Faculty Bibliography

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

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

Cognitive science research on learning and instruction is often not directly connected to discipline-based research. In an effort to narrow this gap, this essay integrates research from both fields on five learning and instruction strategies: active retrieval, distributed (spaced) learning, dual coding, concrete examples, and feedback and assessment. These strategies can significantly enhance the effectiveness of science instruction, but they typically do not find their way into the undergraduate classroom. The implementation of these strategies is illustrated through an undergraduate science course for nonmajors called Science in Our Lives. This course provides students with opportunities to use scientific information to solve real-world problems and view science as part of everyday life.

PURPOSE/OBJECTIVE:Neurogenic orthostatic hypotension is a prominent and disabling manifestation of autonomic dysfunction in patients with hereditary transthyretin (TTR) amyloidosis affecting an estimated 40-60% of patients, and reducing their quality of life. We reviewed the epidemiology and pathophysiology of neurogenic orthostatic hypotension in patients with hereditary TTR amyloidosis, summarize non-pharmacologic and pharmacological treatment strategies and discuss the impact of novel disease-modifying treatments such as transthyretin stabilizers (diflunisal, tafamidis) and RNA interference agents (patisiran, inotersen). METHODS:Literature review. RESULTS:Orthostatic hypotension in patients with hereditary transthyretin amyloidosis can be a consequence of heart failure due to amyloid cardiomyopathy or volume depletion due to diarrhea or drug effects. When none of these circumstances are apparent, orthostatic hypotension is usually neurogenic, i.e., caused by impaired norepinephrine release from sympathetic postganglionic neurons, because of neuronal amyloid fibril deposition. CONCLUSIONS:), a synthetic norepinephrine precursor, has shown efficacy in controlled trials of neurogenic orthostatic hypotension in patients with hereditary TTR amyloidosis and is now approved in the US and Asia. Although they may be useful to ameliorate autonomic dysfunction in hereditary TTR amyloidosis, the impact of disease-modifying treatments on neurogenic orthostatic hypotension is still uninvestigated.

Introduction: Psychological resilience is a dynamic process of positive adaptation to adversity based on maintenance of positive adjustments under challenging life circumstances. Multiple sclerosis is a chronic and unpredictable illness, accompanied by physical and emotional challenges, yet the role of psychological resilience in MS is understudied. We analyzed the impact of psychological resilience on disability measures in Multiple Sclerosis (MS).
Objective(s): To investigate the effect of psychological resilience on standard measures of disability in MS.
Aim(s): To assess a role of psychological resilience in MS.
Method(s): One hundred and one patients with relapsing-remitting MS: 52 African-American (AA) patients with mean age 38.56 +/- 11.05 yrs and mean disease duration 7.79 +/- 5.38 yrs and 49 Caucasian (CA) patients with mean age 38.92 +/- 10.43 yrs and mean disease duration 6.65 +/- 5.31 yrs were enrolled as part of an ongoing study. Psychological resilience was assessed with the Connor-Davidson Resilience Scale 10 item, a validated measure of psychological resilience. Partial correlations were evaluated between resilience and standard measures of disability in MS (Symbol Digit Modalities Test -SDMT, Nine Hole Peg Test- NHPT, Timed 25 Foot Walk -T25FW), controlling for demographics (age, gender, disease duration), disease burden (brain atrophy and T2 lesion volume), and depression.
Result(s): Psychological resilience was not related to demographics or disease burden however psychological resilience was related to depression (r=-0.65, p< 0.001). Psychological resilience was associated with better performance on SDMT (r=0.39, p=0.001) and NHPT (r=-0.31, p=0.010) with a trend toward significance on T25FW (r=-0.22, p=0.074). After controlling for demographics and disease burden, no difference in resilience or depression was seen between AA and CA patients. Stratified by race, higher psychological resilience was associated with better performance on SDMT (r=0.38, p=0.021) and NHPT (r=-0.43, p=0.008) in AA patients and on SDMT (r=0.46, p=0.019) and T25FW in CA patients (r=-0.42, p=0.035).
Conclusion(s): Our results show a positive impact of psychological resilience on disability in MS, independent from disease severity and mood changes. Identification of patients with lower resilience suggests potential targets for therapeutic intervention. Longitudinal studies are needed to confirm a protective effect of psychological resilience against MS disability

Objective: To investigate cognitive deficits in African Americans (AA) with MS.
Background(s): Cognitive impairment is one of the most frequent and burdensome symptoms of MS. Although a more severe disease course has been descibed in AA in comparison with Caucasians (CA) patients, an objective assessment of the cognitive profile of AA and potential differences with CA patients has not been investigated yet.
Method(s): Fifty-one AA patients (40F, mean age 38.45 +/- 11.13 yrs, mean disease duration 7.88 +/- 5.39 yrs), 37 AA healthy controls (HC) (25F, mean age 35.97 +/- 12.44 yrs), 43 CA patients (32F, mean age 39.00 +/- 10.56 yrs, mean disease duration 6.67 +/- 7.00 yrs) and 18 CA HC (12F, mean age 30.72 +/- 6.94 yrs) were prospectively enrolled as part of an ongoing longitudinal study. In all subjects, an extensive neuropsychological evaluation was performed, including: Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT), Brief Visuospatial Memory Test-Revised (BVMT), Stroop Color and Word Test (SCVT), Controlled Oral Word Association Test (COWAT), Pattern Comparison Processing Speed Test (PCPST) and a multitasking attention-memory test (MAMT). Each patient's group was compared with a race-matched HC group via ANCOVA analysis, accounting for age, gender, years of education, premorbid intelligence estimated with the Wechsler Test of Adult Reading (WTAR) and socioeconomic status expressed as yearly income.
Result(s): AA patients and HC did not differ in gender, age, years of education, WTAR score or socioeconomic status. CA patients and HC did not differ in gender, years of education and socioeconomic status, while significantly differ in age and WTAR scores (p=0.001 for both). Significant differences in SDMT (p=0.002), BVMT (p=0.012), COWAT (p=0.006), PCPST (p=0.008) and MAMT (p=0.018) scores were identified between AA patients and AA HC. Significant differences in SDMT (p=0.003), CVLT (p=0.009), BVMT (p=0.021), COWAT (p=0.003) and PCPST (p< 0.0001) scores were identified between CA patients and CA HC.
Conclusion(s): AA and CA patients showed similar deficits in information processing speed, attention, visuospatial memory and verbal fluency. CA patients showed additional impairment in the verbal memory domain, while AA patients showed deficits in multitasking capability. These results suggest that the cognitive profile of MS patients mostly overlaps across different races, although it seem to show group-specific deficits in specific domains

Continuous subcutaneous apomorphine infusion (CSAI) is a well-recognized therapeutic option for the management of motor fluctuations in Parkinson's disease (PD), although clinical experience suggests that most patients discontinue CSAI after a variable amount of time due to several causes and circumstances. The objective of the present study was to evaluate the reasons of CSAI discontinuation and to investigate which treatment was adopted afterwards. Two independent raters retrospectively reviewed the electronic medical record of 114 patients treated with CSAI for at least 6 months. The records were reviewed regarding efficacy, safety, and evolution of CSAI treatment. Most of PD patients on CSAI had a significant improvement in their clinical condition. Lack of improvement of dyskinesia was the most frequent causes of treatment discontinuation. The second reason for CSAI discontinuation was cognitive deterioration. At CSAI discontinuation, younger patients were more likely to undergo deep brain stimulation (DBS), while older patients and patients with cognitive impairment were more likely switched to oral therapy alone (OTA). CSAI is an effective treatment that unfortunately must be discontinued in a great number of patients with advanced PD. As older age is the main limiting factor for accessing second-level therapies at CSAI discontinuation, CSAI treatment should not be postponed to older age. CSAI might be considered a good first-line and fast strategy in patients undergoing rapid deterioration of their quality of life while waiting for DBS or levodopa/carbidopa intestinal gel therapy.

Introduction: A model of individual response to therapy based on demographic and clinical information ('The MSBase model'; Brain. 2017, 140:2426) improves clinicians' ability to predict how individual patient will fare on specific disease-modifying therapy (DMT) during a 4-year follow up period. However, the range of predicted outcomes is often too wide to make it the arbiter of decision- making. MS severity score (MSSS), a decile rank of Extended Disability Severity Scale (EDSS) scores in patients from the reference dataset, was shown to be longitudinally stable in MS cohorts, but not for individual patients.
Objective(s): To test whether the addition of MSSS will improve the accuracy and robustness of the existing MSBase predictive model.
Method(s): All eligible patients from the global MSBase cohort who commenced a new DMT during the prospectively recorded follow-up were included. For each DMT, Andersen-Gill survival models were constructed for confirmed disability and relapse events. Principal component analysis was used to reduce dimensionality of the models, as previously described. MSSS was added to these models separate from the principal components.
Result(s): Among 13,780 MSBase enrollees (72% female; 86% with Relapsing MS; age 38.4 [10.6] years, disease duration 8.49 [7.73] years, EDSS 2.65 [1.80]), the most common DMTs were Interferon (IFN)b-1a sc (18%), IFNb-1b sc (12%) and Glatiramer acetate (11%). Higher MSSS was associated with an increased chance of 6-month confirmed recovery from disability (Hazard ratio (HR) 1.17-1.64 p< 0.003; no evidence of association only for alemtuzumab) and with relapse risk (HR 1.03-1.18 p< 0.04, and non-significant for 3 DMTs), but did not predict risk of confirmed disability progression for any DMT. The amount of variance that MSSS helped to explain in addition to the original MSBase model was modest, largest for disability regression (partial adjusted R2 0.01-0.05) and less substantial for risk of relapses (partial adjusted R2 - 0.001-0.026).
Conclusion(s): Mostly independent of DMT identity, higher MSSS was positively associated with a chance of confirmed disability regression, and relapse risk, but not disability worsening. Addition of MSSS to the MSBase model yielded improvements in its predictive accuracy, especially with regard to disability regression and relapse risk. MSSS adds to the prediction of recovery from disability and relapse activity but is not a suitable indicator of individual treatment response