Remotely monitored transcranial direct current stimulation in pediatric cerebral palsy: open label trial protocol.

BACKGROUND: Pediatric applications of non-invasive brain stimulation using transcranial direct current stimulation (tDCS) have demonstrated its safety with few adverse events reported. Remotely monitored tDCS, as an adjuvant intervention to rehabilitation, may improve quality of life for children with cerebral palsy (CP) through motor function improvements, reduced treatment costs, and increased access to tDCS therapies. Our group previously evaluated the feasibility of a remotely monitored mock tDCS setup in which families and children successfully demonstrated the ability to follow tDCS instructional guidance. METHODS AND DESIGN: Here, we designed a protocol to investigate the feasibility, safety, and tolerability of at-home active transcranial direct current stimulation in children with CP with synchronous supervision from laboratory investigators. Ten participants will be recruited to participate in the study for 5 consecutive days with the following sessions: tDCS setup practice on day 1, sham tDCS on day 2, and active tDCS on days 3-5. Sham stimulation will consist of an initial 30-second ramp up to 1.5 mA stimulation followed by a 30-second ramp down. Active stimulation will be delivered at 1.0 - 1.5 mA for 20 minutes and adjusted based on child tolerance. Feasibility will be evaluated via photographs of montage setup and the quality of stimulation delivery. Safety and tolerability will be assessed through an adverse events survey, the Box and Blocks Test (BBT) motor assessment, and a setup ease/comfort survey. DISCUSSION: We expect synchronous supervision of at-home teleneuromodulation to be tolerable and safe with increasing stimulation quality over repeated sessions when following a tDCS setup previously determined to be feasible. The findings will provide opportunity for larger clinical trials exploring efficacy and illuminate the potential of remotely monitored tDCS in combination with rehabilitation interventions as a means of pediatric neurorehabilitation. This will demonstrate the value of greater accessibility of non-invasive brain stimulation interventions and ultimately offer the potential to improve care and quality of life for children and families with CP. TRIAL REGISTRATION: October 8, 2021( https://clinicaltrials.gov/ct2/show/NCT05071586 ).

Study Protocol: Multimodal Longitudinal Assessment of Infant Brain Organization and Recovery in Perinatal Brain Injury.

PURPOSE: Perinatal brain injury is a primary cause of cerebral palsy, a condition resulting in lifelong motor impairment. Infancy is an important period of motor system development, including development of the corticospinal tract (CST), the primary pathway for cortical movement control. The interaction between perinatal stroke recovery, CST organization, and resultant motor outcome in infants is not well understood. METHODS: Here, we present a protocol for multimodal longitudinal assessment of brain development and motor function following perinatal brain injury using transcranial magnetic stimulation and magnetic resonance imaging to noninvasively measure CST functional and structural integrity across multiple time points in infants 3 to 24 months of age. We will further assess the association between cortical excitability, integrity, and motor function. DISCUSSION: This protocol will identify bioindicators of motor outcome and neuroplasticity and subsequently inform early detection, diagnosis, and intervention strategies for infants with perinatal stroke, brain bleeds, and related diagnoses.

Cardiovascular Effects of Transcranial Direct Current Stimulation and Bimanual Training in Children With Cerebral Palsy.

PURPOSE: To determine the influence of combined transcranial direct current stimulation (tDCS) to the motor cortex (M1) and bimanual training on cardiovascular function in children with cerebral palsy (CP). METHODS: Mean arterial pressure (MAP), heart rate (HR), and HR variability (HRV) were measured immediately before and after 20 minutes of cathodal tDCS to contralesional M1 and bimanual training on days 1, 6, and 10 of a 10-day trial in 8 participants (5 females, 7-19 years). RESULTS: Baseline MAP and HR were similar across days (93 ± 10 mm Hg and 90 ± 10 bpm, P > .05). MAP was similar from baseline to postintervention across all 3 days. Systolic pressure, diastolic pressure, nor HR significantly changed. HRV was not influenced by the 10-day intervention. CONCLUSIONS: Combined cathodal tDCS to M1 and bimanual training does not influence autonomic and cardiovascular function in children with CP due to perinatal stroke.

Neurite orientation dispersion and density imaging quantifies corticospinal tract microstructural organization in children with unilateral cerebral palsy.

Children with unilateral cerebral palsy (UCP) due to early brain injury exhibit disrupted connectivity of corticospinal tracts (CSTs), which can be quantified using diffusion-weighted magnetic resonance imaging (DWI). Diffusion tensor imaging (DTI) is commonly used to quantify white matter organization, however, this model lacks the biological specificity to accurately describe underlying microstructural properties. Newer approaches, such as neurite orientation dispersion and density imaging (NODDI), may provide more biologically accurate information regarding CST microstructure. In this study, we directly compared metrics of CST microstructure using NODDI and DTI models to characterize the microstructural organization of corticospinal pathways. Twenty participants with UCP participating in a neuromodulation/rehabilitation intervention underwent imaging including multi-shell DWI; 10 participants' datasets were adequately completed for neuroimaging analysis. Task fMRI-guided probabilistic tractography from motor cortex to brainstem was performed at baseline and follow-up to reconstruct the CSTs. Diffusion metrics were compared between hemispheres at baseline, and between baseline and follow-up to test for intervention effects. Correlation analyses were used to compare baseline metrics to changes in hand function following the intervention. DTI results showed that mean fractional anisotropy in lesioned and nonlesioned CSTs did not significantly differ, but mean, axial, and radial diffusivity were greater in the lesioned CST. For NODDI, intracellular volume fraction (ICVF) and orientation dispersion index (ODI) were lower in the lesioned CST. Unimanual function was strongly correlated with ICVF, but not FA. NODDI may reveal distinct properties of CST microstructure that are linked to motor function, indicating their potential in characterizing brain structure and development.

Transcranial Direct Current Stimulation (tDCS) Paired with Occupation-Centered Bimanual Training in Children with Unilateral Cerebral Palsy: A Preliminary Study.

Objective: We investigated the preliminary efficacy of cathodal transcranial direct current stimulation (tDCS) combined with bimanual training in children and young adults with unilateral cerebral palsy based on the principle of exaggerated interhemispheric inhibition (IHI). Methods: Eight participants with corticospinal tract (CST) connectivity from the lesioned hemisphere participated in an open-label study of 10 sessions of cathodal tDCS to the nonlesioned hemisphere (20 minutes) concurrently with bimanual, goal-directed training (120 minutes). We measured the frequency of adverse events and intervention efficacy with performance (bimanual-Assisting Hand Assessment (AHA)-and unimanual-Box and Blocks), self-report (Canadian Occupational Performance Measure (COPM), ABILHAND), and neurophysiologic (motor-evoked potential amplitude, cortical silent period (CSP) duration, and motor mapping) assessments. Results: All participants completed the study with no serious adverse events. Three of 8 participants showed gains on the AHA, and 4 of 8 participants showed gains in Box and Blocks (more affected hand). Nonlesioned CSP duration decreased in 6 of 6 participants with analyzable data. Cortical representation of the first dorsal interosseous expanded in the nonlesioned hemisphere in 4 of 6 participants and decreased in the lesioned hemisphere in 3 of 4 participants with analyzable data. Conclusions: While goal achievement was observed, objective measures of hand function showed inconsistent gains. Neurophysiologic data suggests nonlinear responses to cathodal stimulation of the nonlesioned hemisphere. Future studies examining the contributions of activity-dependent competition and cortical excitability imbalances are indicated.

Reference values of intrinsic muscle strength of the hand of adolescents and young adults.

STUDY DESIGN: A cross-sectional clinical measurement study. INTRODUCTION: Measuring intrinsic hand muscle strength helps evaluate hand function or therapeutic outcomes. However, there are no established normative values in adolescents and young adults between 13 and 20 years of age. PURPOSE OF THE STUDY: To measure hand intrinsic muscle strength and identify associated factors that may influence such in adolescents and young adults through use of the Rotterdam intrinsic hand myometer. METHODS: A total of 131 participants (male: 63; female: 68) between 13 and 20 years of age completed the strength measurements of abductor pollicis brevis, first dorsal interosseus (FDI), deep head of FDI and lumbrical of second digit, flexor pollicis brevis (FPB), and abductor digiti minimi. Two trials of the measurements of each muscle were averaged for analyses. Self-reported demographic data were used to examine the influences of age, sex, and body mass index (BMI) on intrinsic hand muscle strength. RESULTS: Normative values of intrinsic hand muscle strength were presented by age groups (13, 14, 15-16, 17-18, 19-20 year olds) for each sex category (male, female). A main effect of sex, but not age, on all the muscles on both the dominant (FPB: P = .02, others: P < .001) and non-dominant (FDI: P = .005, FPB: P = .01, others: P < .001) sides was found. A significant effect of BMI was found on dominant (P = .009) and non-dominant abductor pollicis brevis (P = .002). In addition, FDI (P = .005) and FPB (P = .002) were stronger on the dominant side than the non-dominant side. DISCUSSION: Intrinsic hand muscle strength may be influenced by different factors including sex, BMI, and hand dominance. A larger sample is needed to rigorously investigate the influence of age on intrinsic strength in male and female adolescents and young adults. CONCLUSION: The results provide reference values and suggest factors to be considered when evaluating hand function and therapeutic outcomes in both clinical and research settings. Further study is recommended. LEVEL OF EVIDENCE: VI.

Understanding Brain Reorganization in Infants With Perinatal Stroke Through Neuroexcitability and Neuroimaging.

PURPOSE: The primary aim of this proposed study is to evaluate brain reorganization patterns in infants with perinatal stroke between 3 and 5 months of age using transcranial magnetic stimulation and magnetic resonance imaging, with the addition of the General Movements Assessment. A secondary aim is to demonstrate feasibility and safety of infant-appropriate brain assessment protocols. METHODS: Ten infants with perinatal stroke will be enrolled. In this exploratory study, infants will first receive magnetic resonance imaging scanning during natural sleep to examine their corticospinal tract integrity. Infants will then receive transcranial magnetic stimulation to assess their corticomotor excitability. A General Movements Assessment video of at least 5 minutes will also be recorded. DISCUSSION: Study results will enhance our understanding of brain reorganization in infants with perinatal stroke. We expect these results will also guide the development of early interventions designed to mitigate maladaptive neuroplastic changes and improve long-term motor outcomes.

Case report of vasovagal syncope associated with single pulse transcranial magnetic stimulation in a healthy adult participant.

BACKGROUND: Non-invasive brain stimulation-related seizures or syncopal events are rare. However, we report on a syncopal event in a healthy female during a transcranial magnetic stimulation single-pulse testing session. CASE PRESENTATION: A 47-year-old healthy female presented for a transcranial magnetic stimulation session involving single-pulse assessment of cortical excitability. During the session, the participant appeared to have a brief event involving fainting and myoclonic jerks of the upper extremities. Orthostatic assessment was performed after the event and physician evaluation determined that this was a vasovagal syncopal event. The ethical aspects of this neurophysiology testing protocol were reviewed by the University of Minnesota Institutional Review Board (IRB), and formal IRB approval was deemed unnecessary for single-pulse assessment of healthy control participants not directly involved in a research study. Informed consent was obtained by the participant, including review of potential adverse events. CONCLUSION: Although rare and rarely reported, vasovagal syncopal events surrounding non-invasive brain stimulation do occur. Thorough pre-screening should incorporate assessment of history of syncope and a plan for risk mitigation if such an event should occur. A complete assessment of the impact of stimulation on the autonomic nervous system is unknown. As such studies expand into patients with myriad neurologic diagnoses, further studies on this effect, in both healthy control and patient populations, are warranted. Such knowledge could contribute to identification of the optimal study participant, and improvements in techniques of stimulation administration.

Focal hand dystonia: individualized intervention with repeated application of repetitive transcranial magnetic stimulation.

OBJECTIVES: To examine for individual factors that may predict response to inhibitory repetitive transcranial magnetic stimulation (rTMS) in focal hand dystonia (FHD); to present the method for determining optimal stimulation to increase inhibition in a given patient; and to examine individual responses to prolonged intervention. DESIGN: Single-subject design to determine optimal parameters to increase inhibition for a given subject and to use the selected parameters once per week for 6 weeks, with 1-week follow-up, to determine response. SETTING: Clinical research laboratory. PARTICIPANTS: A volunteer sample of subjects with FHD (N = 2). One participant had transcranial magnetic stimulation responses indicating impaired inhibition, and the other had responses within normative limits. INTERVENTIONS: There were 1200 pulses of 1-Hz rTMS delivered using 4 different stimulation sites/intensity combinations: primary motor cortex at 90% or 110% of resting motor threshold (RMT) and dorsal premotor cortex (PMd) at 90% or 110% of RMT. The parameters producing the greatest within-session increase in cortical silent period (CSP) duration were then used as the intervention. MAIN OUTCOME MEASURES: Response variables included handwriting pressure and velocity, subjective symptom rating, CSP, and short latency intracortical inhibition and facilitation. RESULTS: The individual with baseline transcranial magnetic stimulation responses indicating impaired inhibition responded favorably to the repeated intervention, with reduced handwriting force, an increase in the CSP, and subjective report of moderate symptom improvement at 1-week follow-up. The individual with normative baseline responses failed to respond to the intervention. In both subjects, 90% of RMT to the PMd produced the greatest lengthening of the CSP and was used as the intervention. CONCLUSIONS: An individualized understanding of neurophysiological measures can be an indicator of responsiveness to inhibitory rTMS in focal dystonia, with further work needed to determine likely responders versus nonresponders.

Safety of primed repetitive transcranial magnetic stimulation and modified constraint-induced movement therapy in a randomized controlled trial in pediatric hemiparesis.

OBJECTIVE: To investigate the safety of combining a 6-Hz primed low-frequency repetitive transcranial magnetic stimulation (rTMS) intervention in the contralesional hemisphere with a modified constraint-induced movement therapy (mCIMT) program in children with congenital hemiparesis. DESIGN: Phase 1 randomized, double-blinded, placebo-controlled pretest/posttest trial. SETTING: University academic facility and pediatric specialty hospital. PARTICIPANTS: Subjects (N = 19; age range, 8-17 y) with congenital hemiparesis caused by ischemic stroke or periventricular leukomalacia. No subject withdrew because of adverse events. All subjects included completed the study. INTERVENTIONS: Subjects were randomized to 1 of 2 groups: either real rTMS plus mCIMT (n = 10) or sham rTMS plus mCIMT (n = 9). MAIN OUTCOME MEASURES: Adverse events, physician assessment, ipsilateral hand function, stereognosis, cognitive function, subject report of symptoms assessment, and subject questionnaire. RESULTS: No major adverse events occurred. Minor adverse events were found in both groups. The most common events were headaches (real: 50%, sham: 89%; P = .14) and cast irritation (real: 30%, sham: 44%; P = .65). No differences between groups in secondary cognitive and unaffected hand motor measures were found. CONCLUSIONS: Primed rTMS can be used safely with mCIMT in congenital hemiparesis. We provide new information on the use of rTMS in combination with mCIMT in children. These findings could be useful in research and future clinical applications in advancing function in congenital hemiparesis.

Synergistic effect of combined transcranial direct current stimulation/constraint-induced movement therapy in children and young adults with hemiparesis: study protocol.

BACKGROUND: Perinatal stroke occurs in more than 1 in 2,500 live births and resultant congenital hemiparesis necessitates investigation into interventions which may improve long-term function and decreased burden of care beyond current therapies ( http://www.cdc.gov/ncbddd/cp/data.html ). Constraint-Induced Movement Therapy (CIMT) is recognized as an effective hemiparesis rehabilitation intervention. Transcranial direct current stimulation as an adjunct treatment to CIMT may potentiate neuroplastic responses and improve motor function. The methodology of a clinical trial in children designed as a placebo-controlled, serial -session, non-invasive brain stimulation trial incorporating CIMT is described here. The primary hypotheses are 1) that no serious adverse events will occur in children receiving non-invasive brain stimulation and 2) that children in the stimulation intervention group will show significant improvements in hand motor function compared to children in the placebo stimulation control group. METHODS/DESIGN: A randomized, controlled, double-blinded clinical trial. Twenty children and/or young adults (ages 8-21) with congenital hemiparesis, will be enrolled. The intervention group will receive ten 2-hour sessions of transcranial direct current stimulation combined with constraint-induced movement therapy and the control group will receive sham stimulation with CIMT. The primary outcome measure is safety assessment of transcranial direct current stimulation by physician evaluation, vital sign monitoring and symptom reports. Additionally, hand function will be evaluated using the Assisting Hand Assessment, grip strength and assessment of goals using the Canadian Occupational Performance Measure. Neuroimaging will confirm diagnoses, corticospinal tract integrity and cortical activation. Motor cortical excitability will also be examined using transcranial magnetic stimulation techniques. DISCUSSION: Combining non-invasive brain stimulation and CIMT interventions has the potential to improve motor function in children with congenital hemiparesis beyond each intervention independently. Such a combined intervention has the potential to benefit an individual throughout their lifetime. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02250092 Registered 18 September 2014.

Primed low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric hemiparesis: a randomized controlled trial.

AIM: The aim of this study was to determine the feasibility and efficacy of five treatments of 6 Hz primed, low-frequency, repetitive transcranial magnetic stimulation (rTMS) combined with constraint-induced movement therapy (CIMT) to promote recovery of the paretic hand in children with congenital hemiparesis. METHOD: Nineteen children with congenital hemiparesis aged between 8 and 17 years (10 males, nine females; mean age 10 years 10 months, SD 2 years 10 months; Manual Ability Classification Scale levels I-III) underwent five sessions of either real rTMS (n=10) or sham rTMS (n=9) alternated daily with CIMT. CIMT consisted of 13 days of continuous long-arm casting with five skin-check sessions. Each child received a total of 10 hours of one-to-one therapy. The primary outcome measure was the Assisting Hand Assessment (AHA) and the secondary outcome variables were the Canadian Occupational Performance Measure (COPM) and stereognosis. A Wilcoxon signed-rank sum test was used to analyze differences between pre- and post-test scores within the groups. Analysis of covariance was used to compute mean differences between groups adjusting for baseline. Fisher's exact test was used to compare individual change in AHA raw scores with the smallest detectable difference (SDD) of 4 points. RESULTS: All participants receiving treatment finished the study. Improvement in AHA differed significantly between groups (p=0.007). No significant differences in the secondary outcome measures were found. Eight out of 10 participants in the rTMS/CIMT group showed improvement greater than the SDD, but only two out of nine in the sham rTMS/CIMT group showed such improvement (p=0.023). No serious adverse events occurred. INTERPRETATION: Primed, low-frequency rTMS combined with CIMT appears to be safe, feasible, and efficacious in pediatric hemiparesis. Larger clinical trials are now indicated.

Single-pulse transcranial magnetic stimulation for assessment of motor development in infants with early brain injury.

INTRODUCTION: Single-pulse transcranial magnetic stimulation (TMS) has many applications for pediatric clinical populations, including infants with perinatal brain injury. As a noninvasive neuromodulation tool, single-pulse TMS has been used safely in infants and children to assess corticospinal integrity and circuitry patterns. TMS may have important applications in early detection of atypical motor development or cerebral palsy. AREAS COVERED: The authors identified and summarized relevant studies incorporating TMS in infants, including findings related to corticospinal development and circuitry, motor cortex localization and mapping, and safety. This special report also describes methodologies and safety considerations related to TMS assessment in infants, and discusses potential applications related to diagnosis of cerebral palsy and early intervention. EXPERT OPINION: Single-pulse TMS has demonstrated safety and feasibility in infants with perinatal brain injury and may provide insight into neuromotor development and potential cerebral palsy diagnosis. Additional research in larger sample sizes will more fully evaluate the utility of TMS biomarkers in early diagnosis and intervention. Methodological challenges to performing TMS in infants and technical/equipment limitations require additional consideration and innovation toward clinical implementation. Future research may explore use of noninvasive neuromodulation techniques as an intervention in younger children with perinatal brain injury to improve motor outcomes.

Single pulse transcranial magnetic stimulation (TMS) is a safe and noninvasive way to study brain activity in infants and children who have experienced brain injuries around the time of birth. Infants who have had an early brain injury may develop cerebral palsy, a developmental disability that affects movement. TMS uses a device that gives single pulses of energy to activate specific areas of the brain. This can be used to study how the brain connects to the muscles in the body through paths or 'tracts.' TMS helps researchers understand the development of the tracts and the potential need for therapy. This article reviews research studies that used TMS in infants and explains how TMS can be used to assess brain development. It also reviews safety considerations and challenges related to using TMS in infants. TMS could be a valuable tool for early diagnosis of cerebral palsy and could also help guide treatments for infants with brain injuries. However, more research is needed, using larger groups of infants, to potentially expand the use of TMS in clinical practice. Future directions include developing infant-specific research tools and using noninvasive brain stimulation to improve recovery for infants with brain injuries.

Anodal Contralesional tDCS Enhances CST Excitability Bilaterally in an Adolescent with Hemiparetic Cerebral Palsy: A Brief Report.

Hemiparetic cerebral palsy (HCP), weakness on one side of the body typically caused by perinatal stroke, is characterized by lifelong motor impairments related to alterations in the corticospinal tract (CST). CST reorganization could be a useful biomarker to guide applications of neuromodulatory interventions, such as transcranial direct current stimulation (tDCS), to improve the effectiveness of rehabilitation therapies. We evaluated an adolescent with HCP and CST reorganization who demonstrated persistent heightened CST excitability in both upper limbs following anodal contralesional tDCS. The results support further investigation of targeted tDCS as an adjuvant therapy to traditional neurorehabilitation for upper limb function.

Safety and feasibility of transcranial direct current stimulation stratified by corticospinal organization in children with hemiparesis.

Children with hemiparesis (CWH) due to stroke early in life face lifelong impairments in motor function. Transcranial direct current stimulation (tDCS) may be a safe and feasible adjuvant therapy to augment rehabilitation. Given the variability in outcomes following tDCS, tailored protocols of tDCS are required. We evaluated the safety, feasibility, and preliminary effects of a single session of targeted anodal tDCS based on individual corticospinal tract organization on corticospinal excitability. Fourteen CWH (age = 13.8 ± 3.63) were stratified into two corticospinal organization subgroups based on transcranial magnetic stimulation (TMS)-confirmed motor evoked potentials (MEP): ipsilesional MEP presence (MEPIL+) or absence (MEPIL-). Subgroups were randomized to real anodal or sham tDCS (1.5 mA, 20 min) applied to the ipsilesional (MEPIL + group) or contralesional (MEPIL- group) hemisphere combined with hand training. Safety was assessed with questionnaires and motor function evaluation, and corticospinal excitability was assessed at baseline and every 15 min for 1 h after tDCS. No serious adverse events occurred and anticipated minor side effects were reported and were self-limiting. Six of 14 participants had consistent ipsilesional MEPs (MEPIL + group). Paretic hand MEP amplitude increased in 5/8 participants who received real anodal tDCS to either the ipsilesional or contralesional hemisphere (+80% change). Application of tDCS based on individual corticospinal organization was safe and feasible with expected effects on excitability, indicating the potential for tailored tDCS protocols for CWH. Additional research involving expanded experimental designs is needed to confirm these effects and to determine if this approach can be translated into a clinically relevant intervention.

Global COVID-19 childhood disability data coordination: A collaborative initiative of the International Alliance of Academies of Childhood Disability.

PURPOSE: The International Alliance of Academies of Childhood Disability created a COVID-19 Task Force with the goal of understanding the global impact of COVID-19 on children with disabilities and their families. The aim of this paper is to synthesize existing evidence describing the impact of COVID-19 on people with disabilities, derived from surveys conducted across the globe. METHODS: A descriptive environmental scan of surveys was conducted. From June to November 2020, a global call for surveys addressing the impact of COVID-19 on disability was launched. To identify gaps and overlaps, the content of the surveys was compared to the Convention on the Rights of the Child and the International Classification of Functioning, Disability and Health. RESULTS: Forty-nine surveys, involving information from more than 17,230 participants around the world were collected. Overall, surveys identified that COVID-19 has negatively impacted several areas of functioning - including mental health, and human rights of people with disabilities and their families worldwide. CONCLUSION: Globally, the surveys highlight that impact of COVID-19 on mental health of people with disabilities, caregivers, and professionals continues to be a major issue. Rapid dissemination of collected information is essential for ameliorating the impact of COVID-19 across the globe.

Limited output transcranial electrical stimulation 2023 (LOTES-2023): Updates on engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk.

The objective and scope of this Limited Output Transcranial Electrical Stimulation 2023 (LOTES-2023) guidance is to update the previous LOTES-2017 guidance. These documents should therefore be considered together. The LOTES provides a clearly articulated and transparent framework for the design of devices providing limited output (specified low-intensity range) transcranial electrical stimulation for a variety of intended uses. These guidelines can inform trial design and regulatory decisions, but most directly inform manufacturer activities - and hence were presented in LOTES-2017 as "Voluntary industry standard for compliance controlled limited output tES devices". In LOTES-2023 we emphasize that these standards are largely aligned across international standards and national regulations (including those in USA, EU, and South Korea), and so might be better understood as "Industry standards for compliance controlled limited output tES devices". LOTES-2023 is therefore updated to reflect a consensus among emerging international standards, as well as best available scientific evidence. "Warnings" and "Precautions" are updated to align with current biomedical evidence and applications. LOTES standards applied to a constrained device dose range, but within this dose range and for different use-cases, manufacturers are responsible to conduct device-specific risk management.

Neuroplasticity: an appreciation from synapse to system.

OBJECTIVE: To integrate our functional knowledge in neurorehabilitation with a greater understanding of commonly held theories and current research in neuroplasticity. DESIGN: Literature review. SETTING: Not applicable. PARTICIPANTS: Animal and human research. INTERVENTIONS: Interventions specific to application in humans: constraint-induced movement therapy, transcranial magnetic stimulation, and transcranial direct current stimulation. MAIN OUTCOME MEASURES: Cortical excitability, blood oxygen level-dependent signal, and functional outcomes. RESULTS: There is increasing evidence elucidating the cellular and molecular mechanisms of plasticity of the nervous system including growth, modification, degradation, and even death of neurons. Some of these mechanisms directly correlate with therapy-induced behavioral changes, and all provide an understanding of the response of the nervous system to altered inputs. The understanding of neural correlates of behavior can then form the foundation for more productive, comprehensive interventions. CONCLUSIONS: The focus of recent research surrounds translational projects aimed at enhancing clinical outcomes. Knowledge of mechanisms underlying this adaptability is the foundation for our treatments, diagnoses, and prognoses. The increasing understanding of the mechanisms underlying neuroplasticity can guide, direct, and focus the practice of current and future therapies to greater efficacy and better functional outcomes in clinical rehabilitation.

Evaluating transcranial magnetic stimulation (TMS) induced electric fields in pediatric stroke.

Transcranial magnetic stimulation (TMS) is an increasingly popular tool for stroke rehabilitation. Consequently, researchers have started to explore the use of TMS in pediatric stroke. However, the application of TMS in a developing brain with pathologies comes with a unique set of challenges. The effect of TMS-induced electric fields has not been explored in children with stroke lesions. Here, we used finite element method (FEM) modeling to study how the electric field strength is affected by the presence of a lesion. We created individual realistic head models from MRIs (n = 6) of children with unilateral cerebral palsy due to perinatal stroke. We conducted TMS electric field simulations for coil locations over lesioned and non-lesioned hemispheres. We found that the presence of a lesion can strongly affect the electric field distribution. On the group level, the mean electric field strength did not differ between lesioned and non-lesioned hemispheres but exhibited a greater variability in the lesioned hemisphere. Other factors such as coil-to-cortex distance have a strong influence on the TMS electric field even in the presence of lesions. Our study has important implications for the delivery of TMS in children with brain lesions with respect to TMS dosing and coil placement.

Disrupted Access to Therapies and Impact on Well-Being During the COVID-19 Pandemic for Children With Motor Impairment and Their Caregivers.

OBJECTIVES: The aim of this study was to determine the impact of the COVID-19 pandemic on access to rehabilitation therapies and the impact of changes in therapy access on the physical and mental well-being of children with motor impairment and their caregivers. DESIGN: Caregivers of children younger than 18 yrs with childhood-onset motor impairment (primarily cerebral palsy) completed an anonymous survey through the online platform REDCap between May 5 and July 13, 2020. RESULTS: The survey was completed by 102 participants. Before the pandemic, 92 of 102 children (90%) were receiving one or more therapies; at the time surveyed, 55 children (54%) were receiving any therapies (P < 0.001). More than 40% of the sample reported increased child stress, decreased physical activity, and/or decline in mobility/movement. Participants who reported a decrease in number of therapies at the time surveyed more frequently reported lower satisfaction with treatment delivery (P < 0.001), a decline in child's mobility (P = 0.001), and increased caregiver stress (P = 0.004). Five qualitative themes were identified from open-ended question responses related to therapies and well-being. CONCLUSIONS: Access to pediatric rehabilitation therapies was disrupted during COVID-19. Disrupted access may be related to impact on physical and mental health. With the expansion of telehealth, caregiver and child feedback should be incorporated to optimize benefit.