This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3–13 A/m2) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 mA, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1,000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations.

Purpose:To promote understanding of cognitive impairment in multiple sclerosis (MS), recommend optimal screening, monitoring, and treatment strategies, and address barriers to optimal management.Methods:The National MS Society (“Society”) convened experts in cognitive dysfunction (clinicians, researchers, and lay people with MS) to review the published literature, reach consensus on optimal strategies for screening, monitoring, and treating cognitive changes, and propose strategies to address barriers to optimal care.Recommendations:Based on current evidence, the Society makes the following recommendations, endorsed by the Consortium of Multiple Sclerosis Centers and the International Multiple Sclerosis Cognition Society:Increased professional and patient awareness/education about the prevalence, impact, and appropriate management of cognitive symptoms.For adults and children (8+ years of age) with clinical or magnetic resonance imaging (MRI) evidence of neurologic damage consistent with MS:As a minimum, early baseline screening with the Symbol Digit Modalities Test (SDMT) or similarly validated test, when the patient is clinically stable;Annual re-assessment with the same instrument, or more often as needed to (1) detect acute disease activity; (2) assess for treatment effects (e.g. starting/changing a disease-modifying therapy) or for relapse recovery; (3) evaluate progression of cognitive impairment; and/or (4) screen for new-onset cognitive problems.For adults (18+ years): more comprehensive assessment for anyone who tests positive on initial cognitive screening or demonstrates significant cognitive decline, especially if there are concerns about comorbidities or the individual is applying for disability due to cognitive impairment.For children (<18 years): neuropsychological evaluation for any unexplained change in school functioning (academic or behavioral).Remedial interventions/accommodations for adults and children to improve functioning at home, work, or school.

Background Fatigue is a common and debilitating feature of multiple sclerosis (MS) that remains without reliably effective treatment. Transcranial direct current stimulation (tDCS) is a promising option for fatigue reduction. We developed a telerehabilitation protocol that delivers tDCS to participants at home using specially designed equipment and real-time supervision (remotely supervised transcranial direct current stimulation (RS-tDCS)). Objective To evaluate whether tDCS can reduce fatigue in individuals with MS. Methods Dorsolateral prefrontal cortex left anodal tDCS was administered using a RS-tDCS protocol, paired with 20 minutes of cognitive training. Here, two studies are considered. Study 1 delivered 10 open-label tDCS treatments (1.5 mA; n = 15) compared to a cognitive training only condition (n = 20). Study 2 was a randomized trial of active (2.0 mA, n = 15) or sham (n = 12) delivered for 20 sessions. Fatigue was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS)—Fatigue Short Form. Results and conclusion In Study 1, there was modest fatigue reduction in the active group (−2.5 ± 7.4 vs −0.2 ± 5.3, p = 0.30, Cohen’s d = −0.35). However, in Study 2 there was statistically significant reduction for the active group (−5.6 ± 8.9 vs 0.9 ± 1.9, p = 0.02, Cohen’s d = −0.71). tDCS is a potential treatment for MS-related fatigue.

In the largest sample studied to date, we measured cognitive functioning in children and adolescents with pediatric multiple sclerosis (n =187) as well as those with clinically isolated syndrome (n =44). Participants were consecutively enrolled from six United States PediatricMultiple Sclerosis Centers of Excellence. Participants had amean of 14.8 ± 2.6 years of age and an average disease duration of 1.9 ± 2.2 years. A total of 65 (35%) children with multiple sclerosis and 8 (18%) with clinically isolated syndrome met criteria for cognitive impairment. The most frequent areas involved were fine motor coordination (54%), visuomotor integration (50%), and speeded information processing (35%). A diagnosis of multiple sclerosis (odds ratio = 3.60, confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability (odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only independent predictors of cognitive impairment. Cognitive impairment may occur early in these patients, and prompt recognition is critical for their care.

BackgroundNeuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities.ObjectiveThis report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment.MethodsThe National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs.ResultsAdvances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them.ConclusionsThese recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders.