Faculty Bibliography

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)

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

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.

OBJECTIVE: The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a self-report instrument, previously shown to differentiate patients with epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES). At present, the odds of MMPI-2-RF scale elevations in PNES patients, as well as the diagnostic predictive value of such scale elevations, remain largely unexplored. This can be of clinical utility, particularly when a diagnosis is uncertain. METHOD: After looking at mean group differences, we applied contingency table derived odds ratios to a sample of ES (n=92) and PNES (n=77) patients from a video EEG (vEEG) monitoring unit. We also looked at the positive and negative predictive values (PPV, NPV), as well as the false discovery rate (FDR) and false omission rate (FOR) for scales found to have increased odds of elevation in PNES patients. This was completed for the overall sample, as well as the sample stratified by sex. RESULTS: The odds of elevations related to somatic concerns, negative mood, and suicidal ideation in the PNES sample ranged from 2 to 5 times more likely. Female PNES patients had 3-6 times greater odds of such scale elevations, while male PNES patients had odds of 5-15 times more likely. PPV rates ranged from 53.66% to 84.62%, while NPV rates ranged from 47.52% to 90.91%. FDR across scales ranged from 15.38% to 50%, while the FOR ranged from 9.09% to 52.47%. CONCLUSIONS: Consistent with prior research, PNES patients have greater odds of MMPI-2-RF scale elevations, particularly related to somatic concerns and mood disturbance. Female PNES patients endorsed greater emotional distress, including endorsement of suicide related items. Elevations of these scales could aid in differentiating PNES from ES patients, although caution is warranted due to the possibility of both false positives and the incorrect omissions of PNES cases.

BACKGROUND: Given that post-traumatic headache is one of the most prevalent and long-lasting post-concussion sequelae, causes significant morbidity, and might be associated with slower neurocognitive recovery, we sought to evaluate the use of concussion screening scores in a concussion clinic population to assess for post-traumatic headache. METHODS: This is a retrospective cross-sectional study of 254 concussion patients from the New York University (NYU) Concussion Registry. Data on the headache characteristics, concussion mechanism, concussion screening scores were collected and analyzed. RESULTS: 72% of the patients had post-traumatic headache. About half (56.3%) were women. The mean age was 35 (SD 16.2). 90 (35%) patients suffered from sport-related concussions (SRC). Daily post-traumatic headache patients had higher Sport Concussion Assessment Tool (SCAT)-3 symptom severity scores than the non-daily post-traumatic headache and the headache-free patients (50.2 [SD 28.2] vs. 33.1 [SD 27.5] vs. 21.6 SD23], p < 0.001). Patients with SRC had lower headache intensity (4.47 [SD 2.5] vs. 6.24 [SD 2.28], p < 0.001) and SCAT symptom severity scores (33.9 [SD 27.4] vs. 51.4 [SD 27.7], p < 0.001) than the other patients, but there were no differences in post-traumatic headache prevalence, frequency, and Standardized Assessment of Concussion (SAC) scores. CONCLUSION: The presence and frequency of post-traumatic headache are associated with the SCAT-3 symptom severity score, which is the most important predictor for post-concussion recovery. The SCAT-3 symptom severity score might be a useful tool to help characterize patients' post-traumatic headache.

Neuropsychologists regularly conduct sport-related concussion (SRC) evaluations, although research has not tracked these assessment practices. As part of a survey of neuropsychological test usage, we analyzed data from 215 neuropsychologists who conduct SRC evaluations. Only 15% reported conducting baseline assessments of athletes as part of a sports program and 92% evaluate athletes' post-concussion without baseline data. The majority of respondents use a full battery, considered the most reliable approach for assessing concussion symptoms in athletes. Only 6% use computerized tests exclusively (>50% ImPACT). We discuss the implications of these results and address challenges faced by neuropsychologists who perform SRC evaluations.

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.

OBJECTIVES: The aim of this study was to evaluate the reliability and validity of three computerized neurocognitive assessment tools (CNTs; i.e., ANAM, DANA, and ImPACT) for assessing mild traumatic brain injury (mTBI) in patients recruited through a level I trauma center emergency department (ED). METHODS: mTBI (n=94) and matched trauma control (n=80) subjects recruited from a level I trauma center emergency department completed symptom and neurocognitive assessments within 72 hr of injury and at 15 and 45 days post-injury. Concussion symptoms were also assessed via phone at 8 days post-injury. RESULTS: CNTs did not differentiate between groups at any time point (e.g., M 72-hr Cohen's d=-.16, .02, and .00 for ANAM, DANA, and ImPACT, respectively; negative values reflect greater impairment in the mTBI group). Roughly a quarter of stability coefficients were over .70 across measures and test-retest intervals in controls. In contrast, concussion symptom score differentiated mTBI vs. control groups acutely), with this effect size diminished over time (72-hr and day 8, 15, and 45 Cohen's d=-.78, -.60, -.49, and -.35, respectively). CONCLUSIONS: The CNTs evaluated, developed and widely used to assess sport-related concussion, did not yield significant differences between patients with mTBI versus other injuries. Symptom scores better differentiated groups than CNTs, with effect sizes weaker than those reported in sport-related concussion studies. Nonspecific injury factors, and other characteristics common in ED settings, likely affect CNT performance across trauma patients as a whole and thereby diminish the validity of CNTs for assessing mTBI in this patient population. (JINS, 2017, 23, 293-303).

The differential contribution of medial-temporal lobe regions to verbal declarative memory is debated within the neuroscience, neuropsychology, and cognitive psychology communities. We evaluate whether the extent of surgical resection within medial-temporal regions predicts longitudinal verbal learning and memory outcomes. This single-center retrospective observational study involved patients with refractory temporal lobe epilepsy undergoing unilateral anterior temporal lobe resection from 2007 to 2015. Thirty-two participants with Engel Classes 1 and 2 outcomes were included (14 left, 18 right) and followed for a mean of 2.3 years after surgery (+/-1.5 years). Participants had baseline and postsurgical neuropsychological testing and high-resolution T1-weighted MRI scans. Postsurgical lesions were manually traced and coregistered to presurgical scans to precisely quantify resection extent of medial-temporal regions. Verbal learning and memory change scores were regressed on hippocampal, entorhinal, and parahippocampal resection volume after accounting for baseline performance. Overall, there were no significant differences in learning and memory change between patients who received left and right anterior temporal lobe resection. After controlling for baseline performance, the extent of left parahippocampal resection accounted for 27% (p = .021) of the variance in verbal short delay free recall. The extent of left entorhinal resection accounted for 37% (p = .004) of the variance in verbal short delay free recall. Our findings highlight the critical role that the left parahippocampal and entorhinal regions play in recall for verbal material.