Faculty Bibliography

OBJECTIVE:This study was undertaken to conduct external validation of previously published epilepsy surgery prediction tools using a large independent multicenter dataset and to assess whether these tools can stratify patients for being operated on and for becoming free of disabling seizures (International League Against Epilepsy stage 1 and 2). METHODS:We analyzed a dataset of 1562 patients, not used for tool development. We applied two scales: Epilepsy Surgery Grading Scale (ESGS) and Seizure Freedom Score (SFS); and two versions of Epilepsy Surgery Nomogram (ESN): the original version and the modified version, which included electroencephalographic data. For the ESNs, we used calibration curves and concordance indexes. We stratified the patients into three tiers for assessing the chances of attaining freedom from disabling seizures after surgery: high (ESGS = 1, SFS = 3-4, ESNs > 70%), moderate (ESGS = 2, SFS = 2, ESNs = 40%-70%), and low (ESGS = 2, SFS = 0-1, ESNs < 40%). We compared the three tiers as stratified by these tools, concerning the proportion of patients who were operated on, and for the proportion of patients who became free of disabling seizures. RESULTS:The concordance indexes for the various versions of the nomograms were between .56 and .69. Both scales (ESGS, SFS) and nomograms accurately stratified the patients for becoming free of disabling seizures, with significant differences among the three tiers (p < .05). In addition, ESGS and the modified ESN accurately stratified the patients for having been offered surgery, with significant difference among the three tiers (p < .05). SIGNIFICANCE/CONCLUSIONS:ESGS and the modified ESN (at thresholds of 40% and 70%) stratify patients undergoing presurgical evaluation into three tiers, with high, moderate, and low chance for favorable outcome, with significant differences between the groups concerning having surgery and becoming free of disabling seizures. Stratifying patients for epilepsy surgery has the potential to help select the optimal candidates in underprivileged areas and better allocate resources in developed countries.

OBJECTIVE:To examine the usefulness of carotid web (CW), carotid bifurcation and their combined angioarchitectural measurements in assessing stroke risk. METHODS:Anatomic data on the internal carotid artery (ICA), common carotid artery (CCA), and the CW were gathered as part of a retrospective study from symptomatic (stroke) and asymptomatic (nonstroke) patients with CW. We built a model of stroke risk using principal-component analysis, Firth regression trained with 5-fold cross-validation, and heuristic binary cutoffs based on the Minimal Description Length principle. RESULTS:The study included 22 patients, with a mean age of 55.9 ± 12.8 years; 72.9% were female. Eleven patients experienced an ischemic stroke. The first 2 principal components distinguished between patients with stroke and patients without stroke. The model showed that ICA-pouch tip angle (P = 0.036), CCA-pouch tip angle (P = 0.036), ICA web-pouch angle (P = 0.036), and CCA web-pouch angle (P = 0.036) are the most important features associated with stroke risk. Conversely, CCA and ICA anatomy (diameter and angle) were not found to be risk factors. CONCLUSIONS:This pilot study shows that using data from computed tomography angiography, carotid bifurcation, and CW angioarchitecture may be used to assess stroke risk, allowing physicians to tailor care for each patient according to risk stratification.

PURPOSE/OBJECTIVE:Validated measures capable of demonstrating meaningful interventional change in the CDKL5 deficiency disorder (CDD) are lacking. The study objective was to modify the Rett Syndrome Gross Motor Scale (RSGMS) and evaluate its psychometric properties for individuals with CDD. METHODS:Item and scoring categories of the RSGMS were modified. Caregivers registered with the International CDKL5 Clinical Research Network uploaded motor videos filmed at home to a protected server and completed a feedback questionnaire (n = 70). Rasch (n = 137), known groups (n = 109), and intra- and inter-rater reliability analyses (n = 50) were conducted. RESULTS:The age of individuals with CDD ranged from 1.5 to 34.1 years. The modified scale, Gross Motor-Complex Disability (GM-CD), comprised 17 items. There were no floor or ceiling effects and inter- and intra-rater reliability were good. Rasch analysis demonstrated that the items encompassed a large range of performance difficulty, although there was some item redundancy and some disordered categories. One item, Prone Head Position, was a poor fit. Caregiver-reported acceptability was positive. Scores differed by age and functional abilities. SUMMARY/CONCLUSIONS:GM-CD appears to be a suitable remotely administered measure and psychometrically sound for individuals with CDD. This study provides the foundation to propose the use of GM-CD in CDD clinical trials. Longitudinal evaluation is planned.

INTRODUCTION/BACKGROUND:Alzheimer's disease (AD) and primary age-related tauopathy (PART) both harbor 3R/4R hyperphosphorylated-tau (p-tau)-positive neurofibrillary tangles (NFTs) but differ in the spatial p-tau development in the hippocampus. METHODS:Using Nanostring GeoMx Digital Spatial Profiling, we compared protein expression within hippocampal subregions in NFT-bearing and non-NFT-bearing neurons in AD (n = 7) and PART (n = 7) subjects. RESULTS:Proteomic measures of synaptic health were inversely correlated with the subregional p-tau burden in AD and PART, and there were numerous differences in proteins involved in proteostasis, amyloid beta (Aβ) processing, inflammation, microglia, oxidative stress, and neuronal/synaptic health between AD and PART and between definite PART and possible PART. DISCUSSION/CONCLUSIONS:These results suggest subfield-specific proteome differences that may explain some of the differences in Aβ and p-tau distribution and apparent pathogenicity. In addition, hippocampal neurons in possible PART may have more in common with AD than with definite PART, highlighting the importance of Aβ in the pathologic process. HIGHLIGHTS/CONCLUSIONS:Synaptic health is inversely correlated with local p-tau burden. The proteome of NFT- and non-NFT-bearing neurons is influenced by the presence of Aβ in the hippocampus. Neurons in possible PART cases share more proteomic similarities with neurons in ADNC than they do with neurons in definite PART cases.

Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes. A wide range of evidence suggests that ultra-early bundled care, with multiple simultaneous interventions in the acute phase, offers the best hope of limiting hematoma expansion and improving functional recovery. Patients with intracerebral hemorrhage who fail to receive early aggressive care have worse outcomes, suggesting that an important treatment opportunity exists. This consensus statement puts forth a call to action to establish a protocol for Code ICH, similar to current strategies used for the management of acute ischemic stroke, through which early intervention, bundled care, and time-based metrics have substantially improved neurological outcomes. Based on current evidence, we advocate for the widespread adoption of an early bundle of care for patients with intracerebral hemorrhage focused on time-based metrics for blood pressure control and emergency reversal of anticoagulation, with the goal of optimizing the benefit of these already widely used interventions. We hope Code ICH will endure as a structural platform for continued innovation, standardization of best practices, and ongoing quality improvement for years to come.

B-cell depleting therapies are effective in multiple sclerosis (MS) and are widely used (Hauser et al., 2017). Inflammatory vaginitis (IV), characterized by unexplained vaginal symptoms including mucopurulent discharge, pain, irritation, and dyspareunia, has been reported in one MS patient on ocrelizumab (Filikci and Jensen, 2022), and to be present in 3.5 % of women on rituximab for autoimmune diseases (Yockey et al., 2021). We report here four cases of IV in B cell depleted women with MS. B-cell reconstitution was temporally associated with improvement of IV symptoms. Further investigation and vigilance for this potential treatment emergent adverse event affecting sexual and reproductive health of women with MS is needed.

BACKGROUND:Although racial and ethnic differences in CPAP adherence for OSA are widely established, no studies have examined the influence of perceived racial discrimination on CPAP usage, to our knowledge. RESEARCH QUESTION/OBJECTIVE:(1) Do Black adults with OSA report experiencing greater amounts of discrimination than non-Hispanic White adults? (2) Is discrimination associated with poorer CPAP adherence over time, independent of self-identified race? (3) Does discrimination mediate the relationship between self-identified Black race and CPAP usage? STUDY DESIGN AND METHODS/METHODS:/Fisher exact test, as appropriate. A linear regression model was completed with self-identified Black race and EDS total score as the primary independent variables of interest and mean daily CPAP usage at 30 and 90 days serving as the dependent outcomes. This regression modeling was repeated after adjusting for psychosocial variables known to be associated with CPAP usage. EDS total score was explored as a potential mediator of the association between self-identified Black race and mean daily CPAP adherence at 30 and 90 days. RESULTS:The sample for this analysis consisted of 78 participants (31% female, 38% Black) with a mean age of 57 ± 14 years. Sixty percent of the Black adults reported they experienced racial discrimination at least a few times each year. Relative to White adults, Black adults were also more likely to indicate more than one reason for discrimination (27% vs 4%, P = .003). Adjusting for discrimination, self-identified Black race was associated with 1.4 (95% CI, -2.3 to -0.4 h; P = .006) and 1.6 (95% CI, -2.6 to -0.6 h; P = .003) fewer hours of mean daily CPAP usage at 30 and 90 days, respectively. In the fully adjusted model, a 1-unit change in the total discrimination score (more discrimination) was associated with a 0.08-h (95% CI, 0.01-0.15 h; P = .029) and 0.08-h (95% CI, 0.01-0.16 h; P = .045) change in mean daily CPAP usage at 30 and 90 days, respectively. INTERPRETATION/CONCLUSIONS:Adults with OSA who encountered racial discrimination experienced greater decrement in CPAP usage than those who did not experience racial discrimination.

BACKGROUND:The impact of disease-modifying treatments (DMTs) on multiple sclerosis (MS) long-term outcomes is continuously evolving. Retrospective analyses of large and long-term registries could provide information regarding general disease trajectories and risk factors that are commonly not investigated in shorter clinical trial settings. METHODS:Retrospective observational study of people with MS (pwMS) registered in New York State MS Consortium (NYSMSC) since 1996. Disability outcomes of reaching sustained Expanded Disability Status Scale (EDSS) scores of 4.0, 6.0 and transition to secondary-progressive MS (SPMS) were confirmed at follow-up. Four DMT categories were determined (1) continuous DMT use, (2) discontinued DMT, (3) (re)started DMT and (4) never treated with DMT. Patient-reported outcomes (PRO) were acquired using LIFEware system. Kaplan-Meier survival curves and adjusted analysis of covariance (ANCOVA) were used to determine the rate and factors related to disability progression. RESULTS:Total of 1893 pwMS were included with baseline average age of 43.2 years (SD = 10.4), 9.6 years of disease duration (SD = 8.8), median EDSS of 3.0 (IQR 2.0-3.5) and average follow-up time of 6.9 years (SD = 4.9). In addition to being male, older, more disabled and reporting worse PROs at baseline, pwMS who discontinued DMT had more than 5.5 times greater risk of reaching sustained EDSS of 4.0 (OR = 5.56, 95% CI 2.78-11.0, p < 0.001). Similarly, pwMS who discontinued DMT during the NYSMSC follow-up had 3.8- and 4.7-times greater risk to reach sustained EDSS 6.0 (OR = 3.86, 95% CI 2.12-7.02, p < 0.001), and to transition to SPMS (OR = 4.77, 95% CI 2.9-7.87, p < 0.001). Propensity matching analysis confirmed the worse clinical outcomes. CONCLUSIONS:In addition to known predictors of long-term clinical outcomes, pwMS who discontinue DMT have worse long-term disability trajectory when compared to both early and late DMT starters. PRO-based indicators may suggest worse clinical outcomes.

Understanding the structural and functional neuroanatomy of core consciousness (ie, wakefulness and awareness) is an asset to clinicians caring for persons with disorders of consciousness. This article provides a primer on the structural and functional neuroanatomy of wakefulness and awareness. The neuroanatomical structures supporting these elements of core consciousness functions are reviewed first, after which brief description of the clinically evaluable relationships between disruption of these structures and disorders of consciousness (ie, brain-behavior relationships) are outlined. Consideration of neuroanatomy at the mesoscale (ie, the mesocircuit hypothesis) as well as in relation to several large-scale neural networks is offered.

BACKGROUND:The relationship between perceived social support and continuous positive airway pressure remains understudied among individuals with obstructive sleep apnea. The aim of this prospective cohort study was to determine if baseline perceived social support and subtypes predict regular continuous positive airway pressure use after 1month of therapy. METHODS:Adults with obstructive sleep apnea initiating continuous positive airway pressure therapy were recruited from sleep clinics in New York City. Demographics, medical history, and comorbidities were obtained from patient interview and review of medical records. Objective continuous positive airway pressure adherence data was collected at the first clinical follow-up. RESULTS:Seventy-five participants (32% female; non-Hispanic Black 41%; mean age of 56 ± 14years) provided data. In adjusted analyses, poorer levels of overall social support, and subtypes including informational/emotional support, and positive social interactions were associated with lower continuous positive airway pressure use at 1month. Relative to patients reporting higher levels of support, participants endorsing lower levels of overall social support, positive social interaction and emotional/informational support had 1.6 hours (95% CI: 0.5,2.7, hours; p = .007), 1.3 hours (95% CI: 0.2,2.4; p = .026), and 1.2 hours (95% CI: 0.05,2.4; p = .041) lower mean daily continuous positive airway pressure use at 1month, respectively. CONCLUSION/CONCLUSIONS:Focusing on social support overall and positive social interaction particularly, could be an effective approach to improve continuous positive airway pressure adherence in patients at risk of suboptimal adherence.