Faculty Bibliography

INTRODUCTION/UNASSIGNED:Alzheimer's Disease (AD) typically starts in the medial temporal lobe, then develops into a neurodegenerative cascade which spreads to other brain regions. People with subjective cognitive decline (SCD) are more likely to develop dementia, especially in the presence of amyloid pathology. Thus, we were interested in the white matter microstructure of the medial temporal lobe in SCD, specifically the lower cingulum bundle that leads into the hippocampus. Diffusion tensor imaging (DTI) has been shown to differentiate SCD participants who will progress to mild cognitive impairment from those who will not. However, the biology underlying these DTI metrics is unclear, and results in the medial temporal lobe have been inconsistent. METHODS/UNASSIGNED: = 325, 127 SCD). Diffusion MRI was processed to generate regional and voxel-wise diffusion tensor values in bilateral lower cingulum white matter, while T1-weighted MRI was processed to generate regional volume and cortical thickness in the medial temporal lobe white matter, entorhinal cortex, temporal pole, and hippocampus. RESULTS/UNASSIGNED:SCD participants had thinner cortex in bilateral entorhinal cortex and right temporal pole. No between-group differences were noted for any of the microstructural metrics of the lower cingulum. However, correlations with delayed story recall were significant for all diffusion microstructure metrics in the right lower cingulum in SCD, but not in controls, with a significant interaction effect. Additionally, the SCD group showed an accelerated aging effect in bilateral lower cingulum with MD, AxD, and RD. DISCUSSION/UNASSIGNED:The diffusion profiles observed in both interaction effects are suggestive of a mixed neuroinflammatory and neurodegenerative pathology. Left entorhinal cortical thinning correlated with decreased FA and increased RD, suggestive of demyelination. However, right entorhinal cortical thinning also correlated with increased AxD, suggestive of a mixed pathology. This may reflect combined pathologies implicated in early AD. DTI was more sensitive than cortical thickness to the associations between SCD, memory, and age. The combined effects of mixed pathology may increase the sensitivity of DTI metrics to variations with age and cognition.

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.

BACKGROUND/UNASSIGNED:Lumbar synovial cysts (LSC), best diagnosed on MR studies, may cause symptoms/signs ranging from unilateral radiculopathy to cauda equina compressive syndromes. Attempts at percutaneous treatment of LSC typically fail. Rather, greater safety/efficacy is associated with direct surgical resection with/without fusion. METHODS/UNASSIGNED:Treatment of LSC with percutaneous techniques, including cyst aspiration/perforation, injection (i.e., with/without steroids, saline/other), dilatation, and/or disruption/bursting, classically fail. This is because LSCs' tough, thickened, and adherent fibrous capsules cause extensive thecal sac/nerve root compression, and contain minimal central "fluid" (i.e., "crank-case" and non-aspirable). Multiple percutaneous attempts at decompression, therefore, typically cause several needle puncture sites risking dural tears (DT)/cerebrospinal fluid (CSF) leaks, direct root injuries, failure to decompress the thecal sac/nerve roots, infections, hematomas, and over the longer-term, adhesive arachnoiditis. RESULTS/UNASSIGNED:Alternatively, many studies document the success of direct or even partial resection of LSC (i.e., partial removal with marked cyst/dural adhesions with shrinking down the remnant of capsular tissue). Surgical decompressions of LSC, ranging from focal laminotomies to laminectomies, may or may not warrant additional fusions. CONCLUSIONS/UNASSIGNED:Symptomatic LSC are best managed with direct or even partial operative resection/decompression with/without fusion. The use of varying percutaneous techniques classically fails, and increases multiple perioperative risks.

BACKGROUND/UNASSIGNED:The literature documents that laminoforaminotomy (CLF), whether performed open, minimally invasively, or microendoscopically, is safer than anterior cervical diskectomy/fusion (ACDF) for lateral cervical disease. METHODS/UNASSIGNED:ACDF for lateral cervical disc disease and/or spondylosis exposes patients to multiple major surgical risk factors not encountered with CLF. These include; carotid artery or jugular vein injuries, esophageal tears, dysphagia, recurrent laryngeal nerve injuries, tracheal injuries, and dysphagia. CLF also exposes patients to lower rates of vertebral artery injury, dural tears (DT)/cerebrospinal fluid fistulas, instability warranting fusion, adjacent segment disease (ASD), plus cord and/or nerve root injuries. RESULTS/UNASSIGNED:Further, CLF vs. ACDF for lateral cervical pathology offer reduced tissue damage, operative time, estimated blood loss (EBL), length of stay (LOS), and cost. CONCLUSION/UNASSIGNED:CLFs', whether performed open, minimally invasively, or microendoscopically, offer greater safety, major pros with few cons, and decreased costs vs. ACDF for lateral cervical disease.

ALS shows complex genetic inheritance patterns. In about 5% to 10% of cases, there is a family history of ALS or a related condition such as frontotemporal dementia in a first or second degree relative, and for about 80% of such people a pathogenic gene variant can be identified. Such variants are also seen in people with no family history because of factor influencing the expression of genes, such as age. Genetic susceptibility factors also contribute to risk, and the heritability of ALS is between 40% and 60%. The genetic variants influencing ALS risk include single base changes, repeat expansions, copy number variants, and others. Here we review what is known of the genetic landscape and architecture of ALS.

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.

BACKGROUND/UNASSIGNED:Direct-to-participant online reporting facilitates the conduct of clinical research by increasing access and clinically meaningful patient engagement. OBJECTIVE/UNASSIGNED:We assessed feasibility of online data collection from adults with diagnosed Huntington's disease (HD) who directly reported their problems and impact in their own words. METHODS/UNASSIGNED:Data were collected online from consenting United States residents who self-identified as 1) having been diagnosed with Huntington's disease, 2) able to ambulate independently, and 3) self-sufficient for most daily needs. Data for this pilot study were collected using the Huntington Study Group myHDstory online research platform. The Huntington Disease Patient Report of Problems (HD-PROP), an open-ended questionnaire, was used to capture verbatim bothersome problems and functional impact. Natural language processing, human-in-the-loop curation of verbatim reports involving clinical and experience experts, and machine learning classified verbatim-reports into clinically meaningful symptoms. RESULTS/UNASSIGNED:All 8 questionnaires in the online pilot study were completed by 345 participants who were 60.9% men, 34.5±9.9 (mean±SD) years old, and 9.5±8.4 years since HD diagnosis. Racial self-identification was 46.4% Caucasian, 28.7% African American, 15.4% American Indian/Alaska Native, and 9.5% other. Accuracy of verbatim classification was 99%. Non-motor problems were the most frequently reported symptoms; depression and cognitive impairment were the most common. CONCLUSIONS/UNASSIGNED:Online research participation was feasible for a diverse cohort of adults who self-reported an HD diagnosis and predominantly non-motor symptoms related to mood and cognition. Online research tools can help inform what bothers HD patients, identify clinically meaningful outcomes, and facilitate participation by diverse and under-represented populations.

OBJECTIVES/OBJECTIVE:The primary objective of this proposed guideline is to update the prior 2016 guideline on parenteral pharmacotherapies for the management of adults with a migraine attack in the emergency department (ED). METHODS:We will conduct an updated systematic review and meta-analysis using the 2016 guideline methodology to provide clinical recommendations. The same search strategy will be used for studies up to 2023, with a new search strategy added to capture studies of nerve blocks and sphenopalatine blocks. Medline, Embase, Cochrane, clinicaltrials.gov, and the World Health Organization International Clinical Trial Registry Platform will be searched. Our inclusion criteria consist of studies involving adults with a diagnosis of migraine, utilizing medications administered intravenously, intramuscularly, or subcutaneously in a randomized controlled trial design. Two authors will perform the selection of studies based on title and abstract, followed by a full-text review. A third author will intervene in cases of disagreements. Data will be recorded in a standardized worksheet and subjected to verification. The risk of bias will be assessed using the American Academy of Neurology tool. When applicable, a meta-analysis will be conducted. The efficacy of medications will be evaluated, categorizing them as "highly likely," "likely", or "possibly effective" or "ineffective." Subsequently, clinical recommendations will be developed, considering the risk associated with the medications, following the American Academy of Neurology recommendation development process. RESULTS:The goal of this updated guideline will be to provide guidance on which injectable medications, including interventional approaches (i.e., nerve blocks, sphenopalatine ganglion), should be considered effective acute treatment for adults with migraine who present to an ED. CONCLUSIONS:The methods outlined in this protocol will be used in the design of a future systematic review and meta-analysis-informed guideline, which will then be assessed by and submitted for endorsement by the American Headache Society.