Faculty Bibliography

BACKGROUND:and purpose: Fatigue is among the most common persistent symptoms following post-acute sequelae of Sars-COV-2 infection (PASC). The current study investigated the potential therapeutic effects of High-Definition transcranial Direct Current Stimulation (HD-tDCS) associated with rehabilitation program for the management of PASC-related fatigue. METHODS:Seventy patients with PASC-related fatigue were randomized to receive 3 mA or sham HD-tDCS targeting the left primary motor cortex (M1) for 30 min paired with a rehabilitation program. Each patient underwent 10 sessions (2 sessions/week) over five weeks. Fatigue was measured as the primary outcome before and after the intervention using the Modified Fatigue Impact Scale (MFIS). Pain level, anxiety severity and quality of life were secondary outcomes assessed, respectively, through the McGill Questionnaire, Hamilton Anxiety Rating Scale (HAM-A) and WHOQOL. RESULTS:Active HD-tDCS resulted in significantly greater reduction in fatigue compared to sham HD-tDCS (mean group MFIS reduction of 22.11 points vs 10.34 points). Distinct effects of HD-tDCS were observed in fatigue domains with greater effect on cognitive (mean group difference 8.29 points; effect size 1.1; 95% CI 3.56-13.01; P < .0001) and psychosocial domains (mean group difference 2.37 points; effect size 1.2; 95% CI 1.34-3.40; P < .0001), with no significant difference between the groups in the physical subscale (mean group difference 0.71 points; effect size 0.1; 95% CI 4.47-5.90; P = .09). Compared to sham, the active HD-tDCS group also had a significant reduction in anxiety (mean group difference 4.88; effect size 0.9; 95% CI 1.93-7.84; P < .0001) and improvement in quality of life (mean group difference 14.80; effect size 0.7; 95% CI 7.87-21.73; P < .0001). There was no significant difference in pain (mean group difference -0.74; no effect size; 95% CI 3.66-5.14; P = .09). CONCLUSION/CONCLUSIONS:An intervention with M1 targeted HD-tDCS paired with a rehabilitation program was effective in reducing fatigue and anxiety, while improving quality of life in people with PASC.

BACKGROUND:Patterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players. METHODS:One hundred seventy male former football players (n=111 professional, n=59 college; 45-74 years) completed a neuropsychological test battery. Raw scores were converted to T-scores using age, sex, and education-adjusted normative data. A T-score ≤ 35 defined impairment. A domain was impaired if 2+ scores fell in the impaired range except for the language and visuospatial domains due to the limited number of tests. RESULTS:Most football players had subjective cognitive concerns. On testing, rates of impairments were greatest for memory (21.2% two tests impaired), especially for recall of unstructured (44.7%) versus structured verbal stimuli (18.8%); 51.8% had one test impaired. 7.1% evidenced impaired executive functions; however, 20.6% had impaired Trail Making Test B. 12.1% evidenced impairments in the attention, visual scanning, and psychomotor speed domain with frequent impairments on Trail Making Test A (18.8%). Other common impairments were on measures of language (i.e., Multilingual Naming Test [21.2%], Animal Fluency [17.1%]) and working memory (Number Span Backward [14.7%]). Impairments on our tasks of visuospatial functions were infrequent. CONCLUSIONS:In this sample of former football players (most of whom had subjective cognitive concerns), there were diffuse impairments on neuropsychological testing with verbal memory being the most frequently impaired domain.

INTRODUCTION/BACKGROUND:The presentation, risk factors, and etiologies of white matter hyperintensities (WMH) in people exposed to repetitive head impacts are unknown. We examined the burden and distribution of WMH, and their association with years of play, age of first exposure, and clinical function in former American football players. METHODS:A total of 149 former football players and 53 asymptomatic unexposed participants (all men, 45-74 years) completed fluid-attenuated inversion recovery magnetic resonance imaging, neuropsychological testing, and self-report neuropsychiatric measures. Lesion Segmentation Toolbox estimated WMH. Analyses were performed in the total sample and stratified by age 60. RESULTS:In older but not younger participants, former football players had greater total, frontal, temporal, and parietal log-WMH compared to asymptomatic unexposed men. In older but not younger former football players, greater log-WMH was associated with younger age of first exposure to football and worse executive function. DISCUSSION/CONCLUSIONS:In older former football players, WMH may have unique presentations, risk factors, and etiologies. HIGHLIGHTS/CONCLUSIONS:Older but not younger former football players had greater total, frontal, temporal, and parietal lobe white matter hyperintensities (WMH) compared to same-age asymptomatic unexposed men. Younger age of first exposure to football was associated with greater WMH in older but not younger former American football players. In former football players, greater WMH was associated with worse executive function and verbal memory.

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).

In efforts to understand the cognitive heterogeneity within and across epilepsy syndromes, cognitive phenotyping has been proposed as a new taxonomy aimed at developing a harmonized approach to cognitive classification in epilepsy. Data- and clinically driven approaches have been previously used with variability in the phenotypes derived across studies. In our study, we utilize latent profile analysis to test several models of phenotypes in a large multicentre sample of patients with temporal lobe epilepsy and evaluate their demographic and clinical profiles. For the first time, we examine the added value of replacing missing data and examine factors that may be contributing to missingness. A sample of 1178 participants met the inclusion criteria for the study, which included a diagnosis of temporal lobe epilepsy and the availability of comprehensive neuropsychological data. Models with two to five classes were examined using latent profile analysis and the optimal model was selected based on fit indices, posterior probabilities and proportion of sample sizes. The models were also examined with imputed data to investigate the impact of missing data on model selection. Based on the fit indices, posterior probability and distinctiveness of the latent classes, a three-class solution was the optimal solution. This three-class solution comprised a group of patients with multidomain impairments, a group with impairments predominantly in language and a group with no impairments. Overall, the multidomain group demonstrated a worse clinical profile and comprised a greater proportion of patients with mesial temporal sclerosis, a longer disease duration and a higher number of anti-seizure medications. The four-class and five-class solutions demonstrated the lowest probabilities of a group membership. Analyses with imputed data demonstrated that the four-class solution was the optimal solution; however, there was a weak agreement between the missing and imputed data sets for the four-Class solutions (κ = 0.288, P < 0.001). This study represents the first to use latent profile analysis to test and compare multiple models of cognitive phenotypes in temporal lobe epilepsy and to determine the impact of missing data on model fit. We found that the three-phenotype model was the most meaningful based on several fit indices and produced phenotypes with unique demographic and clinical profiles. Our findings demonstrate that latent profile analysis is a rigorous method to identify phenotypes in large, heterogeneous epilepsy samples. Furthermore, this study highlights the importance of examining the impact of missing data in phenotyping methods. Our latent profile analysis-derived phenotypes can inform future studies aimed at identifying cognitive phenotypes in other neurological disorders.

Introduction: Treatment of pediatric MS is challenging as most disease-modifying therapies (DMT) lack efficacy data in children, including switching from first-line platform DMT. Objectives/Aims: To assess real-world effectiveness of switching DMT in patients initially treated with platform injectable DMT on disease activity in pediatric MS and CIS.
Method(s): This is a cohort study of children with MS/CIS at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with platform injectable (interferon-beta, glatiramer acetate) and switched to the other class of injectable, oral (dimethyl fumarate, fingolimod, teriflunomide) or infusion (natalizumab, rituximab, ocrelizumab, alemtuzumab) DMT. Relapse rate after switch to platform injectable, oral or infusion DMT was modeled with negative binomial regression, adjusted for pre-identified confounders (age at onset, disease duration, sex, race/ethnicity, body mass index, first event severity and localization, baseline annualized relapse rate (ARR), MRI new T2 lesions, MRI gadolinium-enhancing lesions, EDSS).
Result(s): 212 children switched DMT before 18 years (67% female, 95% MS). Of these, 93 switched from injectable to injectable, 76 injectable to oral and 43 injectable to infusion. Compared to switching to another injectable, switchers to oral or infusion were older at onset (injectable 12.3 years vs oral 13.5, infusion 14.2) and switch date (injectable 14.6 years vs oral 16, infusion 15.7), and switchers to infusion were more likely to have new enhancing lesions prior to switch (injectable 45% vs oral 28%, infusion 67%). Other baseline characteristics were not significantly different between groups. In adjusted analysis, compared to switchers from injectable to injectable (ARR 0.59, 95%CI 0.28-1.26), relapse rates were lower for switchers from injectable to oral (ARR 0.22, 95%CI 0.10-0.48; rate ratio 0.38, 95%CI 0.21-0.69) and injectable to infusion (ARR 0.15, 95%CI 0.06-0.35; rate ratio 0.25, 95%CI 0.11-0.53) (p < 0.001). The adjusted number needed to treat to prevent 1 relapse with oral over injectable was 2.70 and infusion over injectable was 2.22.
Conclusion(s): Switching from platform injectable to oral or infusion as opposed to another injectable DMT led to better disease activity control of pediatric MS. Long-term safety data for oral and infusion DMTs are required

OBJECTIVE/UNASSIGNED:Cognitive involvement in pediatric multiple sclerosis (MS) relative to adult MS is less defined. This study advances our understanding by measuring cognitive performances in pediatric MS, adult MS, and pediatric healthy controls. METHODS/UNASSIGNED:Consecutive relapsing pediatric MS participants from the United States Network of Pediatric MS Centers were compared with pediatric healthy controls and adults with relapsing MS. Participants were compared on two screening batteries: the Brief International Cognitive Assessment for MS and the Cogstate Brief Battery. Results were transformed to age-normative z scores. RESULTS/UNASSIGNED: < 0.001). CONCLUSION/UNASSIGNED:Pediatric MS patients do not differ from healthy pediatric controls on cognitive screens but perform better than adults with MS.