Faculty Bibliography

PURPOSE/OBJECTIVE:We describe a case of bilateral, multiple, branch retinal artery occlusions (BRAO) associated with carotid webs. METHODS:A thorough chart review was conducted for the patient. Relevant literature was systematically reviewed. RESULTS:Eight cases of fibromuscular dysplasia (FMD) associated with retinal artery occlusions have been reported. Two additional cases of FMD with other ocular involvement have been described. No cases of carotid webs associated with retinal artery occlusions were found. CONCLUSION/CONCLUSIONS:Carotid webs, an uncommon variant of FMD, are a recognized causative etiology of arterial, ischemic stroke. The case described here of bilateral, multifocal BRAOs represents a unique manifestation of this variant of FMD. This diagnosis should be considered in the setting of an otherwise unrevealing BRAO workup, as recognition of this association may be sight and life-saving.

BACKGROUND:Visual symptoms are common after concussion. Rapid automatized naming (RAN) tasks are simple performance measures that demonstrate worse time scores in the setting of acute or more remote injury. METHODS:We evaluated the capacity for the Mobile Universal Lexicon Evaluation System (MULES) and Staggered Uneven Number (SUN) testing to be feasibly administered during preseason testing in a cohort of youth ice hockey athletes using a novel computerized app, the Mobile Integrated Cognitive Kit (MICK). Participants from a youth hockey league underwent preseason testing. RESULTS:Among 60 participants, the median age was 13 years (range 6-17). The median best time for the MULES was 49.8 seconds (range = 34.2-141.0) and the median best time for the SUN was 70.1 (range = 36.6-200.0). As is characteristic of timed performance measures, there were learning effects between the first and second trials for both the MULES (median improvement = 10.6 seconds, range = -32.3 to 92.0, P < 0.001, Wilcoxon signed-rank test) and SUN (median improvement = 2.4 seconds, range= -8.0 to 15.1, P = 0.001, Wilcoxon signed-rank test). Age was a predictor of best baseline times, with longer (worse) times for younger participants for MULES (P < 0.001, rs = -0.67) and SUN (P < 0.001, rs = -0.54 Spearman rank correlation). Degrees of learning effect did not vary with age (P > 0.05, rs = -0.2). CONCLUSIONS:Vision-based RAN tasks, such as the MULES and SUN, can be feasibly administered using the MICK app during preseason baseline testing in youth sports teams. The results suggest that more frequent baseline tests are necessary for preadolescent athletes because of the relation of RAN task performance to age.

OBJECTIVE:The ongoing war in Ukraine has introduced many challenges to an already overburdened and resource-limited medical system. Longitudinal collaborations, material support, educational outreach, and surgical mentorship are essential for improving outcomes and standards of neurosurgical care in extreme settings such as in times of war. METHODS:Operating in Ukraine since 2016 through the coordination of Razom, the Co-Pilot Project has organized multiple United States-based mission trips to Ukraine to support local physicians during wartime, including a trip between April and May of 2023. RESULTS:A team of two anesthesiologists, two neurosurgeons, a neurointerventional radiologist, and an industry representative providing technical expertise aided in the instruction and performance of complex neurosurgical and neurovascular procedures by Ukrainian physicians at St. Panteleimon Hospital and St. Nicholas Children's Hospital in Lviv. Such efforts are crucial for helping to address the sharp rise in elective neurosurgical volume caused by the increase in internally displaced persons in Western Ukraine since February 2022. In an illustrative case, the authors provide an in-depth description of a foramen magnum meningioma resection via a far lateral craniotomy in a 48-year-old female. CONCLUSIONS:Despite the supply shortages and logistical challenges brought on by war, the Co-Pilot Project continues to utilize a long-term approach to continually improve the operative capabilities of Ukrainian neurosurgeons through both in-person and virtual collaborations. It is hoped that the lessons learned from a recent trip to Ukraine will help to inform and inspire other global neurosurgery initiatives in the future.

INTRODUCTION/BACKGROUND:Disturbances in microvascular flow dynamics are hypothesized to precede the symptomatic phase of Alzheimer's disease (AD). However, evidence in presymptomatic AD remains elusive, underscoring the need for therapies targeting these early vascular changes. METHODS:We employed a multimodal approach, combining in vivo optical imaging, molecular techniques, and ex vivo magnetic resonance imaging, to investigate early capillary dysfunction in C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax (Tg-SwDI) mice without memory impairment. We also assessed the efficacy of carbonic anhydrase inhibitors (CAIs) in preventing capillary flow disturbances. RESULTS:Our study revealed capillary flow disturbances associated with alterations in capillary morphology, adhesion molecule expression, and amyloid beta (Aβ) load in 9- to 10-month-old Tg-SwDI mice without memory impairment. CAI treatment ameliorated these capillary flow disturbances, enhanced oxygen availability, and reduced Aβ load. DISCUSSION/CONCLUSIONS:These findings underscore the importance of capillary flow disturbances as early biomarkers in presymptomatic AD and highlight the potential of CAIs for preserving vascular integrity in the early stages of AD. HIGHLIGHTS/CONCLUSIONS:Uncovered early capillary dysfunction in a presymptomatic Alzheimer's disease (AD) mouse model. Evidence linking capillary stalls and capillary dysfunction with oxygen delivery issues in AD. Novel use of carbonic anhydrase inhibitors to prevent early capillary flow disturbances in AD.

The objective of this study was to evaluate the effect of seletracetam (SEL), a potent modulator of synaptic vesicle glycoprotein 2A (SV2A), in patients with photoparoxysmal EEG response (PPR) to intermittent photic stimulation (IPS) as proof-of-principle of efficacy in patients with epilepsy. In this multicenter, single-blind Phase II study, adults with photosensitive epilepsy, with/without concomitant antiseizure medication therapy, underwent IPS under 3 eye conditions (at eye closure, eyes closed and eyes open) after a single oral dose of placebo (day - 1) or SEL (day 1; 0.5, 1, 2, 4, 10, or 20 mg). Complete suppression was a standardized photosensitivity range reduction to 0 over ≥ 1 time points for all eye conditions. Partial suppression was a ≥ 3-point reduction over ≥ 3 testing times vs the same time points on day - 1 in ≥ 1 eye condition. In addition, pharmacokinetics and safety were assessed. Of 27 evaluable patients, 9 reentered to receive a 2nd dosing 1-6 months later, providing a total of 36 individual exposures. At all doses administered - even the lowest -, several subjects reached a complete abolishment of PPR, with a rapid onset of effect. Overall, complete abolishment of PPR was obtained in 40-71 % of the patients; the effect increasing with the dose. In terms of effective doses to suppress PPR, SEL was at least 1,500 times more potent than levetiracetam and 10-20 times more potent than brivaracetam. Adverse events of SEL, including dizziness and somnolence, were mild to moderate. Pharmacokinetics of SEL demonstrated rapid absorption and a linear dose:plasma level relationship. This proof-of-principle study demonstrates that - based on our own experience - SEL is the most potent compound ever tested in the photosensitivity model.

BACKGROUND/UNASSIGNED:This systematic review analyzes the impact of COVID-19 on dementia patients' functional, cognitive, neuropsychiatric, and health related outcomes. It hypothesizes that dementia patients infected with SARS-CoV-2experience more pronounced deterioration compared to those who are uninfected. METHODS/UNASSIGNED:Research from 01/03/2020 to 07/10/2023 was conducted using Medline, Web of Science, and Embase databases, and adhering to PRISMA guidelines and the PICO framework. The study aimed to determine if SARS-CoV-2 infection is associated with worse outcomes in dementia patients. The protocol is registered in PROSPERO (CRD42022352481), and bias was evaluated using the Newcastle-Ottawa Scale. RESULTS/UNASSIGNED:Among 198 studies reviewed, only three met the criteria. Chen et al. (2023) identified higher mortality in SARS-CoV-2-infected dementia patients, while Merla et al. (2023) observed faster cognitive decline in infected individuals with increased hospital admissions. Additionally, Cascini et al. (2022) reported an increased risk of infection and significantly elevated mortality in dementia patients, highlighting comorbidities and antipsychotic medication use as key risk factors. CONCLUSION/UNASSIGNED:These limited data suggest higher mortality and cognitive decline in dementia patients following COVID-19, underscoring the need for extensive research in this area.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Low sun and ultraviolet radiation (UVR) exposures have been associated with increased risk of developing pediatric-onset multiple sclerosis (MS); however, their effect on disease course has not been well characterized. We primarily investigated whether there was an association between time spent in the sun in early childhood and risk of relapse in pediatric MS. We secondarily investigated the effect of sun exposure during more recent periods on risk of relapse. METHODS:We conducted a multicenter cohort study of participants with pediatric-onset MS recruited from 18 pediatric MS clinics across the United States between November 1, 2011, and July 1, 2017. Relapses were identified prospectively after study enrollment; relapses preceding study enrollment were entered retrospectively. Time spent in the sun at various periods of life was measured using a detailed environmental questionnaire, and ambient UVR exposure was determined using zip codes. Multivariable Cox regression models were used to assess the association between time spent in the sun and UVR dose at specific periods of life and the risk of relapse. Models were adjusted for demographic, clinical, and sun exposure-related characteristics. RESULTS:= 0.04). UVR dose and time spent in the sun later in life were not significantly associated with relapse risk. DISCUSSION/CONCLUSIONS:In this large cohort study of children with MS, greater early childhood and prenatal sun exposure time was associated with lower risk of relapse. Further investigation of sun exposure at other periods is needed to better characterize its impact on disease course and guide potential future interventions.

Resective surgery for drug-resistant temporal lobe epilepsy remains underutilized in the United States. While anteromesial temporal lobectomy consistently achieves the highest rates of long-term seizure freedom, it comes with greater risks for memory and language decline. Magnetic resonance imaging-guided laser interstitial thermal therapy and neuromodulation have gained popularity due to perceived lower surgical risk and faster recovery, although they yield lower rates of sustained seizure freedom. Neuromodulation with vagus nerve, deep brain, or responsive neurostimulation provides an option for patients ineligible for resection or ablation, but overall seizure outcomes remain modest. Balancing improved seizure control with open resection against the potential cognitive advantages of less invasive treatments is complex, requiring careful patient selection. Future research must refine these approaches to optimize results. Thoughtful, individualized decision-making, guided by each patient's clinical scenario and goals, is paramount for achieving the best balance between seizure freedom, cognitive preservation, and overall patient outcome.