Faculty Bibliography

Digital health technologies (DHTs) can transform neurological assessments, improving quality and continuity of care. In the United States, the Food & Drug Administration (FDA) oversees the safety and efficacy of these technologies, employing a detailed regulatory process that classifies devices based on risk and requires rigorous review and post-market surveillance. Following FDA approval, DHTs enter the Current Procedural Terminology, Relative Value Scale Update Committee, and Centers for Medicare & Medicaid Services coding and valuation processes leading to coverage and payment decisions. DHT adoption is challenged by rapid technologic advancements, an inconsistent evidence base, marketing discrepancies, ambiguous coding guidance, and variable health insurance coverage. Regulators, policymakers, and payers will need to develop better methods to evaluate these promising technologies and guide their deployment. This includes striking a balance between patient safety and clinical effectiveness versus promotion of innovation, especially as DHTs increasingly incorporate artificial intelligence. Data validity, cybersecurity, risk management, societal, and ethical responsibilities should be addressed. Regulatory advances can support adoption of these promising tools by ensuring DHTs are safe, effective, accessible, and equitable.

OBJECTIVES/OBJECTIVE:Despite the potential importance of the neighborhood social environment for cognitive health, the connection between neighborhood characteristics and dementia remains unclear. This study investigated the association between the prospective risk of dementia and three distinct aspects of neighborhood social environment: socioeconomic deprivation, disorder, and social cohesion. We also examined whether objective and subjective aspects of individual-level social isolation may function as mediators. METHODS:Leveraging data from the Health and Retirement Study (2006-2018; N = 9,251), we used Cox proportional hazards models to examine the association between time-to-dementia incidence and each neighborhood characteristic, adjusting for covariates and the propensity to self-select into disadvantaged neighborhoods. We used inverse odds weighting to decompose significant total effects of neighborhood characteristics into mediational effects of objective and subjective social isolation. RESULTS:The risk of dementia was associated with deprivation and disorder but not low cohesion. In deprived neighborhoods, individuals had an 18% increased risk of developing dementia (cause-specific hazard ratio [CHR] = 1.18, 95% CI: 1.02 to 1.38), and those in disordered areas had a 27% higher risk (CHR = 1.27, 95% CI: 1.03 to 1.59). 20% of the disorder's effects were mediated by subjective social isolation, while the mediational effects of objective isolation were nonsignificant. Deprivation's total effects were not partitioned into mediational effects given its nonsignificant associations with the mediators. DISCUSSION/CONCLUSIONS:Neighborhood deprivation and disorder may increase middle to older adults' risks of dementia. The disorder may adversely affect cognitive health through increasing loneliness. Our results suggest a clear need for dementia prevention targeting upstream neighborhood contexts, including the improvement of neighborhood conditions to foster social integration among residents.

PURPOSE OF REVIEW/OBJECTIVE:We evaluate evidence-based treatments for posttraumatic headache (PTH), a secondary headache disorder resulting from traumatic brain injury (TBI), comprising nearly 4% of all symptomatic headache disorders. Utilizing recent publications, we aim to inform clinicians of current treatment methods. RECENT FINDINGS/RESULTS:There is limited research on PTH treatment. A randomized controlled trial (RCT) of metoclopramide with diphenhydramine for acute PTH found that the treatment group (N = 81) experienced more significant pain improvement than placebo by 1.4 points. For persistent PTH, an open-label study of erenumab (N = 89) found that 28% of participants reported ≥ 50% reduction in moderate-to-severe headache days, but an RCT of fremanezumab showed a non-significant reduction in moderate-to-severe headache days. A randomized crossover study of 40 patients with persistent PTH found that onabotulinum toxin-A decreased cumulative number of headaches/week by 43.3% in the treatment group and increased by 35.1% among placebos. In a study of military veterans with severe posttraumatic stress disorder and persistent/delayed onset PTH (N = 193), patients who received Cognitive Behavioral Therapy reported significant improvements in headache-related disability compared to usual care (aggregate mean HIT-6, -3.4). A transcranial magnetic stimulation (N = 24) study found that 58% of participants with mild TBI-related headache experienced a 50% reduction in headache frequency. New studies indicate promise in improving clinically important outcomes of PTH. However, more research is necessary to determine the optimal treatment and whether combining pharmacologic and nonpharmacologic treatment versus a single modality is more effective.

Exposure to repetitive head impacts (RHIs) in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE) which currently can be diagnosed only at postmortem. American football players are at higher risk of developing CTE given their exposure to RHIs. One promising approach for diagnosing CTE in vivo is to explore known neuropathological abnormalities at postmortem in living individuals using structural magnetic resonance imaging (MRI). MRI brain morphometry was evaluated in 170 male former American football players ages 45-74 years (n = 114 professional; n = 56 college) and 54 same-age unexposed asymptomatic male controls (n = 58 age range 45-74). Cortical thickness and volume of regions of interest were selected based on established CTE pathology findings and were assessed using FreeSurfer. Group differences and interactions with age and exposure factors were evaluated using a generalized least squares model. A separate logistic regression and independent multinomial model were performed to predict each Traumatic Encephalopathy Syndrome (TES) diagnosis core clinical features and provisional level of certainty for CTE pathology using brain regions of interest. Former college and professional American football players (combined) showed significant cortical thickness and/or volume reductions compared to unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula temporal pole and superior frontal gyrus. Post-hoc analyses identified group-level differences between former professional players and unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula and superior frontal gyrus. Former college players showed significant volume reductions in the hippocampus amygdala and superior frontal gyrus compared to the unexposed asymptomatic controls. We did not observe age-by-group interactions for brain morphometric measures. Interactions between morphometry and exposure measures were limited to a single significant positive association between the age of first exposure to organized tackle football and right insular volume. We found no significant relationship between brain morphometric measures and the TES diagnosis core clinical features and provisional level of certainty for CTE pathology outcomes. These findings suggest that MRI morphometrics detects abnormalities in individuals with a history of RHI exposure that resemble the anatomic distribution of pathological findings from postmortem CTE studies. The lack of findings associating MRI measures with exposure metrics (except for one significant relationship) or TES diagnosis and core clinical features suggests that brain morphometry must be complemented by other types of measures to characterize individuals with RHIs.

Despite well-studied associations of state firearm laws with lower state- and county-level firearm homicide, there is a shortage of studies investigating differences in the effects of distinct state firearm law categories on various cities within the same state using identical methods. We examined associations of 5 categories of state firearm laws-pertaining to buyers, dealers, domestic violence, gun type/trafficking, and possession-with city-level firearm homicide, and then tested differential associations by city characteristics. City-level panel data on firearm homicide cases of 78 major cities from 2010 to 2020 was assessed from the Centers for Disease Control and Prevention's National Vital Statistics System. We modeled log-transformed firearm homicide rates as a function of firearm law scores, city, state, and year fixed effects, along with time-varying city-level confounders. We considered effect measure modification by poverty, unemployment, vacant housing, and income inequality. A one z-score increase in state gun type/trafficking, possession, and dealer law scores was associated with 25% (95% confidence interval [CI]:-0.37,-0.1), 19% (95% CI:-0.29,-0.07), and 17% (95% CI:-0.28, -0.4) lower firearm homicide rates, respectively. Protective associations were less pronounced in cities with high unemployment and high housing vacancy, but more pronounced in cities with high income inequality. In large US cities, state-level gun type/trafficking, possession, and dealer laws were associated with lower firearm homicide rates, but buyers and domestic violence laws were not. State firearm laws may have differential effects on firearm homicides based on city characteristics, and city-wide policies to enhance socioeconomic drivers may add benefits of firearm laws.

BACKGROUND:Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a demyelinating disorder that most commonly presents with optic neuritis (ON) and affects children more often than adults. We report 8 pediatric patients with MOG-associated ON and characterize focal optical coherence tomography (OCT) abnormalities over time that help distinguish this condition from the trajectories of other demyelinating disorders. These OCT findings are examined in the context of longitudinal visual function testing. METHODS:This is a retrospective case series of 8 pediatric patients with MOG-associated ON who were referred for neuro-ophthalmic evaluation. Longitudinal data for demographics, clinical history, physical examination, and OCT obtained in the course of clinical evaluations were collected through retrospective medical record review. RESULTS:Patients demonstrated acute peripapillary retinal nerve fiber layer (RNFL) thickening in one or both eyes, consistent with optic disc swelling. This was followed by steady patterns of average RNFL thinning, with 9 of 16 eyes reaching significantly low RNFL thickness using OCT platform reference databases (P < 0.01), accompanied by paradoxical recovery of high-contrast visual acuity (HCVA) in every patient. There was no correlation between HCVA and any OCT measures, although contrast sensitivity (CS) was associated with global thickness, PMB thickness, and nasal/temporal (N/T) ratio, and color vision was associated with PMB thickness. There was a lower global and papillomacular bundle (PMB) thickness (P < 0.01) in clinically affected eyes compared with unaffected eyes. There was also a significantly higher N:T ratio in clinically affected eyes compared with unaffected eyes in the acute MOG-ON setting (P = 0.03), but not in the long-term setting. CONCLUSIONS:MOG shows a pattern of prominent retinal atrophy, as demonstrated by global RNFL thinning, with remarkable preservation of HCVA but remaining deficits in CS and color vision. These tests may be better clinical markers of vision changes secondary to MOG-ON. Of the OCT parameters measured, PMB thickness demonstrated the most consistent correlation between structural and functional measures. Thus, it may be a more sensitive marker of clinically significant retinal atrophy in MOG-ON. The N:T ratio in acute clinically affected MOG-ON eyes in our study was higher than the N:T ratio of neuromyelitis optica (NMO)-ON eyes and similar to the N:T ratio in multiple sclerosis (MS)-ON eyes as presented in the prior literature. Therefore, MOG may share a more similar pathophysiology to MS compared with NMO.