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76th Annual Meeting of the American Academy of Neurology

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With an attendance of approximately 11,000 people in person and 3000 virtually, the 76th Annual meeting of the American Academy of Neurology (AAN) in Denver was again the primer event for neurologists worldwide. The AAN meeting had a traditional format with plenary sessions posters and oral presentations. As in the past, many informal sessions, small gatherings and interest groups dotted the large Denver Convention Center. Satellite meetings focused on diverse topics like trainee networking, academic careers, private practice and policy, leadership, research, brain wellness, emerging science and education aimed at neurologists at different stages in their careers.

The Meeting was an ideal setting to explore one’s own area of interest as well learn what is new in other fields of neuroscience. For example, in Parkinson disease there was further confirmation of the role of the environment in the form of pesticides and the growing number of Parkinson cases. New therapeutic interventions were reported like focused-ultrasound to the globus pallidus to reduce tremor, sub cutis levo-dopa and the promise of an FDA phase 2 study with prasinezumab, a monoclonal antibody that prevents aggregation of α-synuclein in the early stages of the disease. 

Novel approaches were reported in vascular and neurodegenerative disease explored from a neuro-immunological point of view, potentially opening new therapeutic pathways. These approaches can give us a sense of the future and blur the traditional boundaries between degenerative and inflammatory disease. 

In the neuromuscular areas myasthenia and inflammatory polyradiculoneuropathy are benefitting from similar neuro-immunological approaches with additional analyses reported on rozanolixizumab-noli and efgartigimod respectively which promise soon to benefit our patients.  

In multiple sclerosis well established drugs like ocrelizumab and ofatumumab appear to maintain their safety profile over 5-10 years since approval. The drug trials plenary session addressed newer pharmacological intervention under development in diverse conditions from agitation in Alzheimer disease, glioma, Niemann-Pick disease, and HSV encephalitis, to middle cerebral artery embolization in the treatment of subdural hematomas.

Beyond the topics focused on single diseases, a main theme is emerging at the AAN: Brain Health. Weaving brain health into our clinical practice is becoming a reality. Often the patients themselves or their family members open the discussion on healthy brain practices. The AAN mission has changed to include brain health as one of their main pillars:“ …to improve overall neurologic health and quality of life for all people through unparalleled lifelong education, quality improvement, scientific discovery, effective therapies, and optimizing brain health.”  The concept of preventative neurology is emerging through the encouragement of a healthy lifestyle by focusing on physical activity, mental exercise, healthy diet and nutrition, social interaction, ample sleep and relaxation, and control of vascular risk factors. Sanjay Gupta MD, a keynote speaker during a plenary session discussed this approach by suggesting putting the accent on the positive, not telling what to do so that things stay the same, but rather emphasizing what one could do if health is maintained through life. Afterall, we age the same way we have lived our lives.

As a behavioral neurologist I cannot omit reporting on the studies reported of the newly anti-βamyloid monoclonal antibodies, lacanemab and soon likely, donanemab.  While the data available from the studies which lead to the FDA approval show a modest clinical benefit over 18 months similar to donepezil and potential for brain swelling and hemorrhage, the discussion in several session revolved around the clinical application of this new class of drugs to the “real world neurology”. Strategies on how to avoid vascular complication by careful patient selection, the assessment of genetic risks in APOE4 carriers, proof of positive βamyloid biomarkers by CSF or PET, the required close infusion and MRI monitoring, the need for financial counseling due to the anticipated high out of pocket cost for the patient, are necessary components which seem to suggest that only specialized centers will  have the infrastructure needed to administer these new class of drugs. This implies waiting lists estimated to be close to a year and relatively small number of eligible patients as a study from the Mayo Clinic Aging Study seem to suggest.

Plasma biomarkers measuring βamyloid and tau protein have come a long way. They are strongly correlated to brain levels of PET βamyloid and Tau and used to screen drug study candidates. But their use in clinical practice may not be simple.  Dr. Michelle Mielke from Wake Forest University, reported that MI, stroke chronic renal failure and other clinical variables can skew biomarkers level.  

Because of the long preclinical stage of Alzheimer disease, plasma biomarkers can be positive in a cognitive intact individual. This begs the question: should cognitively normal subjects with positive biomarkers be diagnosed having Alzheimer? Not an easy answer, but we will hear more on this at the 77th AAN Meeting in San Diego next year.

Dr. Antuono reports no conflicts of interest.

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