Undiagnosed Neurological Diseases: The Challenge of Atypical Clinical Presentations*
Date: October 19, 2026
Time: 12:00 pm to 1:00 pm
Room: Seaglass
Track: Interactive Lunch Workshop (ILW)
Session Description
Despite significant advances in diagnostic tools and disease characterization, neurologists across subspecialties continue to encounter patients with atypical or undiagnosed presentations. These complex cases—spanning neuroinflammatory to neurodegenerative conditions—often fall outside conventional diagnostic frameworks and present ongoing clinical challenges.
This session will explore potential mechanisms underlying these atypical neurological disorders, emphasizing emerging insights, diagnostic gaps, and the need for innovative approaches. Faculty will highlight the role of multidisciplinary collaboration and future research in improving recognition, classification, and management of these challenging conditions.
Learning Objectives
At the conclusion of this session, attendees will be able to:
- Analyze the clinical and societal burden of undiagnosed neurological diseases.
- Identify local and national resources to support referral and diagnostic evaluation of complex cases.
- Evaluate the role of multidisciplinary collaboration and national registries in advancing diagnosis and care.
Speakers
Bridging Clinical Complexity and Genetic Discovery
Description
Patients with rare, atypical, or unexplained neurological disorders often face prolonged diagnostic journeys that delay treatment, limit access to appropriate care, and create significant uncertainty for patients and their families. Advances in genomic medicine and multidisciplinary collaboration are transforming the evaluation of these complex cases, providing new opportunities to uncover underlying diagnoses and expand our understanding of neurological disease.
This presentation will explore the evolution of the NIH Undiagnosed Diseases Program and its role in providing diagnostic answers for individuals with complex and atypical neurological presentations. Participants will learn how comprehensive clinical phenotyping, advanced genomic technologies, and collaborative multidisciplinary approaches are integrated to identify rare neurological disorders and discover novel disease mechanisms. Topics will also include how insights gained through the program have advanced precision medicine, informed patient care, and contributed to the broader understanding of neurological disease.
Attendees will leave with a greater understanding of innovative approaches to diagnosing challenging neurological cases and the critical role that genomic discovery, interdisciplinary collaboration, and precision medicine play in improving outcomes for patients with rare and undiagnosed neurological disorders.
Atypical Manifestations of Neuroinfectious Diseases
Description
Neuroinfectious diseases can present with a wide spectrum of clinical manifestations, and in some cases, persistent viral adaptation within the central nervous system can lead to chronic neurodegeneration. These atypical presentations, often occurring in the setting of immune dysregulation, present significant diagnostic and therapeutic challenges for clinicians.
This presentation will examine cases of chronic neurodegeneration resulting from viral adaptation in the brain, highlighting the complex relationship between infectious agents, host immune responses, and progressive neurological disease. Participants will review illustrative clinical cases, explore the mechanisms by which viral persistence and immune dysregulation contribute to neurodegeneration, and discuss the diagnostic approaches and clinical considerations involved in recognizing these uncommon neuroinfectious disorders. Topics will also include the implications of these findings for patient management and future research.
Attendees will leave with a deeper understanding of the atypical manifestations of neuroinfectious diseases, increased awareness of the role of viral adaptation and immune dysregulation in chronic neurological illness, and practical insights for evaluating complex neuroinfectious presentations in clinical practice.
