Neuropathology Blog Hits Million Pageview Mark!

I just noticed today that this blog now has more than one million pageviews since it inception in October 2007. And this marks the 856th post. Cheers!

Dr. Hilary Nickols: neuropathologist and artist

Hilary Nickols, MD, PhD

From time to time, I feature neuropathologists who exhibit talents beyond the strict confines of neuropathology. For example, I recently features the inimitable Mark Cohen and his prodigious classical guitar skills. I discovered another neuropathologist/artist during the recent annual meeting of the American Association of Neuropathologists:  Hilary Nickols, MD, PhD, of Norton Healthcare in Louisville, Kentucky. Dr. Nickols shared with me her detailed drawing of a craniotomy surgical field which she recently witnessed during a visit to the operating room.

The scene in the operating room, including drains, reflected dura, etc.

Recap of the final day of the AANP meeting

by Dr. Karra Jones:

The final day of the American Association of Neuropathologists annual meeting kicked off with our fearless leader, President Dr. Matthew Frosch.  Dr. Frosch entertained us with thought experiments related to our current methods of sampling tissue and their limitations.  He suggested that newer modalities developed by the following speakers will allow for interrogation of entire volumes of tissue drastically increasing our knowledge about the brain and disease. 

Dr. Kwanghun Chung from MIT talked about rapid 3D imaging and phenotyping of large-scale tissues.  He has developed highly innovative techniques to perform brain-wide molecular phenotyping by engineering the physiochemical properties of tissues, including clinical samples. His 3D image maps of the brain were beautiful and inspiring.   

The AANP Awards Ceremony was next with awards given out for the best platform/poster presentation in multiple categories, the international travel awards, and the Diagnostic Slide Session trainee awards with smiles all around. 

After a short coffee break, Dr. Ed Boyden from MIT talked about the development and use of expansion microscopy to image cells and biomolecules throughout the brain.  His multiplexed imaging techniques create colorful and highly informative images to study the brain and other tissues, and expansion microscopy can even be used on FFPE or fresh frozen tissue. You can find out more about his techniques and even read protocols at ExpansionMicroscopy.org. 

Dr. Jean Augustinack from Massachusetts General Hospital then talked about high-resolution ex vivo neuroimaging with histologic validation.  Her ex vivo images of brains showed amazing resolution and had a nice correlation with histologic sections.  Video of 7 Tesla MRI ex vivo images of a whole human brain at 100 micron resolution were amazing to see and the results were similar to what can be seen with the human eye during brain cutting. 

To finish the 95^th Annual Meeting of the American Association of Neuropathologists, Dr. Frosch installed the new officers, and Dr. Dan Brat, the incoming President, closed the meeting with a ceremonial tap of the gavel. 

It was an amazing and inspiring meeting, as usual.  Thanks to all the program organizers, committee members, our excellent AOE staff, and outgoing executive committee members for all of their hard work over the last year.  Next year in Monterey!

Recap of the third day of the AANP meeting

by J. Stephen Nix

The Saturday session of the 95th Annual Meeting of the AANP began with platform sessions on Alzheimer Disease and new technologies, highlighting cutting-edge developments in neuropathology research and techniques. The morning continued with the Korey lecture given by Dr. Jean Paul Vonsattel. Dr. Vonsattel delivered an insightful lecture on the investigation and mechanisms of hypokinetic and hyperkinetic disorders and the basal ganglia, including an in-depth review of relevant anatomy and history. Dr. Raymond Sobel was honored with a Meritorious Award presented by Dr. Jeffrey Golden for his innumerable contributions to neuropathology through his research, including neurodegeneration and immunology, as well as his service as Editor-in-Chief of JNEN and as the 2012 AANP president. Attendees then took advantage of free time to visit and discuss the many Saturday posters before attending the afternoon platforms on glioneuronal and non-glial tumors as well as trauma and forensics. The much-anticipated series “What Every Neuropathologist Needs to Know” did not disappoint with excellent lectures by Dr. Peter Pytel and Dr. Steve Moore. Dr. Pytel provided a practical, concise, and well-illustrated lecture on nerve pathology. Dr. Moore followed with an informative talk on muscle pathology, featuring live audience participation on the power of the H&E diagnosis. The interactivity of the Saturday AANP lectures, posters, and DSS session highlight the collegial environment of the AANP Annual meeting, one of the great benefit of the meeting for attendees and presenters alike.

Recap of the second day of the AANP meeting

The second day of the American Association of Neuropathologists annual meeting started with, of course, coffee. Our caffeinated brains were then further stimulated by the morning platform sessions (non-Alzheimer neurodegenerative and muscle/nerve running concurrently). Among the many excellent platform presentations was Lindsey Lowder's "Dementia in ALS: the role of the cerebellum". Dr. Lowder's work sheds light on the role of the cerebellum, an under-appreciated organ, in connecting ALS and cognitive dysfunction.

After the platform presentations, a second caffeine load was appreciated during the refreshment break. Then attendees convened to hear Beth Stevens, PhD of Boston Children's Hospital deliver the Parisi Lecture. Dr. Stevens presentation, entitled Microglia Function and Dysfunction in Neurologic Disease, described the role of microglia in synapse pruning. Although a normal part of neurologic development, there is evidence that it can be aberrantly reactivated in Alzheimer's disease. Further understanding of this microglial function in normal aging and in disease may lead, according to Dr. Stevens, to the identification of new biomarkers and therapeutic targets.

Eileen Bigio, MD

Morning activities came to a close with the Award for Meritorious Contributions to Neuropathology bestowed upon the illustrious Eileen Bigio, MD. In addition to her pioneering work in frontotemporal lobar degeneration, Dr. Bigio was recognized for her teaching talent and for her service to the profession. As Dr. Qinwen Mao said, Dr. Bigio "has the mysterious ability to present complicated concepts in a simple, clear, and humorous way." Her contribution to the AANP has included service on the Program Committee, the Awards Committee, and the Executive Committee. In 2020, she will become Vice President of the AANP.

After the organizational business meeting, the lunch break allowed time for those who wanted to preview slides for tomorrow's diagnostic slide session to retire to the microscopic viewing room to go over glass slides. A triple-headed microscope allowed for lively discussions of challenging cases among colleagues. The afternoon break was also time for the trainee luncheon, a meeting highlight for residents and fellows looking for advice on future employment in the field of neuropathology

The afternoon platform sessions then ensued (glial tumors concurrent with developmental/pediatric/infectious disease). Time for poster viewing over yet more coffee was then allowed. I counted 234 posters at this year's meeting. The day ended with the Dearmond Lecture, given by Dr. Alison Goate, entitled Rare and Common Genetic Variation Implicate Microglial Function in Alzheimer's Disease Risk.

Oblivious to the gray and rainy conditions outside in Atlanta, participants at Day #2 of the 95th annual meeting all seemed to have a wonderful time learning about hot-off-the-press discoveries in the field, making new connections with colleagues, and reaffirming lifelong associations with old friends.

Recap of the first day of the AANP annual meeting

Dr. Maria Martinez-Lage was kind enough to write the following summary of events at today’s American Association of Neuropathologists meeting in Atlanta:

The opening day of the 95th Annual Meeting of the American Association of Neuropathologists in Atlanta featured a special course dedicated to a topic both old and new: what happens when treatments go awry? Under the title “Unintended Consequences: The Iatrogenic Neuropathology of Systemic Therapies” the faculty discussed neurologic adverse effects of novel immunotherapies,other cancer and non-cancer related treatments, and aspects of immunotherapy and the gut microbiome in Alzheimer’s Disease. 

Novel immunotherapies bring novel complications

The early morning talks introduced basic concepts and historical notes on cancer immunotherapy. Dr. Dietrich and Dr. Gust, two expert neurologists, explained the intricacies of novel cellular therapies used in hematopoietic malignancies, specifically chimeric antigen receptor T cells (CAR-T) directed against CD19, and their neurotoxic effects. After an excellent introduction, several clinicopathological cases were described to illustrate the characteristics of Immune-effector Cell Associated Neurotoxicity Syndrome (ICANS) and the potential underlying pathophysiological mechanisms, including cytokine release and neurovascular unit injury . While treatment with CAR-T cells is still limited to a handful of centers worldwide, the use of immune checkpoint inhibitors in advanced stage malignancies has increased exponentially in the last decade. Dr. Martinez-Lage reviewed the mechanisms of action of these T-cell stimulating drugs, and the clinical and neuropathological characteristics of neurological immune-related adverse events (irAE). 

Glial dysregulation and T-cell activation mediate CNS injury 

Dr. Vogel reviewed aspects of cancer therapy-induced leukoencephalopathy (such as methotrexate induced necrotizingleukoencephalopathy), and beautifully illustrated recent data indicating that chemotherapy-induced white matter injury(“chemobrain”) is mediated by dysregulation of oligodendroglial progenitor cells, astrocytes, and microglia. Another neurotoxic effect from a number of systemic therapies is T-cell encephalitis, and Dr. Nath proficiently discussed underlying mechanisms , some shared with immune-reconstitution syndrome, including direct neuronal toxicity by T-cells through pathways unrelated to classic cellular lysis.

Alzheimer’s disease (AD), immunotherapy, the microbiome, and neuromuscular system vulnerabilities

Immunization against beta-amyloid has been used as a strategy in AD, and long term follow up of patients from early trials by Dr. Nicoll shows that although amyloid plaques can be successfully removed, the progression of cognitive decline is not altered. We alsolearned from Dr. Bendlin about studies demonstrating differences in the gut microbiome between patients with AD and controls, arising questions about the intriguing potential role of the gut-brain axis in AD. An incredibly practical case-based review on therapy-related neuromuscular disease by Dr. Jones closed the course, with many attendees actively taking notes even after a full day of learning!

The first day of the 95th Annual Meeting of the AANP was a great success with an outstanding lineup of speakers bringing to our attention practical aspects of novel and some better known systemic therapies and their effects in the nervous system.  The reception that followed was equally well attended despite a last minute change of venue due to weather conditions.

American Association of Neuropathologists annual meeting gets underway

I arrived in Atlanta this afternoon in anticipation of tomorrow's kick-off of the American Association of Neuropathologists annual meeting. I've already run into a number of neuropathologists from around the country, including: Howard Chang, William Taylor, Eddie Lee, Beatriz Lopes, Roberta Seidman, Doug Miller, Mary Fowkes, Clare Bryce, Ray Sobel, Tessa Hedley-White, and Leroy Sharer. Looking forward to a great meeting!

I caught up with the inimitable Dr. Leroy Sharer (right) while checking in for the meeting