Faculty Bibliography

Optic neuritis has long been considered a characteristic finding of multiple sclerosis and the initial manifestation of the disorder in about 25% of patients. Approximately 70% of patients will experience optic nerve dysfunction during their disease course.¹.

UNLABELLED:DNA methylation is an essential molecular assay for central nervous system (CNS) tumor diagnostics. While some fusions define specific brain tumors, others occur across many different diagnoses. We performed a retrospective analysis of 219 primary CNS tumors with whole genome DNA methylation and RNA next-generation sequencing. DNA methylation profiling results were compared with RNAseq detected gene fusions. We detected 105 rare fusions involving 31 driver genes, including 23 fusions previously not implicated in brain tumors. In addition, we identified 6 multi-fusion tumors. Rare fusions and multi-fusion events can impact the diagnostic accuracy of DNA methylation by decreasing confidence in the result, such as BRAF, RAF, or FGFR1 fusions, or result in a complete mismatch, such as NTRK, EWSR1, FGFR, and ALK fusions. IMPLICATIONS/UNASSIGNED:DNA methylation signatures need to be interpreted in the context of pathology and discordant results warrant testing for novel and rare gene fusions.

Background: Past research suggests that subjective cognitive decline serves as an early and potentially important indicator that individuals may be at risk for future cognitive decline or neurodegenerative conditions. However, there is a dearth of studies on factors influencing the experience of subjective cognitive decline in Black Americans, especially in Black American men. Objective: The current study explored correlates of subjective cognitive decline in Black American men. Participants: A total of 117 Black American men, with a mean age of 38.5 (SD = 7.14) years, participated in the study. Measurement: Participants completed a survey that assessed their demographic characteristics, self-rated health, neighborhood problems, length of residency in neighborhood, bodily symptoms, sleep comorbidities, sleep difficulties, and subjective cognitive decline. Linear regression analyses was performed and standardized beta coefficients were reported to describe the estimated independent effect of the predictor variables. Results: We found that socioecomic status (β = −.222, p=.003), bodily symptoms (β =.246, p=.005), length of residency in neighborhood (β =.157, p=.029), and sleep difficulties (β =.305, p<.001) were significant correlates of subjective cognitive decline among Black American men. Conclusion: These findings underscore the intricate roles of socioeconomic status, bodily symptoms, neighborhood factors, and sleep health in shaping subjective cognitive experiences in this population. Research on subjective cognitive decline can contribute to the early identification of individuals at risk for cognitive decline, allowing for timely interventions, lifestyle modifications, and potential preventive measures.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Instrumented spinal fusion constructs sometimes fail because of fatigue loading, frequently necessitating open revision surgery. Favorable outcomes after percutaneous juxtapedicular cement salvage (perc-cement salvage) of failing instrumentation have been described; however, this approach is not widely known among spine surgeons , and its biomechanical properties have not been evaluated. We report our institutional experience with perc-cement salvage and investigate the relative biomechanical strength of this technique as compared with 3 other common open revision techniques. METHODS:A retrospective chart review of patients who underwent perc-cement salvage was conducted. Biomechanical characterization of revision techniques was performed in a cadaveric model of critical pedicle screw failure. Three revision cohorts involved removal and replacement of hardware: (1) screw upsizing, (2) vertebroplasty, and (3) fenestrated screw with cement augmentation. These were compared with a cohort with perc-cement salvage performed using a juxtapedicular trajectory with the failed primary screw remaining engaged in the vertebral body. RESULTS:Ten patients underwent perc-cement salvage from 2018 to 2022 to address screw haloing and/or endplate fracture threatening construct integrity. Pain palliation was reported by 8/10 patients. Open revision surgery was required in 4/10 patients, an average of 8.9 months after the salvage procedure (range 6.2-14.7 months). Only one revision was due to progressive hardware dislodgement. The remainder avoided open revision surgery through an average of 1.9 years of follow-up. In the cadaveric study, there were no significant differences in pedicle screw pullout strength among any of the revision cohorts. CONCLUSION/CONCLUSIONS:Perc-cement salvage of failing instrumentation is reasonably efficacious. The technique is biomechanically noninferior to other revision strategies that require open surgery for removal and replacement of hardware. Open revision surgery may be avoided by perc-cement salvage in select cases.

Former American football players are at risk for developing traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). The objective of this study was to determine whether hyposmia is present in traumatic encephalopathy syndrome. The study included 119 former professional American football players, 60 former college football players, and 58 same age asymptomatic unexposed men from the DIAGNOSE CTE Research Project. All subjects included in the analysis had completed the Brief Smell Identification Test (B-SIT). Traumatic encephalopathy syndrome and the level of CTE certainty were diagnosed using the 2021 NINDS consensus diagnostic criteria. TES is categorized antemortem by provisional levels of increasing CTE certainty: Suggestive, Possible, and Probable. Former players who had traumatic encephalopathy syndrome and Probable CTE had lower B-SIT scores than those with TES and Suggestive CTE. Hyposmia was more likely in the former players with TES who were either CTE Possible or Probable than in those who did not have TES or had TES but were less likely to have CTE, CTE Suggestive. There was no difference in B-SIT scores between all former players versus unexposed men nor overall between the football players with and without TES. We conclude that lower B-SIT scores may be a clinical biomarker for underlying CTE in former American football players.

Background: The Visual Symptoms and Signs Screen (V-SASS) is a tool to identify vision deficits and facilitate referrals to vision specialists. The study objectives were to determine feasibility and clinician perspectives of the V-SASS. Methods: Prospective, multisite study with 141 new-onset stroke participants. After V-SASS administration, feasibility and predictive success were assessed. Results: The V-SASS identified vision symptoms and signs with high feasibility (>75%). Of those who screened positive, 93.1% had deficits in visual function or functional vision. Conclusions: The V-SASS was found to be feasible in multiple settings and accurately identify vision deficits and appropriately trigger vision referrals.

IMPORTANCE/UNASSIGNED:The association of fetal exposure to antiseizure medications (ASMs) with outcomes in childhood are not well delineated. OBJECTIVE/UNASSIGNED:To examine the association of fetal ASM exposure with subsequent adaptive, behavioral or emotional, and neurodevelopmental disorder outcomes at 2, 3, and 4.5 years of age. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational cohort study conducted at 20 epilepsy centers in the US. A total of 456 pregnant women with epilepsy or without epilepsy were enrolled from December 19, 2012, to January 13, 2016. Children of enrolled women were followed up with formal assessments at 2, 3, 4.5, and 6 years of age. Statistical analysis took place from August 2022 to May 2023. EXPOSURES/UNASSIGNED:Exposures included mother's epilepsy status as well as mother's ASM blood concentration in the third trimester (for children of women with epilepsy). Women with epilepsy were enrolled regardless of ASM regimen. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was the Adaptive Behavior Assessment System, Third Edition (ABAS-3) General Adaptive Composite (GAC) score among children at 4.5 years of age. Children of women with epilepsy and children of women without epilepsy were compared, and the associations of ASM exposures with outcomes among exposed children were assessed. Secondary outcomes involved similar analyses of other related measures. RESULTS/UNASSIGNED:Primary analysis included 302 children of women with epilepsy (143 boys [47.4%]) and 84 children of women without epilepsy (45 boys [53.6%]). Overall adaptive functioning (ABAS-3 GAC score at 4.5 years) did not significantly differ between children of women with epilepsy and children of women without epilepsy (parameter estimate [PE], 0.4 [95% CI, -2.5 to 3.4]; P = .77). However, in adjusted analyses, a significant decrease in functioning was seen with increasing third-trimester maximum ASM blood concentrations (PE, -7.8 [95% CI, -12.6 to -3.1]; P = .001). This decrease in functioning was evident for levetiracetam (PE, -18.9 [95% CI, -26.8 to -10.9]; P < .001) and lamotrigine (PE, -12.0 [95% CI, -23.7 to -0.3]; P = .04), the ASMs with sample sizes large enough for analysis. Results were similar with third-trimester maximum daily dose. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This study suggests that adaptive functioning of children of women with epilepsy taking commonly used ASMs did not significantly differ from that of children of women without epilepsy, but there was an exposure-dependent association of ASMs with functioning. Thus, psychiatric or psychological screening and referral of women with epilepsy and their offspring are recommended when appropriate. Additional research is needed to confirm these findings.