Faculty Bibliography

OBJECTIVE:To report outcomes on patients with multiple sclerosis (MS) and related disorders with coronavirus disease 2019 (COVID-19) illness. METHODS:From March 16 to April 30, 2020, patients with MS or related disorders at NYU Langone MS Comprehensive Care Center were identified with laboratory-confirmed or suspected COVID-19. The diagnosis was established using a standardized questionnaire or by review of in-patient hospital records. RESULTS:We identified 76 patients (55 with relapsing MS, of which 9 had pediatric onset; 17 with progressive MS; and 4 with related disorders). Thirty-seven underwent PCR testing and were confirmed positive. Of the entire group, 64 (84%) patients were on disease-modifying therapy (DMT) including anti-CD20 therapies (n = 34, 44.7%) and sphingosine-1-phosphate receptor modulators (n = 10, 13.5%). The most common COVID-19 symptoms were fever and cough, but 21.1% of patients had neurologic symptom recrudescence preceding or coinciding with the infection. A total of 18 (23.7%) were hospitalized; 8 (10.5%) had COVID-19 critical illness or related death. Features more common among those hospitalized or with critical illness or death were older age, presence of comorbidities, progressive disease, and a nonambulatory status. No DMT class was associated with an increased risk of hospitalization or fatal outcome. CONCLUSIONS:Most patients with MS with COVID-19 do not require hospitalization despite being on DMTs. Factors associated with critical illness were similar to the general at-risk patient population. DMT use did not emerge as a predictor of poor COVID-19 outcome in this preliminary sample.

BACKGROUND:The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE:To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS:The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research - with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS:A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION/CONCLUSIONS:There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.

Walking impairments are a debilitating feature of multiple sclerosis (MS) because of the direct interference with daily activity. The management of motor symptoms in those with MS remains a therapeutic challenge. Transcranial direct current stimulation (tDCS) is a type of non-invasive brain stimulation that is emerging as a promising rehabilitative tool but requires further characterization to determine its optimal therapeutic use. In this randomized, sham-controlled proof-of-concept study, we tested the immediate effects of a single tDCS session on walking and functional mobility in those with MS. Seventeen participants with MS completed one 20-min session of aerobic exercise, randomly assigned to be paired with either active (2.5 mA, n = 9) or sham (n = 8) tDCS over the primary motor cortex (M1). The groups (active vs. sham) were matched according to gender (50% vs. 60% F), age (52.1 ± 12.85 vs. 54.2 ± 8.5 years), and level of neurological disability (median Expanded Disability Status Scale score 5.5 vs. 5). Gait speed on the 10-m walk test and the Timed Up and Go (TUG) time were measured by a wearable inertial sensor immediately before and following the 20-min session, with changes compared between conditions and time. There were no significant differences in gait speed or TUG time changes following the session in the full sample or between the active vs. sham groups. These findings suggest that a single session of anodal tDCS over M1 is not sufficient to affect walking and functional mobility in those with MS. Instead, behavioral motor response of tDCS is likely to be cumulative, and the effects of multiple tDCS sessions require further study. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03658668.

OBJECTIVE:To identify cognitive phenotypes in temporal lobe epilepsy (TLE) and test their reproducibility in a large, multi-site cohort of patients using both data-driven and clinically driven approaches. METHOD/METHODS:Four-hundred seven patients with TLE who underwent a comprehensive neuropsychological evaluation at one of four epilepsy centers were included. Scores on tests of verbal memory, naming, fluency, executive function, and psychomotor speed were converted into z-scores based on 151 healthy controls (HCs). For the data-driven method, cluster analysis (k-means) was used to determine the optimal number of clusters. For the clinically driven method, impairment was defined as >1.5 standard deviations below the mean of the HC, and patients were classified into groups based on the pattern of impairment. RESULTS:Cluster analysis revealed a three-cluster solution characterized by (a) generalized impairment (29%), (b) language and memory impairment (28%), and (c) no impairment (43%). Based on the clinical criteria, the same broad categories were identified, but with a different distribution: (a) generalized impairment (37%), (b) language and memory impairment (30%), and (c) no impairment (33%). There was a 82.6% concordance rate with good agreement (κ = .716) between the methods. Forty-eight patients classified as having a normal profile based on cluster analysis were classified as having generalized impairment (n = 16) or an isolated language/memory impairment (n = 32) based on the clinical criteria. Patients with generalized impairment had a longer disease duration and patients with no impairment had more years of education. However, patients demonstrating the classic TLE profile (ie, language and memory impairment) were not more likely to have an earlier age at onset or mesial temporal sclerosis. SIGNIFICANCE/CONCLUSIONS:We validate previous findings from single-site studies that have identified three unique cognitive phenotypes in TLE and offer a means of translating the patterns into a clinical diagnostic criteria, representing a novel taxonomy of neuropsychological status in TLE.

BACKGROUND AND PURPOSE/OBJECTIVE:Efficacy of restorative cognitive rehabilitation can be predicted from baseline patient factors. In addition, patient profiles of functional connectivity are associated with cognitive reserve and moderate the structure-cognition relationship in people with multiple sclerosis (PwMS). Such interactions may help predict which PwMS will benefit most from cognitive rehabilitation. Our objective was to determine whether patient response to restorative cognitive rehabilitation is predictable from baseline structural network disruption and whether this relationship is moderated by functional connectivity. METHODS:For this single-arm repeated measures study, we recruited 25 PwMS for a 12-week program. Following magnetic resonance imaging, participants were tested using the Symbol Digit Modalities Test (SDMT) pre- and postrehabilitation. Baseline patterns of structural and functional connectivity were characterized relative to healthy controls. RESULTS:= .385, P = .017, Interaction β = -.415). CONCLUSION/CONCLUSIONS:Patient response to restorative cognitive rehabilitation is predictable from the interaction between structural network disruption and functional connectivity in the default-mode network. This effect may be related to cognitive reserve.

Pediatric neuropsychologists are increasingly recognizing the importance of performance validity testing during evaluations. The use of such measures to detect insufficient effort is of particular importance in pediatric epilepsy evaluations, where test results are often used to guide surgical decisions and failure to detect poor task engagement can result in postsurgical cognitive decline. The present investigation assesses the utility of the Medical Symptom Validity Test (MSVT) in 104 clinically referred children and adolescents with epilepsy. Though the overall failure rate was 15.4% of the total group, children with 2nd grade or higher reading skills (a requirement of the task) passed at a very high rate (96.6%). Of the three failures, two were unequivocally deemed true positives, while the third failed due to extreme somnolence during testing. Notably, for those with ≥2nd grade reading levels, MSVT validity indices were unrelated to patient age, intellectual functioning, or age of epilepsy onset, while modest relations were seen with specific memory measures, number of epilepsy medications, and seizure frequency. Despite these associations, however, this did not result in more failures in this population of children and adolescents with substantial neurologic involvement, as pass rates exceeded 92% for those with intellectual disability, high seizure frequency, high medication burden, and even prior surgical resection of critical memory structures.

BACKGROUND:Transcranial direct current stimulation (tDCS) is a method of noninvasive neuromodulation and potential therapeutic tool to improve functioning and relieve symptoms across a range of central and peripheral nervous system conditions. Evidence suggests that the effects of tDCS are cumulative with consecutive daily applications needed to achieve clinically meaningful effects. Therefore, there is growing interest in delivering tDCS away from the clinic or research facility, usually at home. OBJECTIVE:To provide a comprehensive guide to operationalize safe and responsible use of tDCS in home settings for both investigative and clinical use. METHODS:Providing treatment at home can improve access and compliance by decreasing the burden of time and travel for patients and their caregivers, as well as to reach those in remote locations and/or living with more advanced disabilities. RESULTS:To date, methodological approaches for at-home tDCS delivery have varied. After implementing the first basic guidelines for at-home tDCS in clinical trials, this work describes a comprehensive guide for facilitating safe and responsible use of tDCS in home settings enabling access for repeated administration over time. CONCLUSION/CONCLUSIONS:These guidelines provide a reference and standard for practice when employing the use of tDCS outside of the clinic setting.