Faculty Bibliography

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.

Cortical regions supporting speech production are commonly established using neuroimaging techniques in both research and clinical settings. However, for neurosurgical purposes, structural function is routinely mapped peri-operatively using direct electrocortical stimulation. While this method is the gold standard for identification of eloquent cortical regions to preserve in neurosurgical patients, there is lack of specificity of the actual underlying cognitive processes being interrupted. To address this, we propose mapping the temporal dynamics of speech arrest across peri-sylvian cortices by quantifying the latency between stimulation and speech deficits. In doing so, we are able to substantiate hypotheses about distinct region-specific functional roles (e.g. planning versus motor execution). In this retrospective observational study, we analysed 20 patients (12 female; age range 14-43) with refractory epilepsy who underwent continuous extra-operative intracranial EEG monitoring of an automatic speech task during clinical bedside language mapping. Latency to speech arrest was calculated as time from stimulation onset to speech arrest onset, controlling for individual speech rate. Most instances of motor-based arrest (87.5% of 96 instances) were in sensorimotor cortex with mid-range latencies to speech arrest with a distributional peak at 0.47 s. Speech arrest occurred in numerous regions, with relatively short latencies in supramarginal gyrus (0.46 s), superior temporal gyrus (0.51 s) and middle temporal gyrus (0.54 s), followed by relatively long latencies in sensorimotor cortex (0.72 s) and especially long latencies in inferior frontal gyrus (0.95 s). Non-parametric testing for speech arrest revealed that region predicted latency; latencies in supramarginal gyrus and in superior temporal gyrus were shorter than in sensorimotor cortex and in inferior frontal gyrus. Sensorimotor cortex is primarily responsible for motor-based arrest. Latencies to speech arrest in supramarginal gyrus and superior temporal gyrus (and to a lesser extent middle temporal gyrus) align with latencies to motor-based arrest in sensorimotor cortex. This pattern of relatively quick cessation of speech suggests that stimulating these regions interferes with the outgoing motor execution. In contrast, the latencies to speech arrest in inferior frontal gyrus and in ventral regions of sensorimotor cortex were significantly longer than those in temporoparietal regions. Longer latencies in the more frontal areas (including inferior frontal gyrus and ventral areas of precentral gyrus and postcentral gyrus) suggest that stimulating these areas interrupts a higher-level speech production process involved in planning. These results implicate the ventral specialization of sensorimotor cortex (including both precentral and postcentral gyri) for speech planning above and beyond motor execution.

[This corrects the article DOI: 10.3389/fmed.2023.1122529.].

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.

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.

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.

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.

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.