Faculty Bibliography

OBJECTIVES/OBJECTIVE:Anti-amyloid-beta immunotherapy requires frequent MRI screening for amyloid-related imaging abnormalities-hemorrhage subtype (ARIA-H), consisting of cerebral microbleeds (CMB) and/or superficial siderosis (SS), using gradient-recalled echo (GRE) or susceptibility-weighted imaging (SWI). Screening MRI sequences for ARIA-H may benefit from acceleration to maximize patient enrollment by increased throughput and reduced motion degradation. This study assessed the diagnostic performance of standard GRE and SWI to echo-planar imaging (EPI) accelerated substitutions for detecting CMB and SS. MATERIALS AND METHODS/METHODS:This retrospective single-center rater study included 50 patients, 25 with CMB and 25 patients without CMB (median age 77 y, IQR: 70 to 82 y; 30 of 50 female) who were imaged with FDG PET-3T MRI from April to July 2023. Standard GRE (90 s) and SWI (192 s) were compared with an EPI-accelerated GRE (aGRE; 13 s, 86% time reduction) and an EPI-accelerated SWI substitution (aSWI; 33 s, 83% time reduction). Three board-certified neuroradiologists independently reported CMB and SS (per ARIA-H monitoring guidelines), perceived image quality and motion for each sequence. There were 240 total assessments per rater (the 4 different sequences for the 50 patients plus 10 duplicated patients). Sensitivity, specificity, positive and negative predictive values, area under the curve (AUC), inter-rater and intrarater agreement were determined for each sequence and rater. RESULTS:The aggregate AUCs for the 4 individual sequences were excellent for detecting CMB (0.84 to 0.94) and SS (0.89 to 1.00) without statistical differences observed between standard and EPI-accelerated substitutions. Both aGRE and aSWI had high negative predictive values (96.5% to 100%). There were modest quantitative correlations between standard and accelerated sequences (0.606 and 0.391 for GRE and SWI, respectively), no differences in CMB count for aGRE (bias 0.01, P=0.895), but reduced CMB count with aSWI (bias -1.12, P=0.014). Inter-rater agreements were mildly reduced for both GRE versus aGRE (eg, 0.757 to 0.622 for CMB detection) and SWI versus aSWI (eg, 0.834 to 0.649 for SS detection). Perceived image quality for accelerated sequences was reduced, but with less motion observed with aSWI. CONCLUSIONS:The aGRE and aSWI sequences shorten scan times 86% and 83%, respectively, with similar diagnostic performance for ARIA-H screening, but reduced rater agreement and perceived image quality.

Facial nerve palsy is a debilitating condition with substantial physical and psychosocial impacts. Facial reanimation encompasses surgical reconstructive procedures aimed at restoring the functions of the facial nerve to improve function and quality of life in patients with facial palsy. This educational review outlines the essential principles for interpreting imaging studies for facial reanimation including fundamental anatomy, technical descriptions and imaging appearances of common reconstructive procedures, and key findings that should be included when reporting studies for patients being considered for facial reanimation. The information provided in this review equips radiologists to contribute effectively to a multidisciplinary team necessary for the treatment of patients with facial nerve palsy.

BACKGROUND:Genetically engineered porcine livers are being developed as a bridge therapy for acute liver failure, providing detoxification and restoration of hepatic protein synthesis. Severe xenograft-associated severe thrombocytopenia remains a major limitation, and human mechanistic data are scarce. METHODS:Platelet kinetics were characterized in three human decedents undergoing extracorporeal cross-circulation with transgenic porcine livers. Platelet counts, transfusion requirements, and clearance patterns were assessed to distinguish consumption from marrow suppression or hypersplenism. Antibody- and complement-directed inhibitors were administered to test immune-mediated mechanisms. Mechanistic studies focused on porcine von Willebrand factor (pVWF)-dependent platelet activation, including ex vivo blockade with the anti-VWF nanobody caplacizumab, a vWF-directed antibody fragment that prevents vWF-platelet binding. A fourth decedent received caplacizumab during porcine liver perfusion. RESULTS:In all three initial cases, 80%-90% of circulating and transfused platelets were rapidly cleared, a pattern inconsistent with marrow suppression or hypersplenism. Antibody and complement inhibition failed to ameliorate thrombocytopenia. Recipient plasma induced robust pVWF-mediated platelet activation analogous to human Type IIb von Willebrand disease, which was completely abrogated ex vivo by caplacizumab. In a fourth decedent treated with caplacizumab, aberrant platelet activation was prevented, though full hematologic recovery was limited by pre-existing disseminated intravascular coagulation (DIC). CONCLUSIONS:Early thrombocytopenia during porcine liver xenotransplantation appears to be primarily driven by pVWF-mediated platelet activation rather than by classical immune or splenic mechanisms. Targeted VWF blockade with agents such as caplacizumab may mitigate platelet loss and improve the safety profile of extracorporeal porcine liver support in acute liver failure.

TDP-43 is an RNA and DNA binding protein that plays major roles in regulating RNA processing. In particular, TDP-43 dysfunction leads to the accumulation of cryptic splice isoforms that result from improperly spliced mRNAs. In addition to its role in regulating splicing, TDP-43 is also known to regulate the expression of transposable elements (TEs). TEs are mobile genetic elements which comprise a significant proportion of the human genome, but are normally silenced in healthy somatic cells. TEs are interspersed throughout the genome, both in gene-depleted regions and within gene introns and gene regulatory sequences. We used optimized long-read RNA sequencing assays to generate catalogs of mis-spliced and mis-expressed genes and TEs in human neurons depleted for TDP-43. In addition to known TDP-43 driven cryptic isoforms, we identified hundreds of TDP-43 dependent spliced RNAs that form cryptic gene-TE fusion events as a result of mis-splicing of TE sequences into gene transcripts. Among these TDP-43 dependent cryptic gene-TE transcripts (crypTEs), we found: TEs that provide alternate gene promoters/5'UTRs, TEs that act as cassette exons inside host gene mRNAs, as well as TEs that provide alternate transcript 3' ends. These cryptic gene-TE fusions are predicted to induce aberrant expression of ALS relevant genes, nonsense mediated decay (NMD) products, as well as novel peptides from gene-TE fusions within the gene coding sequence. Using coupled long-read RNA (Iso-seq) and single-nucleus (snRNA-seq) profiles from postmortem ALS tissues, we further verified that many of these crypTE transcripts are enriched in frontal cortex samples from ALS donors with cognitive involvement (ALSci) and associated with altered expression of those genes in deep layer cortical excitatory neurons. In short, TDP-43 dependent crypTEs greatly expand the catalogs of TDP-43 dependent cryptic splice isoforms and represent a novel mechanism by which TE dysregulation impacts ALS.

BACKGROUND:Sexual health counseling (SHC) is a critical aspect of inflammatory bowel disease (IBD) care. Less is known about sexual health counseling in patients who identify as members of a sexual or gender minority (SGM) group. AIMS/OBJECTIVE:This study aims to characterize patient-reported sexual health counseling in SGM vs. non-SGM patients with IBD. METHODS:We conducted an anonymous, cross-sectional survey of patients over 18 years old with IBD, currently receiving care at a large, tertiary care IBD center. Data collection included demographics, IBD history, and patient recall of SHC. Patients who self-identified as SGM were compared to non-SGM patients, with subgroup analyses by sex assigned at birth. Means were compared using t tests and percentages compared using chi-square analysis. RESULTS:A total of 162 patients (41 SGM and 121 non-SGM) completed the survey. Both groups reported IBD impacted their sexual practices (ranging from 44% non-SGM men to 64% SGM women). SGM patients were more likely to report that their gastroenterologist asked about sexual health compared to non-SGM patients (p < .005). Importantly, 31% of respondents reported seeking SHC from their gastroenterologist (GI), placing GIs among the top sources of information regarding sexual health in this cohort. CONCLUSION/CONCLUSIONS:Most study participants reported that IBD has impacted their sexual practices. SHC rates were low in all study groups despite GI providers being a primary source of information. Clearer recommendations on aspects of SHC could improve quality of care for both SGM and non-SGM patients with IBD.

This study investigates associations between the strength of local Tobacco Retail Licensing (TRL) laws and adult tobacco use patterns (i.e., cigarette, e-cigarette, and dual use), and differences by sociodemographic characteristics, using California as a case study. We merged data from the American Lung Association's (ALA) State of Tobacco Control Reports and the California Health Interview Survey (CHIS) from 2016 to 2022. We recoded the ALA local policy grades as strongest (highest grade) versus weaker (all other grades). Using quantitative methods, we estimated multilevel multinomial logistic regression models to examine the relationship between the strength of local TRL laws and cigarette and e-cigarette single and dual use among adults aged 25 and older, nesting by city/town. We also examined the potential for effect modification by including interaction terms for race and ethnicity, income, and education in separate models. Our results showed that no associations existed between stronger TRL grades and exclusive cigarette, e-cigarette or dual use in any of the models. Neither were there statistically significant interactions by race and ethnicity, income, or education. These null findings suggest that while TRL laws may potentially be useful to restrict adolescent access, local TRL strength may have few impacts on adult nicotine consumption.

The convergence of artificial intelligence (AI) and neuroscience represents one of medicine's most profound intellectual partnerships. Neuronal architecture has inspired computational methods, while computational models, evolving from theoretical constructs to transformative clinical tools, are reshaping neurological practice. As AI systems attempt to augment diagnostic accuracy, treatment planning, and patient care, neurologists must develop fluency in these technologies to harness their potential while navigating their limitations and dangers. AI-related publications have exponentially increased in recent years, yet many neurologists lack the foundational computer science background needed to critically evaluate and most safely and effectively implement these tools in clinical practice. This article serves to outline the historical foundations linking neuroscience to computing, examine core concepts of the past and current AI landscape in neurology, and describe methodologies that aim to revolutionize neurological care.

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Although patients with FL have high response rates to therapy, most develop increasingly resistant disease. In addition, transformation into an aggressive lymphoma is associated with unfavorable outcomes. Many novel agents are under investigation, and early clinical data are encouraging. Aligning treatment with the underlying tumor biology and sequencing of therapies remain key clinical challenges. At the Lymphoma Research Foundation's biannual 2024 Follicular Lymphoma Scientific Workshop, experts convened to discuss the role of chemotherapy in the context of new therapies, the impact of early progression on treatment sequencing, novel end points in clinical trials, disease biology and the tumor microenvironment, and new treatments on the horizon. This report focuses on updates in FL biology, first-line treatment, the role of progression of disease in 24 months, clinical trial design, and redefining cure in FL.

PURPOSE OF REVIEW/OBJECTIVE:This review discusses the current state of the evidence related to the relationship between the cerebellum and epilepsy, highlighting evidence on neurostimulation of the cerebellum for treatment of epilepsy, and placing current knowledge into historical context. RECENT FINDINGS/RESULTS:The cerebellum plays an important role in certain epilepsy types, both as a key part of epileptic networks and an area that can give rise to seizures. Cerebellar stimulation as a potential treatment for drug-resistant epilepsy is a recurring, albeit niche, topic of interest. Over decades of intermittent, often highly limited investigations into this area of research, there are still more questions than answers. However, more recent preclinical insights point the way towards leveraging modern surgical techniques and technology in investigating cerebellar stimulation as a potential viable treatment approach to select types of epilepsy. SUMMARY/CONCLUSIONS:Cerebellar stimulation holds promise for improving seizure control in people with specific types of drug-resistant epilepsy. Future studies should leverage new preclinical data, along with modern technology, neurosurgical techniques, and clinical trial design, to help determine the optimal stimulation parameters, optimal stimulation targets, and optimal patient-selection for this promising area of investigation.

Chromosomal rearrangements on the short arm of Chromosome 8 cause 8p syndrome, a rare developmental disorder characterized by neurodevelopmental delays, epilepsy, and cardiac abnormalities. Although significant progress has been made in managing the symptoms of 8p syndrome and other conditions caused by large-scale chromosomal aneuploidies, no therapeutic approach has yet been demonstrated to target the underlying disease-causing chromosome. Here, we establish a two-step approach to eliminate the abnormal copy of Chromosome 8 and restore euploidy in cells derived from an individual with a complex rearrangement of Chromosome 8p. Transcriptomic analysis revealed 361 differentially expressed genes between the proband and the euploid revertant, highlighting genes both within and outside the 8p region that may contribute to 8p syndrome pathology. Furthermore, we demonstrate that the proband exhibits a significant defect in neural differentiation that could be partially rescued by treatment with small-molecule inhibitors of cell death. Our work demonstrates the feasibility of using chromosome engineering to correct complex aneuploidies in vitro and establishes a platform to further dissect the pathophysiology of 8p syndrome and other conditions caused by chromosomal rearrangements.