Thank you

This live web event has ended. Thank you for attending.

Description

Platform Presentations
Please see the Resources tab for full abstracts and co-authors.

Platform 5: Neurodegenerative: Other
Moderators: Michael Miller, MD, PhD and Brittany Dugger, PhD
8:00 am – 8:15 am
33. Multi-OMIC analysis of Huntington disease reveals a neuroprotective astrocyte state

• Osama Al-Dalahmah, MD, PhD

8:15 am – 8:30 am
34. Chronic Traumatic Encephalopathy in a Cohort of Military Veterans in the UNITE Brain Bank

• Ann McKee, MD

8:30 am – 8:45 am
35. Deciphering the role of the NBIA-mutated protein WDR45 in autophagy and neuroprotection

• Rajnish Bharadwaj, MD, PhD

8:45 am – 9:00 am
36. The New Brunswick Neurological Syndrome of Unknown Cause (NSUC) -- evidence of a fake

• Gerard Jansen

9:00 am – 9:15 am
37. Efficacy of Routine Scout Sections in the Diagnosis of Spongiform Encephalopathies

• Jacob A. Houpt, MD

9:15 am – 9:30 am
38. Differing cognitive profiles in limbic-predominant age-related TDP-43 encephalopathy, frontotemporal lobar dementia, and Alzheimer disease

• Satomi Hiya

9:30 am – 9:45 am
39. Brain Digital Slide Archive (BDSA): An Open Source Whole Slide Image Sharing Platform for AD/ADRD Research and Diagnostics

• Margaret Flanagan, MD

9:45 am – 10:00 am
40. Pathologically Based Criteria to Distinguish Essential Tremor from Controls: Analyses of the Human Cerebellum

• Phyllis Faust, MD, PhD

Platform 7: Developmental/Pediatric
Moderators: Karra Jones, MD, PhD and Angela Viaene, MD, PhD

2:00 pm – 2:15 pm
49. Building a gene expression atlas of developing brainstem motor neurons to study rare congenital neurologic disorders

• Nima Shirooni

2:15 pm – 2:30 pm
50. Disrupted rhombic lip developmental in medulloblastoma oncogenesis: Taking another look at cerebellar dysplasia & heterotopia

• Melissa Blessing, DO

2:30 am – 2:45 pm
51. Autopsy-Based Insights into Pediatric Nontraumatic Intracranial Hemorrhage: A Ten-Year Retrospective Review

• Jolee Suddock, DO

2:45 pm – 3:00 pm
52. Biomechanical Contributions of Tensegrity in the Formation of Polymicrogyria

• Jacob A. Houpt, MD

3:00 pm  – 3:15 pm
53. Frequent Cerebral Intraparenchymal Calcification in Cases of Sudden Unexplained Death in Pediatrics

• Alicia Sandoval, MD

3:15 pm – 3:30 pm
54. Congenital Moebius Syndrome Shows Primary Abducens Motor Nuclei Lesion, Secondary Facial Neuron Loss, and Abnormal Tracts

• Sarai Santos, MD, PhD

3:30 pm – 3:45 pm
55. Keratan Sulfate: Chemical Template for Neuroblast Migratory Pathways and Axonal Fascicles

• Harvey Sarnat, MS, MD, FRCPC

3:45 pm – 4:00 pm
56. Multimodal high-resolution whole-brain characterization of holoprosencephaly (HPE) from 13-22 gestational weeks

• Richa Verma

Korey Lecture:
Why the Microscope Still Matters
Craig Horbinski, MD, PhD
Northwestern University, Chicago, IL

Biography
Dr. Horbinski hails from Buffalo, NY, where he completed his combined M.D., Ph.D. training at the State University of New York at Buffalo. He then did an Anatomic Pathology residency and a Neuropathology fellowship at the University of Pittsburgh. As a tenured professor at Northwestern University, Dr. Horbinski directs the Neuropathology Division, the Nervous System Tumor Bank, and the Lurie Comprehensive Cancer Center Pathology Core Facility. Dr. Horbinski’s clinical specialty is molecular diagnostics of brain tumors. To date, Dr. Horbinski has authored over 230 peer-reviewed publications and has obtained extramural research support as a principal investigator from multiple sources, including the NIH and American Brain Tumor Assocaition. His NCI SPORE-funded brain tumor bank has supported over 100 intramural and extramural research projects. He has delivered over 120 invited talks and platform presentations at a variety of national and international settings. Dr. Horbinski is an Associate Editor of Neuro Oncology and Neuro Oncology Advances, and is on the editorial board of Acta Neuropathologica, Brain Pathology, and the Journal of Neuropathology and Experimental Neurology. In 2024 Dr. Horbinski was inducted into the American Society for Clinical Investigation.

Learning Objectives
1. Summarize the major technological advances in molecular diagnostics over the past two decades
2. Describe how molecular testing should be integrated into the routine neuropathologic workup of CNS tumors
3. Explain why molecular diagnostics can only augment, not replace, light microscopic examination for clinical diagnosis and research

Abstract
Silicon Valley and venture capitalists often categorize new technologies as “painkillers” (make tedious jobs easier) and/or as “vitamins” (enhance the user’s powers). Molecular diagnostics are technologies that have advanced so much over the past two decades that their utilization is now standard-of-care for the workup of central nervous system tumors. Their ability to resolve cases that are challenging by traditional histopathologic approaches has led many treating physicians, and even some pathologists, to conclude that the microscope is becoming obsolete. In this session, we will survey the field of molecular diagnostics, use case-based examples of how to integrate molecular data into surgical neuropathology, and discuss some reasons why histopathology will remain the cornerstone of CNS tumor evaluation for the foreseeable future. The central objective is to convince listeners that, when used properly, advanced molecular diagnostics are both vitamins AND painkillers, not job-killers.

References
1. Capper D et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018 Mar 22;555(7697):469-474. PMID: 29539639.
2. Horbinski C et al. NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022. J Natl Compr Canc Netw. 2023 Jan;21(1):12-20. PMID: 36634606.
3. Horbinski C et al. The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients. Neuro Oncol. 2019 Dec 17;21(12):1498-1508. PMID: 31276167.
4. Louis DN et al. Announcing cIMPACT-NOW: the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy. Acta Neuropathol 2017 Jan;133(1):1-3. PMID: 27909809.
5. Louis DN et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-1251. PMID: 34185076.


What Every Neuropathologist Needs to Know: Update on NeuroID Workups, Consultation Resources
Isaac Solomon, MD, PhD
Brigham and Women's Hospital, Boston, MA

Biography
Dr. Solomon is an assistant professor of pathology at Harvard Medical School and a neuropathologist at Brigham and Women’s Hospital where he also serves as an associate medical director of the clinical microbiology laboratory, the associate program director of the Franz von Lichtenberg infectious disease and molecular microbiology fellowship, and as an infectious disease pathology consultant. Prior to his current position, he graduated from the Medical Scientist Training Program at Washington University in St. Louis with a doctoral dissertation on prion pathogenesis, and then completed anatomic pathology residency, medical microbiology fellowship, and neuropathology fellowship training at Brigham and Women’s Hospital and Boston Children’s Hospital. His primary research interests are centered on the diagnosis and pathogenesis of CNS viral infections, including SARS-CoV-2, HIV, and arbovirus encephalitis. He currently serves as the president of the Binford-Dammin Society of Infectious Disease Pathologists, and has recently published the 3rd edition of Diagnostic Pathology: Infectious Diseases.

Learning Objectives
1. Generate an infectious differential diagnosis based on inflammatory patterns and clinical history
2. Select appropriate stains and molecular assays to confirm an infectious etiology
3. Integrate molecular test results with histological findings for a final diagnosis

Abstract
Infections of the central nervous system cause significant morbidity and mortality, and are frequently encountered in surgical and autopsy pathology. A wide variety of microorganisms can infect the CNS including bacteria, fungi, viruses, and parasites, and efficient diagnosis is necessary to initiate appropriate therapy within a clinically impactful timeframe. Most infections are associated with characteristic inflammatory patterns, which can be used to form an initial differential diagnosis, and confirmed with appropriate special stains, immunohistochemistry, and molecular testing. Final integrated diagnoses require careful interpretation of histological, molecular, microbiology cultures, and other laboratory testing results within the context of the individual patient’s immune status and exposure history. Consultation with local experts in microbiology and infectious disease pathology can be helpful in guiding workup and interpreting testing results. Public health and national reference laboratories can be utilized to diagnose rare or emerging infections and in outbreak investigations.

References
1. Molecular and Histologic Diagnosis of Central Nervous System Infections. Solomon IH. Surg Pathol Clin. 2020 Jun;13(2):277-289. PMID: 32389267
2. Diagnostic Testing in Central Nervous System Infection. Kanjilal S, Cho TA, Piantadosi A. Semin Neurol. 2019 Jun;39(3):297-311. PMID: 31378866
3. Viral meningitis and encephalitis: an update. Gundamraj V, Hasbun R. Curr Opin Infect Dis. 2023 Jun 1;36(3):177-185. PMID: 37093042
4. Progress and Challenges in Bacterial Meningitis: A Review. Hasbun R. JAMA. 2022 Dec 6;328(21):2147-2154. PMID: 36472590
5. Epidemiology, clinical presentation, and predictors of outcome in nontuberculous mycobacterial central nervous system infection: a systematic review. Meena DS, Kumar D, Meena V, Bohra GK, Tak V, Garg MK. Trop Med Health. 2023 Sep 25;51(1):54. PMID: 37749661
6. Histopathologic diagnosis of fungal infections in the 21st century. Guarner J, Brandt ME. Clin Microbiol Rev. 2011 Apr;24(2):247-80. PMID: 21482725
7. The Landscape of Parasitic Infections in the United States. Mathison BA, Pritt BS. Mod Pathol. 2023 Aug;36(8):100217. PMID: 37182583
8. Helminthic Infections of the Central Nervous System. Cho TA. Continuum (Minneap Minn). 2018 Oct;24(5, Neuroinfectious Disease):1489-1511. PMID: 30273249

What Every Neuropathologist Needs to Know: AI in Diagnostic and Research Neuropathology
John Crary, MD, PhD
Mount Sinai Medical Center, New York, NY

Biography
John F. Crary, MD, PhD, is a Professor of Pathology, Neuroscience, and Artificial Intelligence & Human Health at the Icahn School of Medicine at Mount Sinai where he was the founding director of the Neuropathology Brain Bank & Research CoRE. Dr. Crary has made substantial contributions to approaches to diagnostic categorization of several neurodegenerative diseases, leading the effort to delineate primary age-related tauopathy (PART) and others. Dr. Crary is a pioneer in applying deep learning to addressing neurodegenerative disease. Dr. Crary’s laboratory was the first to apply convolutional neural networks to Alzheimer’s neuropathology. In addition, the Crary laboratory developed an AI capable of detecting synucleinopathy in peripheral biopsies, which has the potential to rapidly accelerate the pace of clinical trials. The Crary laboratory developed a powerful algorithm, termed “HistoAge” which is a novel approach to studying brain age-acceleration and neurodegeneration. Further, the Crary laboratory has demonstrated that neural networks can extract essentially limitless numbers of features related to the brain in an unbiased way and train on them, learning the most relevant cellular abnormalities for a given symptom or disease. Currently, the Crary laboratory is training AI models that can perform complex neuroanatomical segmentation on the cellular level, and others that measure brain age acceleration, neurodegeneration, and functional impairment.

Learning Objectives
1. Describe the primary applications of artificial intelligence in neuropathology
2. Describe the benefits and limitations of using AI in neuropathology
3. Gain insights into the future directions of AI in neuropathology and how it may shape the field in the coming years.

Abstract
This lecture explores the transformative role of artificial intelligence (AI) in neuropathology, focusing on diagnostic and research applications. As neuropathology becomes increasingly complex, AI offers promising tools to enhance diagnostic accuracy, efficiency, and depth of analysis. This lecture will delve into several key areas where AI is making significant impacts, including digital pathology, natural language processing, and advanced machine learning techniques such as foundation models and multiple instance learning. Participants will be introduced to cutting-edge studies and developments. Further, the lecture will discuss the practical implications of implementing AI tools in everyday neuropathological workflow, examining both the infrastructure required and the potential barriers in typical clinical settings. By examining these topics, the lecture aims to equip neuropathologists with the knowledge to critically assess AI technologies, understand their applications and limitations, and consider the future of AI in enhancing the neuropathological research and diagnostic landscape.

References
1. Scalco R, Hamsafar Y, White CL, Schneider JA, Reichard RR, Prokop S, Perrin RJ, Nelson PT, Mooney S, Lieberman AP, Kukull WA, Kofler J, Keene CD, Kapasi A, Irwin DJ, Gutman DA, Flanagan ME, Crary JF, Chan KC, Murray ME, Dugger BN. The status of digital pathology and associated infrastructure within Alzheimer's Disease Centers. J Neuropathol Exp Neurol. 2023 Feb 21;82(3):202-211. doi: 10.1093/jnen/nlac127. PMID: 36692179; PMCID: PMC9941826.
2. Vizcarra JC, Pearce TM, Dugger BN, Keiser MJ, Gearing M, Crary JF, Kiely EJ, Morris M, White B, Glass JD, Farrell K, Gutman DA. Toward a generalizable machine learning workflow for neurodegenerative disease staging with focus on neurofibrillary tangles. Acta Neuropathol Commun. 2023 Dec 18;11(1):202. doi: 10.1186/s40478-023-01691-x. PMID: 38110981; PMCID: PMC10726581. https://pubmed.ncbi.nlm.nih.gov/38110981/
3. Marx GA, Kauffman J, McKenzie AT, Koenigsberg DG, McMillan CT, Morgello S, Karlovich E, Insausti R, Richardson TE, Walker JM, White CL 3rd, Babrowicz BM, Shen L, McKee AC, Stein TD; PART Working Group; Farrell K, Crary JF. Histopathologic brain age estimation via multiple instance learning. Acta Neuropathol. 2023 Dec;146(6):785-802. doi: 10.1007/s00401-023-02636-3. Epub 2023 Oct 10. PMID: 37815677; PMCID: PMC10627911. https://pubmed.ncbi.nlm.nih.gov/37815677/
4. Huang Z, Bianchi F, Yuksekgonul M, Montine TJ, Zou J. A visual-language foundation model for pathology image analysis using medical Twitter. Nat Med. 2023 Sep;29(9):2307-2316. doi: 10.1038/s41591-023-02504-3. Epub 2023 Aug 17. PMID: 37592105.
5. Vogelgsang J, Dan S, Lally AP, Chatigny M, Vempati S, Abston J, Durning PT, Oakley DH, McCoy TH, Klengel T, Berretta S. Dimensional clinical phenotyping using post-mortem brain donor medical records: post-mortem RDoC profiling is associated with Alzheimer's disease neuropathology. Alzheimers Dement (Amst). 2023 Sep 22;15(3):e12464. doi: 10.1002/dad2.12464. PMID: 37745891; PMCID: PMC10517223.


Diagnostic Slide Session
Diagnostic Slide Session Moderator: Caterina Giannini, MD, PhD
Diagnostic Slide Session Manager: Kathy Newell, MD
Case 1
DSS Presenter: Julieann C. Lee, MD

Case 2
DSS Presenter: Sharika Rajan, MD

Case 3
DSS Presenter: Blake Ebner, MD, PhD

Case 4
DSS Presenter: Sophia Zhang, DO

Case 5
DSS Presenter: Gabriel Sexton, MD

Case 6
DSS Presenter: Nicolas Kostelecky, MD

Case 7
DSS Presenter: Jane E. Persons, MD, PhD

Case 8
DSS Presenter: Merryl Terry, MD

Case 9
DSS Presenter: Marwan Majeed, MD, MPH

Case 10
DSS Presenter: Liana Kozanno, MD, PhD

Case 11
DSS Presenter: Katelyn E. Moss, DO

DSS 2024 Learning Objectives
1. Describe advancements in diagnostic criteria and techniques for diseases of the central nervous system.
2. Apply diagnostic criteria to develop differential diagnoses.
3. Recognize the underlying causes of diseases of the central nervous system.