclerosis. Electroencephalograms and neuropsychological testing revealed initial right temporal lobe abnormalities followed by progressive frontal and bilateral dysfunction. The case highlights how a history of seizures, superimposed on sensory deprivation and a progressive impairment of right posterior and bilateral anterior brain function, may have contributed to religious conversion, which was followed by dementia and delusions involving religious content.
PMID: 35528136
ISSN: 2589-9864
CID: 5214052

Remote Memory in Epilepsy: Assessment, Impairment, and Implications Regarding Hippocampal Function

Rastogi, Sanya; Meador, Kimford J; Barr, William B; Devinsky, Orrin; Leeman-Markowski, Beth A
Studies of epilepsy patients provide insight into the neuroscience of human memory. Patients with remote memory deficits may learn new information but have difficulty recalling events from years past. The processes underlying remote memory impairment are unclear and likely result from the interaction of multiple factors, including hippocampal dysfunction. The hippocampus likely has a continued role in remote semantic and episodic memory storage over time, and patients with mesial temporal lobe epilepsy (TLE) are at particular risk for deficits. Studies have focused on lateralization of remote memory, often with greater impairment in left TLE, which may relate to verbal task demands. Remote memory testing is restricted by methodological limitations. As a result, deficits have been difficult to measure. This review of remote memory focuses on evidence for its underlying neurobiology, theoretical implications for hippocampal function, and methodological difficulties that complicate testing in epilepsy patients.
PMID: 35463127
ISSN: 1664-2295
CID: 5217232

Developing methods to detect and diagnose chronic traumatic encephalopathy during life: rationale, design, and methodology for the DIAGNOSE CTE Research Project

Alosco, Michael L; Mariani, Megan L; Adler, Charles H; Balcer, Laura J; Bernick, Charles; Au, Rhoda; Banks, Sarah J; Barr, William B; Bouix, Sylvain; Cantu, Robert C; Coleman, Michael J; Dodick, David W; Farrer, Lindsay A; Geda, Yonas E; Katz, Douglas I; Koerte, Inga K; Kowall, Neil W; Lin, Alexander P; Marcus, Daniel S; Marek, Kenneth L; McClean, Michael D; McKee, Ann C; Mez, Jesse; Palmisano, Joseph N; Peskind, Elaine R; Tripodis, Yorghos; Turner, Robert W; Wethe, Jennifer V; Cummings, Jeffrey L; Reiman, Eric M; Shenton, Martha E; Stern, Robert A
BACKGROUND:Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the "Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project." The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine and validate clinical research diagnostic criteria (i.e., traumatic encephalopathy syndrome [TES]); examine repetitive head impact exposure, genetic, and other risk factors; and provide shared resources of anonymized data and biological samples to the research community. In this paper, we provide a detailed overview of the rationale, design, and methods for the DIAGNOSE CTE Research Project. METHODS:The targeted sample and sample size was 240 male participants, ages 45-74, including 120 former professional football players, 60 former collegiate football players, and 60 asymptomatic participants without a history of head trauma or participation in organized contact sports. Participants were evaluated at one of four U.S. sites and underwent the following baseline procedures: neurological and neuropsychological examinations; tau and amyloid positron emission tomography; magnetic resonance imaging and spectroscopy; lumbar puncture; blood and saliva collection; and standardized self-report measures of neuropsychiatric, cognitive, and daily functioning. Study partners completed similar informant-report measures. Follow-up evaluations were intended to be in-person and at 3 years post-baseline. Multidisciplinary diagnostic consensus conferences are held, and the reliability and validity of TES diagnostic criteria are examined. RESULTS:Participant enrollment and all baseline evaluations were completed in February 2020. Three-year follow-up evaluations began in October 2019. However, in-person evaluation ceased with the COVID-19 pandemic, and resumed as remote, 4-year follow-up evaluations (including telephone-, online-, and videoconference-based cognitive, neuropsychiatric, and neurologic examinations, as well as in-home blood draw) in February 2021. CONCLUSIONS:Findings from the DIAGNOSE CTE Research Project should facilitate detection and diagnosis of CTE during life, and thereby accelerate research on risk factors, mechanisms, epidemiology, treatment, and prevention of CTE. TRIAL REGISTRATION:NCT02798185.
PMID: 34384490
ISSN: 1758-9193
CID: 5004422

Addressing neuropsychological diagnostics in adults with epilepsy: Introducing the International Classification of Cognitive Disorders in Epilepsy: The IC CODE Initiative

Norman, Marc; Wilson, Sarah J; Baxendale, Sallie; Barr, William; Block, Cady; Busch, Robyn M; Fernandez, Alberto; Hessen, Erik; Loring, David W; McDonald, Carrie R; Hermann, Bruce P
This paper addresses the absence of an international diagnostic taxonomy for cognitive disorders in patients with epilepsy. Initiated through the 2020 Memorandum of Understanding between the International League Against Epilepsy and the International Neuropsychological Society, neuropsychological representatives from both organizations met to address the problem and consequences of the absence of an international diagnostic taxonomy for cognitive disorders in epilepsy, overview potential solutions, and propose specific solutions going forward. The group concluded that a classification of cognitive disorders in epilepsy, including an overall taxonomy and associated operational criteria, was clearly lacking and sorely needed. This paper reviews the advantages and shortcomings of four existing cognitive diagnostic approaches, including taxonomies derived from the US National Neuropsychology Network, DSM-V Neurocognitive Disorders, the Mild Cognitive Impairment classification from the aging/preclinical dementia literature, and the Research Domain Criteria Initiative. We propose a framework to develop a consensus-based classification system for cognitive disorders in epilepsy that will be international in scope and be applicable for clinical practice and research globally and introduce the International Classification of Cognitive Disorders in Epilepsy (IC-CODE) project.
PMID: 34033259
ISSN: 2470-9239
CID: 4907072

National Institute of Neurological Disorders and Stroke Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome

Katz, Douglas I; Bernick, Charles; Dodick, David W; Mez, Jesse; Mariani, Megan L; Adler, Charles H; Alosco, Michael L; Balcer, Laura J; Banks, Sarah J; Barr, William B; Brody, David L; Cantu, Robert C; Dams-O'Connor, Kristen; Geda, Yonas E; Jordan, Barry D; McAllister, Thomas W; Peskind, Elaine R; Petersen, Ronald C; Wethe, Jennifer V; Zafonte, Ross D; Foley, Éimear M; Babcock, Debra J; Koroshetz, Walter J; Tripodis, Yorghos; McKee, Ann C; Shenton, Martha E; Cummings, Jeffrey L; Reiman, Eric M; Stern, Robert A
OBJECTIVE:To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). METHODS:April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298). RESULTS:Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features. CONCLUSIONS:New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available.
PMID: 33722990
ISSN: 1526-632x
CID: 5232512