Faculty Bibliography

BACKGROUND/UNASSIGNED:Cognitive impairment occurs in approximately one-third of pediatric-onset multiple sclerosis (POMS) patients. The Symbol Digit Modalities Test (SDMT), a widely used cognitive screen in adults, has yet to be incorporated early into the standard care of POMS. OBJECTIVE/UNASSIGNED:To screen for cognitive impairment early in the course of POMS and analyze predictive factors. METHODS/UNASSIGNED:Of the 955 POMS or clinically isolated syndrome (CIS) patients prospectively assessed from March 2014 to July 2018, 500 POMS and 116 CIS patients met inclusion criteria (disease onset before the age of 18, one or more SDMTs, and 8 years or older at the time of testing). Those with relapse were analyzed separately from those who were relapse-free. RESULTS/UNASSIGNED: = 383, mean follow-up: 1.8 years), 14.1% had clinically meaningful decline predicted by older age of multiple sclerosis (MS) onset and male gender. Disease relapse or steroid use led to transient worsening on the SDMT. CONCLUSION/UNASSIGNED:Early in the disease, some POMS and CIS patients are at risk for cognitive impairment and subsequent decline.

This paper updates guidelines for effective treatments of children with specific types of acquired brain injury (ABI) published in 2007 with more recent evidence. A systematic search was conducted for articles published from 2006 to 2017. Full manuscripts describing treatments of children (post-birth to 18) with acquired brain injury were included if study was published in peer-reviewed journals and written in English. Two independent reviewers and a third, if conflicts existed, evaluated the methodological quality of studies with an Individual Study Review Form and a Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Strength of study characteristics was used in development of practice guidelines. Fifty-six peer-reviewed articles, including 27 Class I studies, were included in the final analysis. Established guidelines for writing practice recommendations were used and 22 practice recommendations were written with details of potential treatment limitations. There was strong evidence for family/caregiver-focused interventions, as well as direct interventions to improve attention, memory, executive functioning, and emotional/behavioural functioning. A majority of the practice standards and guidelines provided evidence for the use of technology in delivery of interventions, representing an important trend in the field.Abbreviations: ABI = acquired brain injury, ACRM = American Congress of Rehabilitation Medicine, ACT = Acceptance and Commitment Therapy, Amat-c = Amsterdam Memory and Attention Training for Children, BRIEF = Behaviour Rating Inventory of Executive Function, BRIEF-MI = The Behaviour Rating Inventory of Executive Function Metacognitive Index, CAPS = Counselor Assisted Problem-solving, CBT = cognitive behaviour therapy, COPM = Canadian Occupational Performance Measure, CO-OP = Cognitive Orientation to daily Occupational Performance, CRP = Cognitive Remediation Program, EBR = Evidence-Based Review, FPS = Family Problem-solving, IRC = Internet Resource Comparison, JBI = Joanna Briggs Institute, mTBI = mild traumatic brain injury, SSTP = Stepping Stones Triple P, SMART = Strategic Memory Advanced Reasoning Training, TBI = traumatic brain injury, TOPS = Teen Online Problem-solving, TOPS-TO = Teen Online Problem-solving-Teens Only, WM = Working Memory.

Background: Walking impairments are one of the most impactful consequences of multiple sclerosis (MS). Recently, physical rehabilitation research has focused on developing synergistic protocols to enhance clinical benefit. Recent studies have shown that transcranial direct current stimulation (tDCS) and aerobic physical activity (PA) have converging activation pathways and when completed simultaneously, they may promote cortical neuroplasticity.
Objective(s): To harness cortical plasticity to improve gait for individuals with MS.
Aim(s): To investigate the effects of multiple sessions of PA with simultaneously administered tDCS on walking abilities.
Method(s): MS participants (EDSS: 1-6.5, Relapsing-Remitting or Secondary-Progressive subtype) with clinically significant gait deviations were recruited for a randomized controlled trial of 10 sessions of either active or sham tDCS paired with unloaded cycling for 20 minutes. Stimulation was administered over the primary motor cortex (2.5 mA-2.0 mA; anode over C3/cathode over FP2). Walking speed was assessed quantitatively by using a single inertial sensor placed on the lower back and perceived walking abilities were evaluated using the 12-Item MS Walking Scale (MSWS-12), a self-report questionnaire. Measurements were collected at baseline, the end of tDCS intervention, and 4-weeks post-intervention. Two-way repeated measures-ANOVA (Time, Treatment) was performed to investigate differences between active and sham conditions.
Result(s): Thirty-two participants were enrolled in the study, 22 underwent active treatment. No demographic differences were detected between active and sham groups (active:EDSS 4.3+/-1.2, age 55.5+/-10.3; sham:EDSS 4.5+/-1.5, age 49.7+/-13.9). Statistical analysis showed significant Treatment by Time interactions for gait speed and MSWS-12 score. Post-hoc analysis revealed that gait speed increased significantly after active treatment (Baseline vs. End Treatment, 0.98 vs. 1.16 m/s, p< 0.001; Baseline vs. Follow-up, 0.98 vs. 1.20 m/s, p< 0.001). Active group further reported significant improvement in self-report measure (Baseline vs. End Treatment, 58.04 vs. 49.73, p< 0.05). No significant difference was detected after sham stimulation.
Conclusion(s): Our results indicate that multiple sessions of tDCS administered simultaneously with PA induce cumulative and selfreport improvement in walking and benefits persisted until 4-week post-intervention

Introduction: Cognitive impairment in pediatric onset multiple sclerosis (POMS) occurs in up to one third of cases.
Objective(s): To screen for cognitive impairment early in the disease course of POMS, measure predictive factors, and determine the effect of relapse on cognitive processing speed.
Aim(s): To identify cognitive processing speed impairment among POMS and pediatric clinically isolated (CIS) patients enrolled in the US Pediatric MS and Other Demyelinating Disease Registry. In March 2014, the Symbol Digit Modalities Test (SDMT) scores were analyzed from March 2014, when the SDMT was added to the clinical evaluation through July 2018, when the data set was locked.
Method(s): SDMT raw scores were converted to age-normative z-scores using validated age and sex adjusted means. Processing speed impairment was defined with z-score increments of-1.0. Clinically meaningful decline in longitudinal analyses was defined by a z-score decrease of 1.0 or more.
Result(s): For the POMS (n=500) and CIS (n=116) with at least one SDMT, the mean age at symptom onset was 13.5 years and the mean (+SD) disease duration at the initial SDMT assessment was 3.0 + 2.9 years. A total of 23.4% of MS and 16.4% of CIS patients had impaired processing speed at initial assessment. SDMT impairment was predicted by worse EDSS, longer disease duration, and lower level of mother's educational achievement. On longitudinal follow-up (n=383, mean follow-up: 1.8 years), 14.1% had clinically meaningful decline predicted by older age of MS onset, male gender, and longer test-retest interval. Disease relapse and steroid use were associated with transient SDMT worsening.
Conclusion(s): Early in the disease course, a subgroup of POMS patients are at risk for cognitive impairment and subsequent decline. Screening for cognitive slowing is critical for prompt identification of potential cognitive deficits and initiation of additional services

Introduction: Travel to clinic can be difficult due to barriers of time and cost and becomes even more burdensome for MS patients living with disabilities. Telemedicine platforms present a solution by providing supervised treatment and rehabilitation at home. Without barriers to access, patients may be more compliant and adherent to daily rehabilitation exercises. We have a large telerehabilitation research program in MS that pairs rehabilitation with transcranial direct current stimulation (tDCS), an emerging non-invasive brain stimulation technique used to improve outcomes. We provide real-time treatment administration and supervision via HIPAA compliant videoconference, termed remotely supervised tDCS or RS-tDCS.
Objective(s): To characterize the advantages of telemedicine for patients with MS in an urban setting.
Aim(s): To measure barriers to access for participants in our RS-tDCS telerehabilitation program, as well as compliance and adherence to a remotely supervised intervention.
Method(s): Participants with MS were recruited to complete a trial of cognitive remediation paired with RS-tDCS at-home. Participants were surveyed following completion of the intervention and asked to rate their difficulty in attending the clinic (on a 1-5 ordinal scale, 1 = no difficulty and 5 = nearly impossible difficulty) as well as the typical cost of attending clinic. Descriptive statistics and ordinal logistic regression models were used to evaluate the factors driving difficulty of travel.
Result(s): Participants (n=44) reported that round trip travel to the clinic requires an average of 2.3+/-2.3 hours of time and $27.04+/-38.13. Participants rated the difficulty associated with attending clinic as being moderate to significant (2.5+/-1.3). Regression analyses that included disease features produced better models and accounted for greater variance in difficulty attending the clinic, (p< 0.001, McFadden pseudo R2 = .515), as compared with socioeconomic variables alone (p< 0.001, McFadden pseudo R2 = .140). The RS-tDCS protocol was successful in providing treatment (95% compliance to treatment) and 93% of participants reported satisfaction with the treatment and remote protocols.
Conclusion(s): Participants with MS face considerable difficulty reaching the clinic, largely due to increasing neurologic disability. Telemedicine techniques such as RS-tDCS can increase treatment access, reduce physical and financial burden of travel and maintain high rates of treatment adherence

OBJECTIVE:Critical decisions regarding resection boundaries for epilepsy surgery are often based on results of electrical stimulation mapping (ESM). Despite the potentially serious implications for postoperative functioning, age-referenced data that might facilitate the procedure are lacking. Age might be particularly relevant, as pediatric ESM studies have shown a paucity of language sites in young children followed by a rapid increase at approximately 8-10 years. Beyond adolescence, it has generally been assumed that the language system remains stable, and therefore, potential age-related changes across the adult age span have not been examined. However, increasing age during adulthood is associated with both positive and negative language-related changes, such as a broadening vocabulary and increased word finding difficulty. Because most patients who undergo ESM are adults, we aimed to determine the potential impact of age on the incidence of ESM-identified naming sites across the adult age span in patients with refractory epilepsy. METHODS:We analyzed clinical language ESM results from 47 patients, ages 17-64 years, with refractory dominant-hemisphere epilepsy. Patients had comparable location and number of cortical sites tested. The incidence of naming sites was examined as a function of age, and compared between younger and older adults. RESULTS:Significantly more naming sites were found in older than younger adults, and age was found to be a significant predictor of number of naming sites identified. SIGNIFICANCE/CONCLUSIONS:Unlike the developmental changes that coincide with increased naming sites in children, increased naming sites in older adults might signify greater vulnerability of the language system to disruption. Because preservation of language sites can limit the extent of the resection, and thereby reduce the likelihood of seizure freedom, further work should aim to determine the clinical relevance of increased naming sites in older adults.