Digitalized transcranial electrical stimulation: A consensus statement
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.
Combination of transcranial direct current stimulation with online cognitive training improves symptoms of Post-acute Sequelae of COVID-19: A case series [Letter]
A new look at cognitive functioning in pediatric MS
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:â€‰<â€‰0.001). CONCLUSION/UNASSIGNED:Pediatric MS patients do not differ from healthy pediatric controls on cognitive screens but perform better than adults with MS.
Cerebral metabolic rate of oxygen (CMRO2) changes measured with simultaneous tDCS-MRI in healthy adults
BACKGROUND:Transcranial direct current stimulation (tDCS) is a safe and well-tolerated noninvasive technique used for cortical excitability modulation. tDCS has been extensively investigated for its clinical applications; however further understanding of its underlying in-vivo physiological mechanisms remains a fundamental focus of current research. OBJECTIVES/OBJECTIVE:) using simultaneous MRI in healthy adults to provide a reference frame for its neurobiological mechanisms. METHODS:at three time points: pre-, during- and post- 15Â minutes of 2.0Â mA tDCS on left anodal dorsolateral prefrontal cortex. RESULTS:significantly increased by 5.9Â % during-tDCS (175.68Â Â±Â 30.78Â Âµmol/100g/min) compared to pre-tDCS (165.84Â Â±Â 25.32Â Âµmol/100g/min; pÂ =Â 0.0015), maintaining increased levels in post-tDCS (176.86Â Â±Â 28.58Â Âµmol/100g/min). CONCLUSIONS:changes due to tDCS in healthy adults that may be incorporated in clinical studies to evaluate its therapeutic potential.
Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use
Transcranial direct current stimulation (tDCS) is a safe and well-tolerated noninvasive method for stimulating the brain that is rapidly developing into a treatment method for various neurological and psychiatric conditions. In particular, there is growing evidence of a therapeutic role for tDCS in ameliorating or delaying the cognitive decline in Alzheimer's disease (AD). We provide a brief overview of the current development and application status of tDCS as a nonpharmacological therapeutic method for AD and mild cognitive impairment (MCI), summarize the levels of evidence, and identify the improvements needed for clinical applications. We also suggest future directions for large-scale controlled clinical trials of tDCS in AD and MCI, and emphasize the necessity of identifying the mechanistic targets to facilitate clinical applications.
Tolerability and feasibility of at-home remotely supervised transcranial direct current stimulation (RS-tDCS): Single-center evidence from 6,779 sessions
INTRODUCTION/BACKGROUND:The ability to deploy transcranial direct current stimulation (tDCS) at home is a key usability advantage to support scaling for pivotal clinical trials. We have established a home-based tDCS protocol for use in clinical trials termed remotely supervised (RS)-tDCS. OBJECTIVE:To report the tolerability and feasibility of tDCS sessions completed to date using RS-tDCS in clinical trials. METHODS:We analyzed tolerability (i.e., adverse events, AEs) reported in six Class I/II/III trials using RS-tDCS to study symptom outcomes over 10 to 60 daily applications. Across the six clinical trials, 308 participants (18-78 years old) completed an average of 23 sessions for a total of 6779 RS-tDCS administrations. The majority of participants were diagnosed with multiple sclerosis, and open-label trials included those diagnosed with a range of other conditions (e.g., Parkinson's disease, post-stroke aphasia, traumatic brain injury, cerebellar ataxia), with minimum-to-severe neurologic disability. Clinical trial feasibility (i.e., treatment fidelity and blinding integrity) was examined using two Class I randomized controlled trials (RCTs). RESULTS:No serious AEs occurred. Across administrations, three sessions (0.04%) were aborted due to discomfort, but no participant discontinued due to tolerability. The AEs most commonly reported by participants were tingling (68%), itching (41%) and warmth sensation (42%) at the electrode site, and these were equally reported in active and sham tDCS conditions. The two Class I RCTs resulted in rapid enrollment, high fidelity to treatment completion, and blinding integrity. CONCLUSIONS:At-home RS-tDCS is tolerable, including when used over extended periods of time. Home-based RS-tDCS is feasible and can enable Class I tDCS clinical trial designs.
Risk of COVID-19 infection and severe disease in MS patients on different disease-modifying therapies
BACKGROUND:The risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating increased risks of infection with B-cell-depleting (anti-CD20) therapies and severity, while others fail to observe an association. Most existing studies are limited by a reliance on 'numerator' data (i.e., COVID-19 cases) only. OBJECTIVE:To assess the risks of COVID-19 by DMT, this study aimed to assess both 'numerator' (patients with SARS-CoV-2 infection) and 'denominator' data (all patients treated with DMTs of interest) to determine if any DMTs impart an increased risk of SARS-CoV-2 infection or disease severity. METHODS:We systematically reviewed charts and queried patients during clinic encounters in the NYU MS Comprehensive Care Center (MSCCC) for evidence of COVID-19 in all patients who were on the most commonly used DMTs in our clinic (sphingosine-1-phosphate receptor (S1P) modulators (fingolimod/siponimod), rituximab, ocrelizumab, fumarates (dimethyl fumarate/diroximel fumarate), and natalizumab). COVID-19 status was determined by clinical symptoms (CDC case definition) and laboratory testing where available (SARS-CoV-2 PCR, SARS-CoV-2 IgG). Multivariable analyses were conducted to determine predictors of infection and severe disease (hospitalization or death) using SARS-CoV-2 infected individuals per DMT group and all individuals on a given DMT as denominator. RESULTS:We identified 1,439 MS patients on DMTs of interest, of which 230 had lab-confirmed (nâ€¯=â€¯173; 75.2%) or suspected (nâ€¯=â€¯57; 24.8%) COVID-19. Infection was most frequent in those on rituximab (35/138; 25.4%), followed by fumarates (39/217; 18.0%), S1P modulators (43/250; 17.2%), natalizumab (36/245; 14.7%), and ocrelizumab (77/589; 13.1%). There were 14 hospitalizations and 2 deaths. No DMT was found to be significantly associated with increased risk of SARS-CoV-2 infection. Rituximab was a predictor of severe SARS-CoV-2 infection among patients with SARS-CoV-2 infection (OR 6.7; 95% CI 1.1-41.7) but did not reach statistical significance when the entire patient population on DMT was used (OR 2.8; 95% CI 0.6-12.2). No other DMT was associated with an increased risk of severe COVID-19. CONCLUSIONS:Analysis of COVID-19 risk among all patients on the commonly used DMTs did not demonstrate increased risk of infection with any DMT. Rituximab was associated with increased risk for severe disease.
Factors supporting availability of home-based Neuromodulation using remote supervision in middle-income countries; Brazil experience [Letter]
A novel disease specific scale to characterize the symptoms and impacts of fatigue in US adults with relapsing multiple sclerosis: A real-world study
BACKGROUND:Fatigue is among the most frequent and disabling symptoms in patients with relapsing multiple sclerosis (RMS). OBJECTIVE:To measure MS fatigue and its impact on daily life in a real-world US population using an MS-specific patient-reported outcome (PRO) instrument, the Fatigue Symptoms and Impacts Questionnaire-RMS (FSIQ-RMS). METHODS:This ongoing prospective study recruited RMS patients from an online patient community (Carenity) across US. Baseline assessment data are reported. Participants completed questionnaires, including the 20-item FSIQ-RMS questionnaire, with the first seven symptom-related items collected daily for seven days, and the other 13 items on the seventh day assessing impacts of fatigue. The FSIQ-RMS scores range from 0 to 100 (higher score=greater severity). The impact of fatigue on several aspects of patients' lives was rated from 0 (no impact) to 10 (very high impact). Data on disease history, disease status, sleep, social and emotional functioning were also captured. Baseline assessment data of 300 RMS patients are reported while follow-up assessments up to 18 months are planned. RESULTS:300 RMS participants completed the 7-day assessment (mean age 43.0 years, 88% women). Fatigue was rated as severe, with a mean score of 57.3 for the FSIQ-RMS symptom domain; 3 impact sub-domain scores were 42.3, 43.4 and 50.1 (physical, cognitive/emotional, and coping). Participants who were not in relapse (78%) reported less severe fatigue than those in relapse (22%): meanÂ±SD symptom score of 54.6Â Â±Â 17.8 vs. 67.0Â Â±Â 19.7, p<Â 0.001. Fatigue had a higher intensity among those with depression than without (49% vs. 51%, with mean Â± SD symptom score of 62.8Â Â±Â 16.9 vs. 52.1Â Â±Â 19.3, p<Â 0.001), and among those with sleep disorder than without (27% vs. 73%, 61.2Â Â±Â 19.2 vs. 55.9Â Â±Â 18.6; p<Â 0.05). The most common factor associated with increased fatigue was heat exposure (82%). Most participants (52%) reported experiencing fatigue before their MS diagnosis. CONCLUSION/CONCLUSIONS:Fatigue influences daily functioning for most patients with RMS. The FSIQ-RMS is a novel and MS-specific PRO measure that can advance the understanding and management of fatigue.
Demographic and social determinants of cognitive dysfunction following hospitalization for COVID-19
BACKGROUND:Persistent cognitive symptoms have been reported following COVID-19 hospitalization. We investigated the relationship between demographics, social determinants of health (SDOH) and cognitive outcomes 6-months after hospitalization for COVID-19. METHODS:We analyzed 6-month follow-up data collected from a multi-center, prospective study of hospitalized COVID-19 patients. Demographic and SDOH variables (age, race/ethnicity, education, employment, health insurance status, median income, primary language, living arrangements, and pre-COVID disability) were compared between patients with normal versus abnormal telephone Montreal Cognitive Assessments (t-MOCA; scores<18/22). Multivariable logistic regression models were constructed to evaluate predictors of t-MoCA. RESULTS:Of 382 patients available for 6-month follow-up, 215 (56%) completed the t-MoCA (nÂ =Â 109/215 [51%] had normal and nÂ =Â 106/215 [49%] abnormal results). 14/215 (7%) patients had a prior history of dementia/cognitive impairment. Significant univariate predictors of abnormal t-MoCA included older age, â‰¤12Â years of education, unemployment pre-COVID, Black race, and a pre-COVID history of cognitive impairment (all pÂ <Â 0.05). In multivariable analyses, education â‰¤12Â years (adjusted OR 5.21, 95%CI 2.25-12.09), Black race (aOR 5.54, 95%CI 2.25-13.66), and the interaction of baseline functional status and unemployment prior to hospitalization (aOR 3.98, 95%CI 1.23-12.92) were significantly associated with abnormal t-MoCA scores after adjusting for age, history of dementia, language, neurological complications, income and discharge disposition. CONCLUSIONS:Fewer years of education, Black race and unemployment with baseline disability were associated with abnormal t-MoCA scores 6-months post-hospitalization for COVID-19. These associations may be due to undiagnosed baseline cognitive dysfunction, implicit biases of the t-MoCA, other unmeasured SDOH or biological effects of SARS-CoV-2.