Faculty Bibliography

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.

The emergence of liquid biopsy technologies holds great promise in the cancer setting, including in pediatric central nervous system (CNS) tumors. In contrast to broad lower-depth sequencing, commonly referred to as low pass whole genome sequencing (WGS), targeted platforms with a higher depth of coverage have also been established. Here, we review targeted liquid biopsy techniques with applicability to pediatric CNS tumors. These include polymerase chain reaction (PCR), both droplet digital PCR and reverse transcription-based PCR, Sanger sequencing, and next-generation sequencing approaches that incorporate amplicon- and hybrid capture-based methods. The goal of this paper is to facilitate an understanding of these targeted techniques and provide a context for clinical relevance within disease categories, as well as a discussion on optimizing real-world implementation for pediatric CNS tumors.

INTRODUCTION/BACKGROUND:The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. METHODS:The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. RESULTS:126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. DISCUSSION/CONCLUSIONS:Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

BACKGROUND/UNASSIGNED:Our review of 12 articles for this perspective showed the frequency of intraoperative thoracic and/or lumbar CSF fistulas/dural tears (DT) ranged from 2.6% - 8% for primary surgical procedures. Delayed postoperative CSF leak/DT were also diagnosed in 0.83% (17/2052 patients) to 14.3% (2/14 patients) of patients undergoing thoracic and/or lumbar procedures. Further, the rate of recurrent postoperative CSF leaks/DT varied from 13.3% (2/15 patients) to 33.3% (4/12 patients). METHODS/UNASSIGNED:Intraoperative, postoperative delayed, and recurrent postoperative traumatic postsurgical thorac CSF leaks/DT can be limited by performing initially sufficient operative decompressions and/or decompressions/fusions (i.e., utilizing adequate open exposures vs. inadequate minimally invasive (MI) approaches). The incidence of CSF leaks/DT can be further reduced by spine surgeons' utilization of operating microscopes, and their avoiding routine attempts at total synovial cyst excision and/or complete resection of hypertrophied/ossified yellow ligament in the presence of significant dural adhesions. RESULTS/UNASSIGNED:Multiple CSF leak/CT repair techniques included; using interrupted, non-resorbable sutures for direct dural repairs (i.e. 7-0 Gore-Tex sutures where the suture is larger than the needle thus plugging needle holes), and adding where needed muscle patch grafts, microfibrillar collagen, the rotation of Multifidus muscle pedicle flaps, fibrin sealants (FS)/fibrin glues (FG), lumbar drains (LD), and/or lumbo-peritoneal (LP) shunts. CONCLUSION/UNASSIGNED:Intraoperative, postopertive delayed, and/or recurrent postoperative thorac and/or lumbar traumatic surgical CSF leaks can be reduced by choosing to initially perform the appropriately extensive open operative decompressions and/or decompresssions/fusions. It is critical to use an operating microscope, non-resorbable interrupted sutures, and where necessary, muscle patch grafts, microfibrillar collagen, the rotation of Multifidus Muscle Pedicle Flaps, FS/FG, LD, and/or LP shunts.

INTRODUCTION/UNASSIGNED:Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique with simultaneous (during stimulation) and cumulative effects (after repeated sessions) on blood flow and neuronal metabolism. These effects remain mostly unclear especially in multiple sclerosis (MS). This work aims to elucidate brain metabolic and hemodynamic underpinnings of tDCS and its potential therapeutic impact in MS patients using quantitative tDCS-MRI. METHODS/UNASSIGNED:) were obtained at pre-tDCS, during-tDCS and post-tDCS. RESULTS/UNASSIGNED:and CBF in pre-tDCS follow up, reaching the magnitudes measured at baseline during-tDCS. DISCUSSION/UNASSIGNED:TDCS induces an acute surge in metabolic activity persisting immediately after the stimulation is removed. Moreover, treatment composed of repeated tDCS-aCT paired sessions contributes to establishing long-lasting increases in neuronal activity.

INTRODUCTION/UNASSIGNED:The pathophysiology of idiopathic intracranial hypertension (IIH) is not fully characterized, and less is known about its development in transgender patients. Several cases of IIH in transgender patients have been reported, but fewer cases have been published that identify a cerebrospinal fluid (CSF) leak as a complication of IIH in this population. These patients can serve as an important study population, as an association between exogenous testosterone use in karyotypical females and development of IIH may support a hormonally mediated mechanism of development of this disease. CASE PRESENTATION/UNASSIGNED:) female-to-male transgender patient on exogenous testosterone for 15 years who presented with 1 month of acute or chronic headache with profuse rhinorrhea. Fundoscopic exam revealed disk pallor and edema consistent with a Frisen grade 3 papilledema. Nasal secretion was positive for beta-2 transferrin, consistent with CSF. Computed tomography head demonstrated a 5-mm defect in the medial left middle cranial fossa, bilateral optic nerve prominence and tortuosity, and abnormal arachnoid granulations concerning for IIH. After a successful endoscopic endonasal repair of the left lateral sphenoid recess leak, our patient continued to report headaches, was started on acetazolamide, and noted improvement in symptoms. CONCLUSION/UNASSIGNED:The case described herein further supports the growing body of evidence that implicates a hormonal mechanism of action in the development of IIH. Importantly, it also addresses the need for increased study and conversation about rare neurologic diseases in transgender patients.

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.

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.

BACKGROUND AND PURPOSE/OBJECTIVE:The purpose of this study is to evaluate the feasibility of using 3-dimensional (3D) ultra-short echo time (UTE) radial imaging method for measurement of the permeability of the blood-brain barrier (BBB) to gadolinium-based contrast agent. In this study, we propose to use the golden-angle radial sparse parallel (GRASP) method with 3D center-out trajectories for UTE, hence named as 3D UTE-GRASP. We first examined the feasibility of using 3D UTE-GRASP dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) for differentiating subtle BBB disruptions induced by focused ultrasound (FUS). Then, we examined the BBB permeability changes in Alzheimer's disease (AD) pathology using Alzheimer's disease transgenic mice (5xFAD) at different ages. METHODS:For FUS experiments, we used four Sprague Dawley rats at similar ages where we compared BBB permeability of each rat receiving the FUS sonication with different acoustic power (0.4-1.0 MPa). For AD transgenic mice experiments, we included three 5xFAD mice (6, 12, and 16 months old) and three wild-type mice (4, 8, and 12 months old). RESULTS:The result from FUS experiments showed a progressive increase in BBB permeability with increase of acoustic power (p < .05), demonstrating the sensitivity of DCE-MRI method for detecting subtle changes in BBB disruption. Our AD transgenic mice experiments suggest an early BBB disruption in 5xFAD mice, which is further impaired with aging. CONCLUSION/CONCLUSIONS:The results in this study substantiate the feasibility of using the proposed 3D UTE-GRASP method for detecting subtle BBB permeability changes expected in neurodegenerative diseases, such as AD.