Faculty Bibliography

BACKGROUND:Spinocerebellar ataxia type 27 B (SCA27B) caused by GAA trinucleotide repeats in the fibroblast growth factor 14 gene is emerging as a common cause of late-onset ataxia. Oscillopsia due to downbeat nystagmus (DBN) and diplopia are common symptoms, yet the causes of diplopia and strabismus patterns are poorly defined. METHODS:Retrospective chart review of 18 patients diagnosed with SCA27B over the past year. RESULTS:Ten of 18 patients had episodic or persistent oscillopsia or diplopia at disease onset, neurologically isolated in 4. Seventeen had detectable DBN, although it was often delayed in onset and was clinically obvious in only 5. Diplopia was present in 14 patients: vertical due to skew deviation (static and or alternating on lateral gaze) (n = 8) and/or horizontal due to vergence dysfunction (n = 11). Symptomatic vergence dysfunction included convergence insufficiency (CI) (n = 4) and divergence insufficiency (n = 5). Thirteen of 16 patients experienced improvement in oscillopsia or imbalance on 4-aminopyridine (4-AP). CONCLUSIONS:Strabismus patterns causing diplopia in patients with SCA27B are, not unexpectedly, largely attributable to cerebellar dysfunction and are not unique to SCA27B. The exceptions to cerebellar localization were CI, sixth nerve palsy, and slow saccades. Careful assessment for DBN in patients presenting with episodic or persistent diplopia from skew deviation or vergence disorders is important, as this may be key to confirming a cerebellar localization, subtle on examination, and guide toward genetic testing and 4-AP treatment.

BACKGROUND:The RESCUE-ICAS study (Registry of Emergent Large-Vessel Occlusion due to Intracranial Stenosis) demonstrated that patients undergoing acute stenting of intracranial atherosclerosis with large-vessel occlusion after mechanical thrombectomy had better outcomes than those undergoing mechanical thrombectomy alone. We present 2 secondary analyses of RESCUE-ICAS to evaluate intracranial stenting among patients who achieved successful reperfusion. METHODS:From a prospective observational cohort of 25 stroke centers (2022-2023), patients with acute intracranial occlusion, National Institutes of Health Stroke Scale score ≥6, and 50% to 99% residual stenosis or occlusion after endovascular thrombectomy were included. In the first analysis, we compared patients with stenting versus those without stenting from among those patients with a final modified Thrombolysis in Cerebral Infarction score of 2B-3. In the second analysis, we compared patients who underwent stenting with those who did not from among the patients with a Thrombolysis in Cerebral Infarction (TICI) score of 2B-3 before stenting. The odds of a favorable 90-day mRS (0-2) and 24-hour MRI infarct volume <30 mL were assessed using multivariable logistic regression. We also examined the rates of symptomatic ICH and death at 90 days in these cohorts. RESULTS:=0.480). CONCLUSIONS:Among both the cohort with final successful reperfusion and the cohort with initial successful reperfusion after mechanical thrombectomy alone, intracranial stenting was associated with better long-term clinical and radiographic outcomes, without higher morbidity and mortality. REGISTRATION/BACKGROUND:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05403593.

Positive airway pressure (PAP) adherence is lower in African Americans (AAs) and, possibly, Hispanics as compared to Whites. Access to other treatment modalities is also limited in these groups. In children, obstructive sleep apnea (OSA) prevalence is higher among AAs, Hispanics, and Asian Americans. AA children have lower rates of adenotonsillectomy. Interventions to dissipate misconceptions about sleep and OSA, better patient-provider communication, and standardized and targeted surveys and procedures are necessary to minimize this problem. This section will review disparities in PAP treatment and other options, as well as children's phenotypes, associated factors, and potential interventions.

Obstructive Sleep Apnea (OSA) is an extremely prevalent disorder and mostly underdiagnosed. Its prevalence is even higher among African Americans (AA), Hispanic, Asian Americans and Native Americans (NA) adults and children. AA present younger, with more severe and comorbid OSA, and are sleepier than their white counterparts. Evidence suggests this problem could be as severe in Hispanics, Asian Americans and NA. This first part of the review will focus on epidemiology and data in the adult population.

INTRODUCTION/BACKGROUND:Though brain fog is common in Long-coronavirus disease 2019 (Long-COVID), the incidence of mild cognitive impairment (MCI) is unknown. METHODS:In an observational cohort study, recovered COVID-positive, Long-COVID, and COVID-negative subjects underwent blinded evaluation using National Alzheimer's Coordinating Center (NACC) and National Institute on Aging (NIA) -Alzheimer's Association diagnostic criteria for dementia and MCI. The cumulative incidence of MCI was calculated for each group, and the hazard of MCI was compared between groups. RESULTS:Among 260 subjects, the cumulative incidence of MCI over 4.4 years was higher with Long-COVID (27%) versus recovered-COVID (5%) or COVID-negative status (1%). There was a higher hazard of MCI for patients with Long-COVID compared to those without (hazard ratio [HR] 3.93, 95% confidence interval [CI] 1.86-8.31, p < 0.001), and specifically for the Alzheimer's disease (AD) -related MCI subtype (HR 3.20, 95% confidence interval [CI] 1.14-9.00, p = 0.027). DISCUSSION/CONCLUSIONS:The cumulative incidence and adjusted hazard of MCI (and specifically AD-related MCI) at 4.4 years was significantly higher among Long-COVID patients compared to recovered-COVID and COVID-negative controls.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Double seronegative NMOSD (DS-NMOSD) lacks approved disease-modifying treatments, and limited data exist on optimal relapse-prevention strategies. In this multicenter, international, retrospective cohort study, we sought to compare the real-world effectiveness of anti-CD20 agents vs nonspecific immunosuppressants as disease-modifying strategies for relapse prevention in DS-NMOSD. METHODS:A retrospective cohort database was constructed using standardized data collection from medical records across collaborating centers in the United States, Brazil, the United Kingdom, Thailand, Turkiye, and China. Patients meeting IPND-2015 NMOSD criteria with negative serum aquaporin-4 and myelin oligodendrocyte glycoprotein antibody testing via cell-based assays and at least 12 months of follow-up were reviewed. The primary outcome was the incidence rate ratio (IRR) of relapses; secondary outcomes included the annualized relapse rate (ARR) and time to relapse. RESULTS:A total of 103 patients with DS-NMOSD met study criteria, with a median follow-up of 6 years. Anti-CD20 therapy was associated with a significantly lower IRR (0.02, 95% CI 0.01-0.04) and ARR (0.17, 95% CI 0.07-0.40) compared with nonspecific immunosuppressants (0.76, 95% CI 0.40-1.43) after adjusting for covariates. Survival analysis demonstrated a prolonged relapse-free interval with anti-CD20 agents. DISCUSSION/CONCLUSIONS:Our findings support the use of B-cell depletion as a potentially superior relapse-prevention strategy in DS-NMOSD, highlighting its potential as a first-line therapy. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class IV evidence that, in patients with DS-NMOSD, treatment with a DMT reduces relapse incidence rate ratio compared with no treatment and anti-CD20 DMTs are associated with a lower relapse incidence rate ratio compared with nonspecific immunosuppressants.

BACKGROUND:Efforts to assess concussion-reporting efficacy face logistical challenges relying on behavioral intentions. Self-report surveys often lack correlation with actual behavior. Simulated in-game behavioral observation may offer a better evaluation method when data on actual behavior are not feasibly collected. OBJECTIVE:To examine the association between concussion-reporting intentions and concussion-reporting behavior in a novel simulated in-game experience. DESIGN/METHODS:This study was performed as a secondary analysis of a larger study that assessed the efficacy of concussion education in concussion-reporting intention among high school athletes. High school football players (n = 313) from seven Colorado high schools completed reporting intention questionnaires. Athletes were randomized to either receive standard concussion education from the Centers for Disease Control and Prevention (n = 167) or not (n = 146). Subsequently, all participants were given a baseline assessment in which they were asked to assess concussion-reporting intention. To test concussion-reporting behavior, all participants watched a novel first-person, 2-minute video in which a simulated concussion occurred. When the simulated concussion occurs, participants are then asked whether they would like to seek evaluation or continue playing. Logistic regression assessed the relationship between concussion-reporting intention and concussion-reporting behavior during the simulated game experience. RESULTS:Athletes who reported their concussion in the simulated game had higher baseline concussion-reporting intention (U = 8669.5, p < .001). Across both the educated and noneducated groups, each one-point increase in baseline reporting intention was associated with 1.99× (95% confidence interval [CI]: 1.11-3.60, p = .02) and 1.53× (95% CI: 1.07-2.30, p = .026) increased odds of reporting the simulated concussion, respectively. CONCLUSIONS:Concussion-reporting behavior in a novel, first-person simulated in-game experience is higher among individuals with higher baseline concussion-reporting intention. This approach may offer promise for evaluating concussion-reporting intention and concussion-reporting behavior via interactive video simulation.

INTRODUCTION/BACKGROUND:We examined obstructive sleep apnea (OSA) severity's association with Alzheimer's disease (AD) plasma biomarkers, independent or synergistic with cerebrospinal fluid (CSF) amyloid, and as a proof of concept, whether plasma amyloid beta (Aβ)42/Aβ40 with OSA severity improves detection of amyloidosis and tau pathology. METHODS:In 120 cognitively normal older adults (70 with CSF data) from New York University sleep and aging studies (2013-2021), OSA severity was measured using apnea/hypopnea index with 4% desaturation; plasma Aβ40, Aβ42, tau, and neurofilament light chain (NfL) via single molecule array; CSF amyloid and tau via enzyme-linked immunosorbent assay. Associations evaluated adjusted correlations and generalized models; receiver operating characteristic analyses evaluated diagnostic accuracy. RESULTS:OSA severity correlated with plasma Aβ40 (r = 0.21), Aβ42 (r = 0.26), and Aβ42/Aβ40 (r = 0.20). Plasma tau and NfL associations depended on CSF-Aβ42. OSA severity with Aβ42/Aβ40 improved CSF amyloidosis (area under the curve [AUC] = 0.78) and tau pathology (AUC = 0.71) detection. DISCUSSION/CONCLUSIONS:OSA severity relates to elevated plasma Aβ and, with CSF amyloid, to tau/NfL. Combined plasma and OSA measures aid non-invasive AD associations' detection.