Neuroinflammation and Neuroinfection: Genetic Underpinnings to Neuroinflammatory and Neuroinfectious Diseases*

Experience of an adult neurogenetics clinic performing clinical next generation sequencing on adults with leukoencephalopathy, the types of disorders diagnosed along with management, guidelines and therapies in clinic or under development, if known

Inborn Errors of Immunity (IEIs) refer to genetic defects in immune-related genes that control host defense and immune response regulation. Among these patients, neurological disorders often represent a significant cause of morbidity and mortality. However, our understanding of the clinical presentations and underlying mechanisms of IEIs affecting neurons or the central nervous system (CNS) immune compartment remains limited. This presentation aims to introduce a novel platform designed to enhance the investigation of IEIs' role in the nervous system, providing an overview of various neurological manifestations associated with IEI. Additionally, insights from in-depth immunological and genetic investigations will be shared, highlighting their crucial role in diagnosing and treating patients with atypical and refractory neuroinflammatory and neuroinfectious diseases.

Adult genetic leukoencephalopathies are rare neurological disorders that present unique diagnostic challenges due to their clinical and radiological overlap with more common white matter diseases, notably multiple sclerosis (MS). In this context, collaborative multidisciplinary networks become critical to shorten the diagnostic odyssey of patients and preventing misdiagnosis. The White Matter Rounds (WM Rounds) network includes physicians and scientists from more than 15 participating sites around the world who gather every month to discuss patients with atypical white matter disorders. The experience of the WM Rounds Network demonstrates the usefulness of collective case discussions to accelerate the diagnostic process and prevent misdiagnosis in patients with rare or atypical white matter diseases. allow Besides allowing neurologists to compare and share information on challenging cases from across the world, networks of this nature provide a basis for multicenter research studies, and serve as model for other rare diseases.

Neuro-invasive West Nile Virus infection is a major cause of neurologic infections in endemic areas. Typically, in immunocompetent patients, diagnosis relies on detection of West Nile-specific IgM antibodies in CSF. In cases where patients are unable to mount an antibody response due to immunosuppression, a combination of WNV-specific IgM and PCT testing may be appropriate. We conducted a comprehensive analysis of testing utilization at two tertiary hospitals in Boston, Massachusetts, examining the medical records of adult patients who underwent West Nile-specific IgM or PCR testing from the CSF between 2016 and 2023. Most patients tested for neuro-invasive West Nile Virus relied solely on PCR for diagnosis, regardless of immune status. Rates of positive testing were low. This departure from guidelines in the majority of cases could potentially result in missed diagnoses and increased healthcare expenditures.