Thursday, June 6, 2019
Recap of the first day of the AANP annual meeting
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.