Faculty Bibliography

and Introduction Fatigue is a common and debilitating symptom of multiple sclerosis (MS) with estimates of up to 75% of patients reporting fatigue as their most disabling symptom [1]. Despite its prevalence, fatigue remains a frustrating symptom lacking reliable treatment options. tDCS has been previously shown to improve fatigue in MS patients, but requires daily sessions to be effective [2]. The necessity of daily sessions limits many studies to small sample sizes and few sessions studied, especially for patient populations with disability who may have additional physical barriers to attending daily sessions on top of personal and professional obligations. In response to this issue, we have developed a remotely-supervised tDCS (RS-tDCS) protocol that allows participants to complete tDCS sessions from home. The accessibility of our remote protocol increases both enrollment and compliance; moreover, it allows for an extended number of sessions to be studied [3]. Participants were enrolled in a RS-tDCS feasibility study in which they completed baseline, daily, and study-end measures of fatigue. 2. Methods This study was an open label, exploratory pilot study. Eligibility criteria were relatively broad, enrolling patients with a confirmed diagnosis of MS (all subtypes) between the ages of 18-70 years and a range of neurologic disability as measured by the Expanded Disability Status Scale (EDSS). Those with greater disability (EDSS >= 6.5) participated with the assistance of a caregiver proxy. Participants visited the clinic for baseline and follow-up measures. Here they completed self-report measures of fatigue, the Modified Fatigue Impact Scale (MFIS), and the PROMIS Fatigue measure (with lower scores associated with benefit). The baseline visit also consisted of tDCS training and the first of 10 sessions. Participants completed 9 daily tDCS sessions from home (20 minutes; DLPFC montage; left anodal) paired with brain training games. Before and after each session, participants rated their fatigue on a visual analogue scale. After all sessions were complete participants returned for a follow-up visit where baseline measures were repeated. Paired t-tests were used to analyze change in scores from baseline to follow-up. 3. Results A total of 25 participants were enrolled with all MS subtypes (n = 6 relapseremitting; n = 19 progressive) and a range of disability (EDSS scores ranged from 1.0 to 8.0). Most participants saw positive change in fatigue measures indicating an overall beneficial effect. Individuals' data points are shown in Fig. 1. Paired t-tests were performed to test for significance of the effect, summarized in Table 1. MFIS and daily fatigue measures showed significant improvement while PROMIS Fatigue did not. It is worth noting that n = 16 for the PROMIS Fatigue is due to its late introduction into the study, possibly reducing the power of that specific measure. 4. Discussion and Conclusion These data indicate RS-tDCS as a possible method for improving fatigue in patients with both relapsing-remitting and progressive MS. While benefit is shown to be significant in two of three fatigue measures, the benefit seems to be small. It is possible that higher amperage, more sessions, or longer sessions could bolster the effect we see. Further studies will look at dose-response and involve a sham arm to help validate findings. (Figure Presented)

Introduction One of the most reliably observed effects of transcranial direct current stimulation (tDCS)1 is improvement in working memory performance. However, emotional changes have yet to be thoroughly examined. The left dorsolateral prefrontal cortex (DLPFC) is considered to be a neural substrate of specific aspects of mood 2 and emotion3. For example, studies have shown that it influences emotional stimulus categorization3, emotional evaluation3, and emotional regulation4 and thus, is considered to have a major role in top-down emotional control. Here, we explored whether two emotional orthogonal dimensions, positive and negative affect5, differentially respond to left anodal tDCS using a DLFPC montage. As part of an open-label feasibility trial6, we observed mood changes in a sample of participants with multiple sclerosis (MS). Participants were recruited to develop a remotely-supervised or RS-tDCS protocol where they participated from home using videoconferencing and pairing with cognitively engaging exercises during the stimulation period. A control sample was recruited for comparison where the participants only completed the cognitive training exercise but not the tDCS, otherwise using the same remotely-supervised videoconferencing protocol. Methods Eligibility criteria were purposely broad in order to develop the RS-tDCS protocol, and participants were not recruited to treat any specific symptom (including mood). We enrolled patients with a confirmed diagnosis of MS (all subtypes) between the ages of 18-70 years. Active participants were enrolled in an open label treatment study (RS-tDCS paired with cognitive training), while controls were recruited separately and completed the cognitive training only. Participants visited the clinic for baseline and follow-up measures. After initial training, they completed 9 remotely-supervised sessions from their homes, consisting either of active (1.5 mA stimulation) paired with the cognitive training (CT) or CT alone. Mood outcome was measured with the self-reported Positive and Negative Affect Schedule 7, with scores of Positive Affect (PA) and Negative Affect (NA). Results A total of n=24 participants completed the active condition including the PANAS at both time points and were compared to n=20 in the comparison condition. Groups were generally equivalent (Table 1). Paired t-tests indicated that PA trended towards significant improvement in the active condition only (mean change in PA = -3.2+/-8.3, p=0.07 vs. -1.0+/-5.8, p=0.45) while both groups showed similarly significantly lowered levels of NA (mean change in NA = 5.1+/-7.2, p=0.002 vs. 4.2+/-5.6, p=0.003). As shown in Fig. 1, the proportion of change from baseline to study end across individuals was disproportionately greater for the active condition for PA, while NA remained the same. For both groups, change in NA was significantly predicted by baseline NA, indicating that the higher the NA the more likely for improvement (r's = 0.68 and 0.67 for active and control groups respectively, p's<0.001). However, change in PA was predicted by baseline NA (and not PA) only in the active condition (r=0.48, p=0.02). Discussion: In this study, exploratory analyses indicated that DLPFC (left anodal) tDCS differentially improves PA compared to NA in MS participants. These findings are consistent with the presumed neurobiological substrates of PA but not NA in the dorsolateral and ventromedial frontal regions. This is supported by PA improvements being independent from baseline PA levels, suggesting a broad and beneficial effect of stimulation to the DLPFC region. Of note, both conditions had significant reductions in NA across the 10 sessions. Thus, shared features of the cognitive training and contact with the study technician through videoconferencing at each session may have served to generally reduce features of negative affect. This is supported by higher levels of baseline NA predicting a response, indicating a decrease in features such as irritability and anxiousness as part of general participation in the study. Future studies will utilize neuroimaging to confirm targeted engagement of the DLFPC in order to enhance changes in mood with tDCS in MS participants. We will also characterize changes in mood in participants with clinically significant mood problems at baseline. We hope that tDCS treatment may be generalizable across conditions. (Figure Presented)

and Introduction Cognitive and motor deficits are common debilitating symptoms for individuals living with Parkinson's disease (PD). The severity of cognitive and motor impairment in PD is associated with disease burden and quality of life. (1, 2) Transcranial direct current stimulation (tDCS) is a recent therapeutic development with the potential to ameliorate symptoms of PD. Previous studies have associated tDCS with improvement in motor and cognitive function in patients with PD. (3) However, multiple treatment sessions are necessary for a cumulative benefit. The requirement to travel for daily clinic treatment sessions presents an obstacle for many patients, especially those with higher disability and limited access to transportation. In addition to restricting patient access to repeated treatment sessions, such challenges have also limited the design of clinical trials in PD to date. Recently, we have developed a remotely supervised tDCS (RS-tDCS) protocol that delivers computerized cognitive training (CT) paired with tDCS to individuals with MS. (4) Using the same protocol with extensive safety measures, well-defined guidelines, and specially-designed equipment, we explored the feasibility and adaptability of our RS-tDCS approach for participants with PD. 2. Methods This study was an open-label feasibility study. The eligibility criteria were relatively broad, with the key factors being a definite diagnosis of PD, PD-related changes to cognitive functioning, adequate home facilities, and a score of >= -3 standard deviations on the Symbol Digit Modalities Test (SDMT(5)) to measure disease-related cognitive decline and to ensure that participants had the cognitive ability to understand and participate in study procedures. Each participant completed 10 tDCS sessions (20-minute each, 1.5-2.0-mA, dorsolateral prefrontal cortex or DLPFC montage, which has been verified for effective targeted engagement of fatigue in patients with PD(6), over a span of two weeks using the remotely-supervised protocol. After the initial session at baseline, participants were sent home with a study laptop and tDCS equipment. The tDCS device (Soterix Mini-CT) is dependent on a code to operate, delivering a single 20 minute "dose" per code. All sessions were supervised in real-time using videoconferencing. The tDCS study technician ensured that the headset was correctly placed before providing the single-use activation code for the session. Additionally, study technicians followed a decision-tree series of checkpoints with "STOP" criteria set forth in the protocol that must be cleared in order to proceed at each step. These checkpoints address compliance (attendance and ability to complete the procedures as instructed) and tolerability (if any predefined events are reported at any time or if pain crosses a threshold, participation will be discontinued). For each study session, participants in both conditions were asked to complete a self-report inventory of adverse events and common side effects before and after their sessions (with items derived from a list of the most common tDCS side-effects in previous trials.(7) During the stimulation sessions, participations completed cognitive activating tasks on the computer. Feasibility of the approach was assessed based on the aforementioned series of checkpoints to address attendance, tolerability, and safety of the sessions. 3. Results A total of 50 sessions were completed with 100% compliance. In comparison to the MS sample (n=20) in our RS-tDCS pilot study, the PD participants (n=5) are significantly older (mean = 45.15 in MS vs. mean = 69.80 in PD, p=0.004). The PD cohort exhibited a slightly lesser degree of cognitive impairment in their corresponding age groups as measured by the SDMT (mean z-score = -0.94 in MS vs mean z-score = -0.66 in PD, p=0.90). However, this may be influenced by the higher level of education (mean = 17.4 years) achieved by participants in the PD cohort compared to those in the MS cohort (mean = 15.95 years, p = 0.21), and in addition, inter-individual variability will prominently influence a sample's demographic and disease feature composition in a smaller sample size. All participants were able to quickly learn self-administration. In addition, our RS-tDCS protocol provided the opportunity to coordinate sessions with participants' anti-PD medications, ensuring that CT-paired stimulation could occur within the crucial 1-3 hour time window post-medication for maximum benefit (as recommended by study physicians at the New York University Fresco Institute for Parkinson's and Movement Disorders). No serious adverse events were reported. The most commonly reported side effects were skin tingling and burning sensations. The most intense side effect was a burning sensation at an intensity of 4, which qualifies as "mild" on scale from 1 [minimal] to 10 [severe]. The intensity and duration of time that these side effects were noticed by participants tended to decrease throughout the study. Across the 50 sessions, 96% of the daily self-reported pain ratings related to stimulation that were taken before, mid-way, and after tDCS stimulation were reported as 0, which denotes "no pain" on the visual analog scale ranging from 0-10 that participants used to rate pain from the headset. RS-tDCS range of 1.5-2.0mA was tolerable for all participants in the study. 4. Discussion and Conclusion The RS-tDCS protocol was originally developed and tested in MS participants but designed to be appropriate for more generalizable use. Here, we expand the RS-tDCS protocol for use in PD. The study's high rate of compliance indicates that RS-tDCS is a safe and feasible approach for delivering direct current stimulation for individuals with PD, as with MS, despite the older age of our cohort of participants with PD. Across all 50 sessions, participants with PD found the stimulation to be tolerable. Key concerns for implementing RS-tDCS as an at-home treatment for PD include overall apprehension of technology and the need for technological support among this cohort, given the advanced age range and disabilities. Overall, the data indicate that RS-tDCS is easily implemented to accommodate participants' medication schedules, as well as physical therapy and exercise schedules, to provide maximum benefit and convenience. These findings support the use of the RS-tDCS protocol for clinical study in PD and other movement disorders, as well as the generalizability of the RStDCS approach for participant cohort with varying neurological diseases aside from MS

Transcranial direct current stimulation (tDCS) is a promising therapy with a growing number of applications. However, clinical studies to date have been limited by small sample sizes and few sessions studied. To increase enrollment and extend treatment, we developed a protocol for remotelysupervised or RS-tDCS to enable participants to receive treatment from home while monitored in real-time.1, 2 Here we present the findings of two studies in multiple sclerosis (MS), the first being an open label feasibility study with 1.5mA x 20 minutes and the second being a randomized, controlled clinical trial of active 2.0mA or sham x 20 minutes. In addition, we have extended the protocol for use in Parkinson's disease (PD), completing 10 open-label 2.0 mA sessions x 20 minutes. All sessions were performed using a dorsolateral prefrontal cortex montage (DLPFC) and were paired with cognitive training tasks. This study adds to previous safety evidence.3 Methods Eligibility criteria were purposefully broad in both studies to assess the feasibility of a remote-supervision protocol . The criteria required that patients had a definite diagnosis of MS (all subtypes), were between the ages of 18-70, had no history of serious brain trauma, and were physically, visually, and cognitively competent enough to perform study procedures. Additonally, participants were required to enroll in the study with a healthcare proxy if their disability was greater than an Expanded Disability Status Scale (EDSS) Score of 6.5. Eligibility criteria for the Parkinson's Disease (PD) cohort was similar to the MS criteria, albeit with a larger age range for participation (30-89) and without the EDSS score requirement. The RS-tDCS protocol included a baseline screening and tolerabilty test, followed by training in device operation. Participants were then sent home with a study kit that included a laptop computer and tDCS equipment. Each remote session was selfadministered with guidance from a study technician, while constant supervision was maintained via videoconferencing. Extensive safety and stop criteria were followed to prevent any adverse events or misuse. The studies used the Soterix Mini-CT device that delivered a 20 minute session of a specific current "dose" or sham, based on a preprogrammed one-time use code that was provided by the study technician at each session. Safety and tolerability were measured by assessing both experiences of minor adverse events and pain ratings. Following each session, participants were asked if they had experienced any adverse events, which were read aloud froma list of those most commonly reported. Pain ratings (using a visual analogue scale, 1-10) were measured before, during, and after each session. Any participants experiencing pain or adverse events above an intensity of seven were discontinued from the study as per study protocols. Study 1 MS participants (n=26) were recruited between the dates of March 2015 and February 2016 at the Lourie Center for Pediatric MS at Stony Brook University. This trial was an open-label study and all participants knowingly received the active tDCS therapy. 1.5mA of tDCS therapy was administered for 20 minutes each day for 10 days. Study 2 Participants with MS (n=15) were recruited between January 2016 and September 2016 at the MS Care Center at New York University Langone Medical Center. This study is an ongoing, actively recruiting, randomized, double-blinded, controlled clinical trial using RS-tDCS. All MS patients were randomized to either the active condition (20 minutes of 2.0mA tDCS) or the sham condition. The sham condition served as the control in this study and aimed to deceive participants into believing they were receiving the 20 minutes of tDCS by ramping up at the first minute of the session and ramping down at the last minute of the session. All participants who received the sham condition were offered 10 sessions of 2.0mA open-label tDCS following completion of 20 sessions of sham. Study 3 Participants with PD (n=4) were recruited between the dates of June 2016 and October 2016 at the Fresco Institute for Parkinson's and Movement Disorders at the New York University Langone Medical Center. Using the aforementioned remotelysupervised protocol established for MS, participants in the PD cohort received openlabel 2.0 mA tDCS for 10 sessions to assess the feasibility and generalizability of the remotely-supervised protocol for this new cohort. Results Study 1 Patients with MS (n=26) were recruited and completed study procedures. Two patients were discontinued during the course of the study. The first of the two was discontinued due to personal obligations, and the second was discontinued due to extreme sensations of skin burning (8.5/10 on the analogue scale) without any physical burns. The burning sensation did not continue after termination of the session. Overall, 248 sessions were successfully completed with this cohort. Study 2 Patients with MS (n=17) were recruited and completed study procedures. Only one participant was discontinued from the blinded active condition due to serious headaches at an intensity above 7. One participant who was originally assigned to the sham condition and who opted for the extended, open label sessions voluntarily withdrew due to resurgence of headaches (the headaches did not meet our criteria of discontinuing the patient). 147 sessions of the active 2.0 blinded condition were succesfully completed. 135 shammed sessions were successfully completed. 54 sessions of the open-label, extended sessions following sham were completed. Study 3 Participants with PD (n=4) were recruited and completed study procedures. No participants voluntarily withdrew from this cohort nor were any discontinued. 40 sessions were successfully completed. In total, 624 sessions have been completed using the RS-tDCS protocol. Three participants have been discontinued and one has voluntarily withdrew from the study. Participants who were discontinued due to adverse events found that they reverted to their baseline state when terminating the intervention. The percent of adverse events experienced is presented below in Fig. 1. This Figure does not include information regarding the intensity or duration of the adverse events experienced. Instead, it reports the frequency of advese events experienced, which accounts for the high incidence rate of adverse events in the sham condition. Table 1 accounts for the intensity of the most commonly reported adverse events. The table also includes the number of adverse events reported relative to the number of total sessions. On average, an intensity above 3 was not reported for any of the most common adverse events in any stimulation condition. Discussion The RS-tDCS protocol is safe and tolerable in both MS and PD participants, and continues to lead to high rates of compliance with treatment sessions. No serious adverse events have been reported. The most common side effects reported are skin tingling and itching. Of note, across conditions, the 1.5mA open label condition reported the highest rates of side effects. This may be accounted for by open-label treatment, where participants may have been more focused on potential effects of the stimulation. The 2.0mA open label condition may not be as comparable to the 1.5mA open label condition due to a smaller sample size in the 2.0mA condition. Over all, none of the adverse events were severe, with intensity below 3 on a visual analogue scale of 1-10. Both 1.5 and 2.0mA tDCS are safe and tolerable forms of treatment in both MS and PD, and may be generalizable for clinical study in a wide range of neurologic and psychiatric disorders. (Figure Presented)

Objective: To explore the feasibility and safety of remotely supervised transcranial direct current stimulation RS-tDCS) paired with computerized cognitive training exercises in participants with Parkinson's disease (PD). Background: tDCS is a recent therapeutic development with potential to ameliorate symptoms of PD including motor, sensory, mood, and cognition.. However, multiple treatment sessions are necessary for a cumulative benefit. The requirement to travel to the clinic for daily clinic treatment sessions has limited the design of clinical trials in PD to date. Here, we used a RS-tDCS protocol validated for use in patients with multiple sclerosis (MS), a condition that shares with PD significant impairment in mobility, cognition, and high prevalence of fatigue. Design/Methods: Each participant completed 10 tDCS sessions (20-minute each, 1.5-2.0-mA, dorsolateral prefrontal cortex montage) using the remotely-supervised protocol. Feasibility of the approach was assessed based on a series of checkpoints, addressing attendance and tolerability and safety of the 40 sessions paired with simultaneous CT. Results: A total of 40 sessions were completed with 100% compliance. All participants were able to quickly learn self-administration and the set up time decreased through the 10 sessions for those who struggled with set up in the beginning. No serious adverse events were reported. Most commonly reported side effects were skin tingling and burning sensation. The most intense side effect was burning sensation at intensity of 4, which qualifies as "mild" on scale from 1 [minimal] to 10 [severe]. Time that these side effects were noticed by participants throughout the duration of the study also tended to decrease. RS-tDCS range of 1.5-2.0mA was tolerable for all participants Conclusions: RS-tDCS was feasible and safe in PD participants and can be paired with tele-rehabilitation. This study encourages using this innovative protocol for larger studies and clinical trials in PD patients

Objective: To evaluate whether tDCS improves fatigue in MS and the role of baseline affect in response, using a remotely-supervised telerehabilitation protocol. Background: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that alters cortical excitability through low amplitude currents. Previous work suggests tDCS as a method for symptomatic management in MS. However, these initial studies have been limited due to small sample sizes and few active treatment sessions. Design/Methods: Participants completed ten 20 minute sessions of tDCS (1.5 mA, dorsolateral prefrontal cortex, left anodal) paired with cognitive training. Sessions were completed from home using our RS-tDCS protocol. All participants completed baseline and follow-up mood and fatigue self-report measures including the Modified Fatigue Impact Scale (MFIS) and the Positive and Negative Affect Schedule (PANAS). Baseline positive affect (PA) and negative affect (NA) were z-transformed and averaged into a representative affect score. Results: Participants (n=25) aged 30 to 69 years with a range of impairment (Expanded Disability Status Scale (EDSS) scores of 1.0 to 8.0) and all subtypes were enrolled. RS-tDCS treatment led to clear improvements in both dimensions of affect (PA, Cohen's d = 0.32 and NA, d = -0.66) and fatigue (MFIS, d = -0.59). Participants' baseline affect score correlated with change in NA (r = 0.61, p < 0.01) and MFIS (r = 0.39, p = 0.06). Among participants who had a baseline affect z-score less than 0 (n=17) indicating affect disturbance, there was a greater magnitude of improvement and significant change from baseline (PA, d = 0.57, p=0.02; NA d = -1.07, p < 0.001; and MFIS d = -0.84, p<0.01). Conclusions: Telerehabilitation using RS-tDCS improves mood and fatigue in MS patients treated at home, with greater effects found in those with baseline features of mood or anxiety

Objective: To test whether home delivery of tDCS paired with cognitive training can improve cognitive outcomes in participants with multiple sclerosis (MS). Background: Cognitive impairment is a common debilitating MS symptom. Transcranial direct current stimulation (tDCS) paired with cognitive training presents itself as a possible option for those with cognitive impairment, but requires daily sessions, placing strain on patients. Here we explore the feasibility and efficacy of a remotely- supervised tDCS protocol (RS-tDCS) paired with cognitive training for patients with MS. Design/Methods: MS participants completed 10 sessions of tDCS paired with cognitive training (1.5 mA x 20 minutes, dorsolateral prefrontal cortex montage). RS-tDCS participants were compared to a control group of adults with MS who underwent ten 20-minute cognitive training sessions through the same remotely-supervised procedures. Cognitive outcomes were tested by composite scores measuring change in performance on standard measures (Brief International Cognitive Assessment in MS or BICAMS), basic attention (Attention Network Test-Interaction (ANT-I) Orienting and Attention Networks, Cogstate Detection), complex attention (ANT-I Executive Network, Cogstate Identification and One-Back), and intra-individual response variability (ANT-I and Cogstate identification). Results: After ten sessions, the RS-tDCS group (n=25) compared to the control group (n=20) had significant improvements in complex attention (p = 0.01) and response variability (p = 0.01) composites. The groups did not differ in change of measures of basic attention (p = 0.95) or standard BICAMS cognitive measures (p = 0.99). Conclusions: RS-tDCS paired with cognitive training is effective for enhancing complex attention and reducing response variability. The benefit of telerehabilitation using RS-tDCS combined with cognitive training may be generalizable to other conditions

Objective: To test whether the Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) predicts real-world functioning as measured by timed instrumental activities of daily living (ADLs). Background: The BICAMS is a cognitive screen that is widely-used in clinical practice and research to assess cognitive impairment in persons with multiple sclerosis (MS). It is important for cognitive measures to predict daily functioning. We compared performance on the BICAMS to a test consisting of ten timed instrumental activities of daily living, called the Test of Everyday Cognitive Ability or TECA. Design/Methods: All participants were administered the TECA along with three BICAMS measures: Symbol Digit Modalities Test (SDMT), the Brief Visuospatial Memory Test-Revised (BVMT-R), and either the Rey Auditory Verbal Learning Test (RAVLT) or substituted with the Selective Reminding Test (SRT). The TECA items were scored according to time and errors and averaged for one representative score, with higher scores indicating greater impairment. BICAMS measures were transformed to age-normative z scores for comparison, with scores of <-1.5 considered impaired, and one or more impaired scores indicating overall BICAMS impairment. Results: A total of n=177 MS patients (mean age 45+/- 14 years, 73% female) with a median EDSS=3.0 (range of 0.0 to 8.0) completed the study. Overall, 37% met BICAMS impairment criteria. Each of the individual BICAMS measures significantly predicted performance on the TECA: SDMT, r=-.53, p<.001, BVMT-R r= -0.32, p <0.001, and Verbal Learning r= -.34, p <0.001. Worse TECA scores were associated with poorer performance on the BICAMS. Conclusions: The TECA is a measure of timed instrumental activities of daily living that is valid for use in a diverse MS population. BICAMS significantly predicts performance on the TECA, indicating that it is a useful indicator of real-world functioning

Objective: Speeded Saccadic Eye Movement Predicts Symbol Digit Modalities Test Performance in Multiple Sclerosis Background: Multiple sclerosis is an autoimmune demyelinating disease with estimates of cognitive impairment above 30% in pediatric and 50% in adult patients. The SDMT, a widely-used screening tool that measures speeded information processing, has been used to track cognitive decline in MS. The K-D test is a brief measure of saccadic eye movement speed using a timed number naming test, commonly used for the detection of mild traumatic brain injury. Here, we tested the sensitivity of the K-D test in MS and its association with performance on the SDMT. Design/Methods: Adult and pediatric patients with clinically-definite MS were consecutively recruited through the NYU Langone MS Comprehensive Care Center. All participants completed the SDMT and K-D at a single visit. Results: A total of 30 participants completed the assessments ranging in age from 13 to 72 years (mean 38 +/- 19 years), were 74% female, and with an EDSS range 0.0 to 6.5. Relative to age normative data, the K-D indicated greater impairment than the SDMT (74% vs. 48%, respectively). Controlling for age, both tests were significantly correlated (r=0.44, p =0.02), demonstrating a close contribution of oculomotor function to SDMT performance. Conclusions: The K-D test is sensitive to detecting impairment in MS across the lifespan. Performance on the SDMT is closely associated with oculomotor function in MS

Objective: To test whether changes in fine motor speed predict change in cognitive functioning in pediatric onset MS (POMS). Background: Multiple sclerosis is an autoimmune demyelinating disease that has a pediatric (<18 years) onset in 3-5% of all cases. Cognitive impairment is a frequent and disabling symptom for approximately 30% of POMS patients. As in adults, the earliest cognitive involvement can be measured by the Symbol Digit Modalities Test or SDMT, a measure of speeded information processing. Fine motor slowing occurs frequently in both adult and pediatric patients, but its relation to cognitive functioning remains unclear. The Lafayette grooved pegboard serves as a measure of fine motor functioning and has previously been shown to be sensitive in MS samples. Design/Methods: POMS patients were consecutively recruited through the Lourie Center for Pediatric MS and the NYU Langone MS Comprehensive Care Center. All participants completed the SDMT and the Lafayette grooved pegboard (dominant and non-dominant hand conditions) at two separate visits (using an alternate form for the SDMT). Both SDMT and pegboard performances were transformed to age-normative z scores for comparison. Results: A total of n=26 POMS participants completed both assessments. The mean age was 16.5+/-3.08 years and 58% were female. The mean time between study visits was 193+/-148 days. Both measures improved at repeat administration, with mean SDMT and pegboard z scores improving from 0.11+/-1.39 to 0.34+/-1.41 and -1.56+/-1.68 to -1.21+/-2.55, respectively. Change in pegboard performance significantly predicted change in the SDMT (r=0.58, p=0.002)