Faculty Bibliography

OBJECTIVE/UNASSIGNED:To delineate the trend of use of botulinum toxin, including onabotulinum toxinA (OTA), in active military personnel and veterans with the diagnoses of migraine and post-traumatic headache (PTH) and describe the efficacy of botulinum toxin administration. BACKGROUND/UNASSIGNED:Service members and veterans represent a unique population in the medical management of headache disorders, particularly migraine. They exhibit higher susceptibility to pain of greater intensity and longer durations, possibly due to their history of exposure to combat, trauma, and the associated psychological stresses. Given the burden and morbid nature of these headache disorders, prophylactic measures to reduce migraine attacks and disability are imperative. Specifically, the use of OTA for migraine prophylaxis has been well validated in chronic migraine. METHODS/UNASSIGNED:The scoping review conformed to guidelines delineated by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The databases Medline, Embase, and Google Scholar were accessed for our literature search, and the time frame of the search was set from database inception to April 1, 2024. RESULTS/UNASSIGNED:A total of 8 articles meeting the inclusion criteria were obtained after screening a total of 43 papers. Studies were primarily conducted in the United States (87.5%), with a single article published on veterans from Taiwan. Study types were mainly retrospective chart reviews with the exception of 2 randomized controlled trials. Chronic migraine was the most common headache diagnosis examined, being assessed in 6 studies, followed by PTH, which was represented in the remaining 2 studies. CONCLUSION/UNASSIGNED:The occupational exposure of service members appears to result in a higher incidence of headache disorders such as chronic migraine and PTH, which are amenable to preventative management such as that with botulinum toxin. Despite its effectiveness, the use of botulinum toxin in treating headaches and craniofacial pain in service members remains under-researched, warranting further exploration in this population, specifically.

INTRODUCTION/UNASSIGNED:Older adults undergoing surgery are at risk of postoperative neurocognitive disorders, prompting the need for preoperative cognitive screening in this population. Traditionally, cognitive screening has been conducted in-person using brief assessment tools such as the Montreal Cognitive Assessment (MoCA) or the Mini-Mental State Examination (MMSE). More comprehensive test batteries, such as the Uniform Data Set (UDS) Neuropsychological Battery, and its remote testing version, the Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 T-cog), have been developed to assess cognitive decline in normal aging and disease conditions, but have not been applied in the perioperative setting. METHODS/UNASSIGNED:We assessed the feasibility of using this remote UDS v3.0 T-cog battery for preoperative cognitive assessment in 81 older adults 65+ scheduled for lower extremity joint replacement surgery. RESULTS/UNASSIGNED:Our results indicate that the UDS v3.0 T-cog achieves 99% completion rates and demonstrates high patient satisfaction. Further, we found 28% of subjects were cognitively impaired in this patient cohort. DISCUSSION/UNASSIGNED:These findings suggest that the UDS v3.0 T-cog is a feasible tool for assessing cognitive function in the older adult perioperative population. To our knowledge, this is the first study to apply this comprehensive remote test battery in the preoperative setting.

Convolutional neural networks (CNN) show great promise for translating decades of research on structural abnormalities in temporal lobe epilepsy into clinical practice. Three-dimensional CNNs typically outperform two-dimensional CNNs in medical imaging. Here we explore for the first time whether a three-dimensional CNN outperforms a two-dimensional CNN for identifying temporal lobe epilepsy-specific features on MRI. Using 1178 T1-weighted images (589 temporal lobe epilepsy, 589 healthy controls) from 12 surgical centres, we trained 3D and 2D CNNs for temporal lobe epilepsy versus healthy control classification, using feature visualization to identify important regions. The 3D CNN was compared to the 2D model and to a randomized model (comparison to chance). Further, we explored the effect of sample size with subsampling, examined model performance based on single-subject clinical characteristics, and tested the impact of image harmonization on model performance. Across 50 datapoints (10 runs with 5-folds each) the 3D CNN median accuracy was 86.4% (35.3% above chance) and the median F1-score was 86.1% (33.3% above chance). The 3D model yielded higher accuracy compared to the 2D model on 84% of datapoints (median 2D accuracy, 83.0%), a significant outperformance for the 3D model (binomial test: P < 0.001). This advantage of the 3D model was only apparent at the highest sample size. Saliency maps exhibited the importance of medial-ventral temporal, cerebellar, and midline subcortical regions across both models for classification. However, the 3D model had higher salience in the most important regions, the ventral-medial temporal and midline subcortical regions. Importantly, the model achieved high accuracy (82% accuracy) even in patients without MRI-identifiable hippocampal sclerosis. Finally, applying ComBat for harmonization did not improve performance. These findings highlight the value of 3D CNNs for identifying subtle structural abnormalities on MRI, especially in patients without clinically identified temporal lobe epilepsy lesions. Our findings also reveal that the advantage of 3D CNNs relies on large sample sizes for model training.

OBJECTIVE/UNASSIGNED:A significant number of patients develop anxiety after stroke. The objective of this study was to identify risk factors for anxiety after hemorrhagic stroke that may facilitate diagnosis and treatment. METHODS/UNASSIGNED:Patients admitted between January 2015 and February 2021 with nontraumatic hemorrhagic stroke (intracerebral [ICH] or subarachnoid [SAH] hemorrhage) were assessed telephonically 3 and 12 months after stroke with the Quality of Life in Neurological Disorders Anxiety Short Form to evaluate the relationships between poststroke anxiety (T score >50) and preclinical social and neuropsychiatric history, systemic and neurological illness severity, and in-hospital complications. RESULTS/UNASSIGNED:Of 71 patients who completed the 3-month assessment, 28 (39%) had anxiety. There was a difference in Glasgow Coma Scale (GCS) scores on admission between patients with anxiety (median=14, interquartile range [IQR]=12-15) and those without anxiety (median=15, IQR=14-15) (p=0.034), and the incidence of anxiety was higher among patients with ICH (50%) than among those with SAH (20%) (p=0.021). Among patients with ICH, anxiety was associated with larger median ICH volume (25 cc [IQR=8-46] versus 8 cc [IQR=3-13], p=0.021) and higher median ICH score (2 [IQR=1-3] versus 1 [IQR=0-1], p=0.037). On multivariable analysis with GCS score, hemorrhage type, and neuropsychiatric history, only hemorrhage type remained significant (odds ratio=3.77, 95% CI=1.19-12.05, p=0.024). Of the 39 patients who completed the 12-month assessment, 12 (31%) had anxiety, and there was a difference in mean National Institutes of Health Stroke Scale scores between patients with (5 [IQR=3-12]) and without (2 [IQR=0-4]) anxiety (p=0.045). There was fair agreement (κ=0.38) between the presence of anxiety at 3 and 12 months. CONCLUSIONS/UNASSIGNED:Hemorrhage characteristics and factors assessed with neurological examination on admission are associated with the development of poststroke anxiety.

BACKGROUND/UNASSIGNED:Loneliness has been declared an "epidemic" associated with negative physical, mental, and cognitive health outcomes such as increased dementia risk. Less is known about the relationship between loneliness and advanced neuroimaging correlates of Alzheimer's disease (AD). OBJECTIVE/UNASSIGNED:To assess whether loneliness was associated with advanced neuroimaging markers of AD using neuroimaging data from Framingham Heart Study (FHS) participants without dementia. METHODS/UNASSIGNED:In this cross-sectional observational analysis, we used functional connectivity MRI (fcMRI), amyloid-β (Aβ) PET, and tau PET imaging data collected between 2016 and 2019 on eligible FHS cohort participants. Loneliness was defined as feeling lonely at least one day in the past week. The primary fcMRI marker was Default Mode Network intra-network connectivity. The primary PET imaging markers were Aβ deposition in precuneal and FLR (frontal, lateral parietal and lateral temporal, retrosplenial) regions, and tau deposition in the amygdala, entorhinal, and rhinal regions. RESULTS/UNASSIGNED:Of 381 participants (mean age 58 [SD 10]) who met inclusion criteria for fcMRI analysis, 5% were classified as lonely (17/381). No association was observed between loneliness status and network changes. Of 424 participants (mean age 58 [SD = 10]) meeting inclusion criteria for PET analyses, 5% (21/424) were lonely; no associations were observed between loneliness and either Aβ or tau deposition in primary regions of interest. CONCLUSIONS/UNASSIGNED:In this cross-sectional study, there were no observable associations between loneliness and select fcMRI, Aβ PET, and tau PET neuroimaging markers of AD risk. These findings merit further investigation in prospective studies of community-based cohorts.

Stem cell therapies are progressively redefining the treatment landscape for a spectrum of neurological and age-related disorders. This review discusses the molecular and functional attributes of stem cells, emphasizing the roles of neural stem cells and mesenchymal stem cells in the context of neurological diseases such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's disease, and Alzheimer's disease. The review also explores the potential of stem cells in addressing the aging process. The paper analyzes stem cells' intrinsic properties of self-renewal, differentiation, and paracrine effects, alongside the importance of laboratory-modified stem cells like induced pluripotent stem cells and transgenic stem cells. Insights into disease-specific stem cell treatments are offered, reviewing both successes and challenges in the field. This includes the translational difficulties from rodent studies to human trials. The review concludes by acknowledging the uncharted territories that warrant further investigation, emphasizing the potential roles of stem cell-derived exosomes and indole-related molecules, and aiming at providing a basic understanding of stem cell therapies.

Primary neuronal cultures are commonly used to study genetic and exogenous factors influencing neuronal development and maturation. During development, neurons undergo robust morphological changes involving expansion of dendritic arbor, formation of dendritic spines, and expression of synaptic proteins. In this chapter, we will cover methodological approaches allowing quantitative assessment of in vitro cultured neurons. Various quantitative characteristics of dendritic arbor can be derived based on immunostaining against anti-microtubule-associated protein 2 followed by dendrite tracing with the SNT plug-in of the FIJI software package. The number and subtypes of dendritic spines can be assessed by double labeling with DiI and Phalloidin iFluor448 followed by laser scanning confocal microscopy analysis. Finally, expression of presynaptic and postsynaptic proteins can be determined by immunohistochemistry and quantification using several available software packages including FIJI and Imaris, which also allows for 3D rendering and statistical displaying of the expression level of synaptic proteins.

Symptoms of autonomic dysfunction are prevalent and can be very debilitating, reducing the quality of life in patients with Parkinson's disease (PD) and other synucleinopathies such as dementia with Lewy bodies and multiple system atrophy. Non-pharmacological therapies are key to effective management and are frequently used alone in patients with mild autonomic symptoms, or in combination with pharmacological therapies in patients with moderate and severe symptoms. This article focuses on non-pharmacological approaches. Our objective was to review the non-drug and non-surgical approaches to treating autonomic symptoms in patients with PD and other synucleinopathies, focusing on cardiovascular, gastrointestinal, and genitourinary autonomic dysfunction. Evidence supporting the effectiveness of non-pharmacological treatment for the management of neurogenic orthostatic hypotension, supine hypertension, constipation, and bladder and sexual dysfunction is available. High-quality prospective trials are scarce, yet some non-pharmacological interventions (e.g., physical counter maneuvers) can be evaluated relatively quickly on an individual basis and often seem effective. The emerging variety of clinical presentations advocates for a stepwise, individualized, and non-pharmacological approach for the management of autonomic symptoms. Often, the first step is to reduce or discontinue drugs that cause or aggravate autonomic symptoms followed by lifestyle measures. While non-pharmacological and non-surgical treatments are available and, in many cases, effective to improve symptoms of autonomic dysfunction in PD and other synucleinopathies, they are often overlooked. Large randomized trials testing and comparing non-pharmacological approaches are warranted.