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Neuropsychological test performance of former American football players

Alosco, Michael L; Barr, William B; Banks, Sarah J; Wethe, Jennifer V; Miller, Justin B; Pulukuri, Surya Vamsi; Culhane, Julia; Tripodis, Yorghos; Adler, Charles H; Balcer, Laura J; Bernick, Charles; Mariani, Megan L; Cantu, Robert C; Dodick, David W; McClean, Michael D; Au, Rhoda; Mez, Jesse; Turner, Robert W; Palmisano, Joseph N; Martin, Brett; Hartlage, Kaitlin; Cummings, Jeffrey L; Reiman, Eric M; Shenton, Martha E; Stern, Robert A
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.
PMCID:9808953
PMID: 36597138
ISSN: 1758-9193
CID: 5409932

Hand Dexterity Improves in Patients with Progressive Multiple Sclerosis (MS) with Telerehabilitation Using Transcranial Direct Current Stimulation (tDCS) [Meeting Abstract]

Charvet, L; Pilloni, G; Lustberg, M; Malik, M; Feinberg, C; Gutman, J; Krupp, L; Raghavan, P
Abstract Background: Loss of hand dexterity is disabling and reduces quality of life. People living with progressive forms of MS have marked neurologic disabilities but limited rehabilitation options. Transcranial direct current stimulation (tDCS) is a method of noninvasive brain stimulation in which stimulation delivered during motor training can strengthen outcomes. We have established a remotely supervised tDCS (RS-tDCS) protocol that delivers multiple stimulation sessions paired with training to participants at home.
Objective(s): To evaluate a blinded randomized sham-controlled clinical trial of active vs. sham tDCS paired with manual dexterity training for people with progressive MS.
Method(s): We recruited right-hand dominant individuals with progressive MS and hand dexterity impairment. Participants completed 20 sessions of daily (M-F) manual dexterity and were randomized to either active (2.0 mA) or sham primary motor cortex (M1-SO) tDCS. Manual dexterity was measured with the Nine-Hole Peg Test (9HPT) and Dellon-Modified Moberg Pick-Up test (MMPUT) at baseline and study end and transformed to normative z-scores for comparison.
Result(s): Participants were n=60 with primary (32%) or secondary (68%) progressive MS (52% female, ages 37-72 years, and a median Expanded Disability Status Scale (EDSS) score of 5.0 [1.5-7.5]). The intervention was safe and well tolerated, with n=59/60 (98%) completing 18/20 daily sessions. Combining hands and tasks, the full group improved following the manual dexterity training (mean z-score improvement 1.64+/-9.53, p=0.016). Active tDCS led to greater improvement (mean z-score improvement 4.51+/-8.78, p=0.001). Analyzing those with right- or left-hand impairment at baseline, the active tDCS group had significant improvement on the 9HPT (Right: p=0.036, Left: p=0.028) and trended towards significant improvement for the MMPUT (Right: p=0.071, Left: p=0.079).
Conclusion(s): At-home manual dexterity training paired with tDCS is a safe, tolerable, and feasible intervention for people with progressive MS and hand impairment. Training outcomes are augmented with simultaneous M1-SO tDCS. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: tDCS, motor training, multiple sclerosis, teleintervention
Copyright
EMBASE:2022769993
ISSN: 1876-4754
CID: 5511542

Remotely Supervised tDCS for Persistent Post-Traumatic Headache in Veterans (ReStore) [Meeting Abstract]

Androulakis, M; Mangold, K; Harrison, A; Moore, R D; Guo, S; Zhang, J; Datta, A; Bikson, M; Charvet, L
Abstract Objectives: Evaluate feasibility and preliminary efficacy of remotely supervised transcranial Direct Current Stimulation (RS-tDCS) interventions for persistent post-traumatic headache (PPTH) secondary to mild TBI (mTBI).
Method(s): Veterans with PPTH completed a 28-day baseline observation of headache days and received either active or sham RS-tDCS paired with mindfulness meditation. This 4-week intervention of 20-minutes daily (M-F) RS-tDCS (anodal stimulation dlPFC) was monitored via VA Video Connect. Feasibility was determined by the number of participants completing >=80% of the intervention. Efficacy was measured by changes in number of moderate/severe headache days from baseline period to the end of treatment phase, and 4-week post-treatment follow-up. Secondary endpoints included total number of headache days, acute pain medication use, as well as headache- and mTBI-related disability.
Result(s): Twenty-six veterans (46.6+/-8.7 years) with PPTH completed baseline observations and were randomized to either active (n=13) or sham (n=13) treatment groups. A total of 22/25 (88%) participants fully completed either active (10/12) or sham (12/13) interventions (p=.0.59). Within-group analyses reveled significant reductions in moderate/severe headache days in the active (p=0.04) but not sham (p=0.54) groups. This resulted in a trend towards significant reductions in moderate/severe headache days in the active vs. sham groups (p = 0.07). Active participants also demonstrated a reduction in total number of headache days during treatment (p=0.04) where the sham group did not (p=0.70). There is statistically significant reduction in total number of headache days during treatment for active vs. sham participants (p=0.03). No significant differences were maintained during the 4-week post-treatment follow-up (p's>0.05).
Conclusion(s): RS-tDCS treatment feasible with high adherence and effective for veterans with PPTH. Findings suggest that active RS-tDCS via dlPFC reduce headache frequency and improve clinical outcomes. A larger phase II study is warranted to confirm these findings and inform evaluation for clinical use. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: tDCS, Persistent Post-traumatic headache, Veterans, mTBI
Copyright
EMBASE:2022769609
ISSN: 1876-4754
CID: 5511552

Non-invasive brain stimulation for fatigue in post-acute sequelae of SARS-CoV-2 (PASC)

Santana, Kelly; França, Eduardo; Sato, João; Silva, Ana; Queiroz, Maria; de Farias, Julia; Rodrigues, Danniely; Souza, Iara; Ribeiro, Vanessa; Caparelli-Dáquer, Egas; Teixeira, Antonio L; Charvet, Leigh; Datta, Abhishek; Bikson, Marom; Andrade, Suellen
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.
PMCID:9867562
PMID: 36693536
ISSN: 1876-4754
CID: 5419562

Remotely supervised at-home tDCS for veterans with persistent post-traumatic headache: a double-blind, sham-controlled randomized pilot clinical trial

Charvet, Leigh; Harrison, Adam T; Mangold, Kiersten; Moore, Robert Davis; Guo, Siyuan; Zhang, Jiajia; Datta, Abhishek; Androulakis, X Michelle
BACKGROUND/UNASSIGNED:Currently, there are no FDA approved therapies for persistent post-traumatic headache (PPTH) secondary to traumatic brain injury (TBI). As such neither headache nor TBI specialists have an effective means to manage PPTH. Thus, the objective of the present pilot trial was to evaluate the feasibility and preliminary efficacy of a four-week at-home remotely supervised transcranial direct current stimulation (RS-tDCS) intervention for veterans with PPTH. METHODS/UNASSIGNED: = 13) RS-tDCS, with anodal stimulation over left dlPFC and cathodal over occipital pole. Following a four-week baseline, participants completed 20-sessions of active or sham RS-tDCS with real-time video monitoring over a period of four-weeks. Participants were assessed again at the end of the intervention and at four-weeks post-intervention. Primary outcomes were overall adherence rate (feasibility) and change in moderate-to-severe headache days per month (efficacy). Secondary outcomes were changes in total number of headache days, and PPTH-related functional outcomes. RESULTS/UNASSIGNED: = 0.03), compared to sham during-treatment (-4.0 ± 5.2 vs. 1.5 ± 3.8), and 4-week follow-up (-2.1 ± 7.2 vs. -0.2 ± 4.4). CONCLUSION/UNASSIGNED:The current results indicate our RS-tDCS paradigm provides a safe and effective means for reducing the severity and number of headache days in veterans with PPTH. High treatment adherence rate and the remote nature of our paradigm indicate RS-tDCS may be a feasible means to reduce PPTH, especially for veterans with limited access to medical facilities.Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT04012853].
PMCID:10196360
PMID: 37213913
ISSN: 1664-2295
CID: 5543622

Home-administered transcranial direct current stimulation is a feasible intervention for depression: an observational cohort study

Charvet, Leigh; George, Allan; Charlson, Erik; Lustberg, Matthew; Vogel-Eyny, Amy; Eilam-Stock, Tehila; Cho, Hyein; Best, Pamela; Fernandez, Luis; Datta, Abhishek; Bikson, Marom; Nazim, Kamran; Pilloni, Giuseppina
Transcranial direct current stimulation (tDCS) is an emerging treatment for major depression. We recruited participants with moderate-to-severe major depressive episodes for an observational clinical trial using Soterix Medical's tDCS telehealth platform as a standard of care. The acute intervention consisted of 28 sessions (5 sessions/week, 6 weeks) of the left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA × 30 min) followed by a tapering phase of weekly sessions for 4 weeks (weeks 7-10). The n = 16 completing participants had a significant reduction in depressive symptoms by week 2 of treatment [Montgomery-Åsberg Depression Rating Scale (MADRS), Baseline: 28.00 ± 4.35 vs. Week 2: 17.12 ± 5.32, p < 0.001] with continual improvement across each biweekly timepoint. Acute intervention responder and remission rates were 75 and 63% and 88 and 81% following the taper period (week 10).
PMCID:10477781
PMID: 37674552
ISSN: 1664-0640
CID: 5602552

Digitalized transcranial electrical stimulation: A consensus statement

Brunoni, Andre R; Ekhtiari, Hamed; Antal, Andrea; Auvichayapat, Paradee; Baeken, Chris; Benseñor, Isabela M; Bikson, Marom; Boggio, Paulo; Borroni, Barbara; Brighina, Filippo; Brunelin, Erome; Carvalho, Sandra; Caumo, Wolnei; Ciechanski, Patrick; Charvet, Leigh; Clark, Vincent P; Cohen Kadosh, Roi; Cotelli, Maria; Datta, Abhishek; Deng, Zhi-De; De Raedt, Rudi; De Ridder, Dirk; Fitzgerald, Paul B; Floel, Agnes; Frohlich, Flavio; George, Mark S; Ghobadi-Azbari, Peyman; Goerigk, Stephan; Hamilton, Roy H; Jaberzadeh, Shapour J; Hoy, Kate; Kidgell, Dawson J; Zonoozi, Arash Khojasteh; Kirton, Adam; Laureys, Steven; Lavidor, Michal; Lee, Kiwon; Leite, Jorge; Lisanby, Sarah H; Loo, Colleen; Martin, Donel M; Miniussi, Carlo; Mondino, Marine; Monte-Silva, Katia; Morales-Quezada, Leon; Nitsche, Michael A; Okano, Alexandre H; Oliveira, Claudia S; Onarheim, Balder; Pacheco-Barrios, Kevin; Padberg, Frank; Nakamura-Palacios, Ester M; Palm, Ulrich; Paulus, Walter; Plewnia, Christian; Priori, Alberto; Rajji, Tarek K; Razza, Lais B; Rehn, Erik M; Ruffini, Giulio; Schellhorn, Klaus; Zare-Bidoky, Mehran; Simis, Marcel; Skorupinski, Pawel; Suen, Paulo; Thibaut, Aurore; Valiengo, Leandro C L; Vanderhasselt, Marie-Anne; Vanneste, Sven; Venkatasubramanian, Ganesan; Violante, Ines R; Wexler, Anna; Woods, Adam J; Fregni, Felipe
OBJECTIVE:Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES. METHODS:We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. RESULTS:The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity. CONCLUSIONS:Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. SIGNIFICANCE/CONCLUSIONS:We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.
PMID: 36115809
ISSN: 1872-8952
CID: 5336632

Combination of transcranial direct current stimulation with online cognitive training improves symptoms of Post-acute Sequelae of COVID-19: A case series [Letter]

Cavendish, Beatriz A; Lima, Alisson; Bertola, Laiss; Charvet, Leigh; Bikson, Marom; Brunoni, Andre R; Vidal, Kallene S
PMCID:9528061
PMID: 36202328
ISSN: 1876-4754
CID: 5351672

A new look at cognitive functioning in pediatric MS

Krupp, Lauren B; Waubant, Emmanuelle; Waltz, Michael; Casper, T Charles; Belman, Anita; Wheeler, Yolanda; Ness, Jayne; Graves, Jennifer; Gorman, Mark; Benson, Leslie; Mar, Soe; Goyal, Manu; Schreiner, Teri; Weinstock-Guttman, Bianca; Rodriguez, Moses; Tillema, Jan-Mendelt; Lotze, Timothy; Aaen, Greg; Rensel, Mary; Rose, John; Chitinis, Tanuja; George, Allan; Charvet, Leigh E
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.
PMID: 36189711
ISSN: 1477-0970
CID: 5351332

Real-world effectiveness of switching treatment after initial platform injectable disease-modifying therapies in pediatric multiple sclerosis in the US [Meeting Abstract]

Abrams, A; Waltz, M; Casper, T C; Aaen, G; Benson, L; Charvet, L; Chitnis, T; Francisco, C; Gorman, M; Goyal, M; Graves, J; Krupp, L; Lotze, T; Mar, S; Rensel, M; Rodriguez, M; Rose, J; Rutatangwa, A; Schreiner, T; Shukla, N; Weinstock-Guttman, B; Wheeler, Y; Waubant, E; Krysko, K
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
EMBASE:639568224
ISSN: 1477-0970
CID: 5377902