Faculty Bibliography

Objective: To examine whether a history of childhood adversity (i.e. abuse, dysfunction) influence clinical features of multiple sclerosis (MS) in adult patients. maltreatment, and household Background: Multiple epidemiological studies have linked adverse childhood experiences to changes in brain structure and stress-responsive physiologic mechanisms. Such changes have been found to profoundly increase risk for chronic disease, poorer emotional and social functioning, and cognitive impairment in adulthood. However, the specific role of these experiences in MS remains unclear. Design/Methods: Participants with MS were recruited from a cohort that previously completed a larger cognitive remediation trial. Measures included the Adverse Childhood Experience (ACE) and Resilience Questionnaire (RQ) self-report inventories. ACE and RQ scores were compiled into a composite score to provide a more comprehensive measure of endured childhood adversity, and these measures were compared to individual disease features. Results: A total of 76 participants completed the study (mean age 49.8+/-12.5 and 80% female). ACE scores were significantly and inversely correlated with RQ scores (r = -0.46, p<0.001), suggesting that greater childhood adversity corresponds with poorer psychological resilience. ACE, but not RQ, significantly predicted age of onset (r= -0.31, p=0.03 and r= -1.91, p=0.18 respectively). Both ACE and RQ were linked to estimated premorbid cognitive functioning (r= -0.30, p=0.009 and r= -0.27, p=0.02). However, the composite score of both measures offered the strongest predictive value for the impact of childhood adversity on age of onset (r= -0.31, p=0.02) and premorbid cognitive functioning (r = -0.32, p=0.005). Neither ACE nor RQ were related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT). Conclusions: Cumulative stress due to adverse childhood experiences and decreased psychological resilience may increase the likelihood of earlier MS onset and predict poorer premorbid cognitive functioning in adulthood

Objective: To test the relation between intra-individual variability (IIV) and cognition across the lifespan in multiple sclerosis (MS). Background: The Symbol Digit Modalities Test (SDMT) is a widely-used screen of cognitive functioning in MS across the lifespan. IIV in reaction time is a novel index of consistency across sustained performance. IIV been shown to be highly sensitive to general CNS integrity and global morbidity, and may serve as a cognitive biomarker in MS. Design/Methods: Patients with clinically-definite MS were recruited through the Lourie Center for Pediatric Multiple Sclerosis and the NYU Langone MS Comprehensive Care Center. Healthy controls were recruited for comparison purposes and utilized for the creation of the linear model that is necessary to calculate IIV scores. The SDMT and Cogstate Brief Battery were administered to all participants. The Cogstate Brief Battery consists of simple and choice reaction time tasks from which reaction time IIV was calculated. Results: A total of 187 MS participants completed the assessments ranging in age from 8 to 68 years (mean 32.9+/-17.6 years). Mean detection and identification IIV was calculated across the Cogstate reaction time measures, and predicted performance on the SDMT (r= -0.394, p<0.001). When compared to healthy controls, the effect sizes were nearly equivalent (Cohen's d = 0.53 and SDMT = 0.55, respectively). Conclusions: IIV in reaction time tasks may be used as a sensitive measure of performance variability in patients with MS and is related to cognitive performance as well. IIV is impaired in MS across the lifespan, including pediatric patients. IIV is a novel and sensitive marker of cognitive involvement in patients with MS, and may predict future cognitive decline as in other diseases

Cognitive impairment affects more than half of all individuals living with multiple sclerosis (MS). We hypothesized that training at home with an adaptive online cognitive training program would have greater cognitive benefit than ordinary computer games in cognitively-impaired adults with MS. This was a double-blind, randomized, active-placebo-controlled trial. Participants with MS were recruited through Stony Brook Medicine and randomly assigned to either the adaptive cognitive remediation (ACR) program or active control of ordinary computer games for 60 hours over 12 weeks. Training was remotely-supervised and delivered through a study-provided laptop computer. A computer generated, blocked stratification table prepared by statistician provided the randomization schedule and condition was assigned by a study technician. The primary outcome, administered by study psychometrician, was measured by change in a neuropsychological composite measure from baseline to study end. An intent-to-treat analysis was employed and missing primary outcome values were imputed via Markov Chain Monte Carlo method. Participants in the ACR (n = 74) vs. active control (n = 61) training program had significantly greater improvement in the primary outcome of cognitive functioning (mean change in composite z score+/-SD: 0.25+/-0.45 vs. 0.09+/-0.37, p = 0.03, estimated difference = 0.16 with 95% CI: 0.02-0.30), despite greater training time in the active control condition (mean+/-SD:56.9 +/- 34.6 vs. 37.7 +/-23 .8 hours played, p = 0.006). This study provides Class I evidence that adaptive, computer-based cognitive remediation accessed from home can improve cognitive functioning in MS. This telerehabilitation approach allowed for rapid recruitment and high compliance, and can be readily applied to other neurological conditions associated with cognitive dysfunction. TRIAL REGISTRATION: Clinicaltrials.gov NCT02141386.

BACKGROUND: Adverse childhood experiences (ACEs) exert a psychological and physiological toll that increases risk of chronic conditions, poorer social functioning, and cognitive impairment in adulthood. OBJECTIVE: To investigate the relationship between childhood adversity and clinical disease features in multiple sclerosis (MS). METHODS: Sixty-seven participants with MS completed the ACE assessment and neuropsychological assessments as part of a larger clinical trial of cognitive remediation. RESULTS: Adverse childhood experience scores, a measure of exposure to adverse events in childhood, significantly predicted age of MS onset (r = -0.30, p = 0.04). ACEs were also linked to reading recognition (a proxy for premorbid IQ) (r = -0.25, p = 0.04). ACE scores were not related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT). CONCLUSION: Childhood adversity may increase the likelihood of earlier age of onset and poorer estimated premorbid IQ in MS.

OBJECTIVES: Transcranial direct current stimulation (tDCS) has potential clinical application for symptomatic management in multiple sclerosis (MS). Repeated sessions are necessary in order to adequately evaluate a therapeutic effect. However, it is not feasible for many individuals with MS to visit clinic for treatment on a daily basis, and clinic delivery is also associated with substantial cost. We developed a research protocol to remotely supervise self- or proxy-administration for home delivery of tDCS using specially designed equipment and a telemedicine platform. MATERIALS AND METHODS: We targeted ten treatment sessions across two weeks. Twenty participants (n = 20) diagnosed with MS (any subtype), ages 30 to 69 years with a range of disability (Expanded Disability Status Scale or EDSS scores of 1.0 to 8.0) were enrolled to test the feasibility of the remotely supervised protocol. RESULTS: Protocol adherence exceeded what has been observed in studies with clinic-based treatment delivery, with all but one participant (95%) completing at least eight of the ten sessions. Across a total of 192 supervised treatment sessions, no session required discontinuation and no adverse events were reported. The most common side effects were itching/tingling at the electrode site. CONCLUSIONS: This remotely supervised tDCS protocol provides a method for safe and reliable delivery of tDCS for clinical studies in MS and expands patient access to tDCS.

Supporting young people with pediatric multiple sclerosis can be challenging for families and health care providers. Adolescents may be more resilient than adults in reaction to the diagnosis but can have more difficulty planning for their futures. Appropriate, sensitive, and focused health provision should include consideration of the perspective of both the patient and parents. Multidisciplinary management strategies are often effective, as are referrals to programs that enhance individual and family coping and strengthen a sense of community.

In comparison with the large body of evidence on cognitive functioning in adults with multiple sclerosis (MS), there is limited information on cognition in pediatric-onset MS (POMS). Unique vulnerabilities in POMS can derive from having a disease that occurs during key periods of age-expected brain growth, active myelination in the CNS, and maturation of neural networks during the learning curve and key formative years in the academic career of the patient. Therefore, the consequences of MS on developing cognitive faculties can be assessed only in the pediatric population and cannot be simply extrapolated from studies carried on in the adult population. Until the last decade, research in the pediatric population was mainly represented by small clinical series, often limited by the narrow scope of neuropsychological assessment and lack of adequate control groups. Over the last decade, however, cognitive functioning and mood-related difficulties have become an increasing concern as awareness of this population has grown. A few specialized MS centers have begun performing more systematic research in the field in order to assess the prevalence of cognitive impairments and mood-related difficulties in patients with POMS, to better characterize the neuropsychological pattern and determine the functional consequences of these problems. This chapter summarizes our current understanding of cognitive and mood-related difficulties in POMS and highlights perceived gaps in knowledge and priorities for future research.