Targeting Neuropathogenesis of Altered Mental Status to Improve Survival in Cryptococcal Meningitis

Dr. Mahsa Abassi is an Assistant Professor of Medicine in the Division of Infectious Diseases at the
University of Minnesota. She has been engaged in clinical research, focusing on AIDS related neuroinfections
in Uganda. Her long-term objective is to become an independent clinical researcher with an emphasis on
improving outcomes in neuroinfections.
Dr. Abassi’s Career Development Plan will provide her with the mentorship support, didactic course
work, and hands-on training she will need to become an expert in clinical and translational research with a
focus on HIV-associated neuroinfections. Her career development plan proposes mentored training in: 1)
neurologic techniques (EEGs and neuroradiology), 2) laboratory techniques related to metabolomics
applications, 3) advanced training in clinical research and translational medicine, and 4) biostatistics with an
emphasis of analyzing metabolites in biologic samples.
Research: Cryptococcal meningitis accounts for 15% of HIV/AIDS-related deaths, globally. Altered
mental status at the time of cryptococcal meningitis diagnosis is consistently an independent predictor of
increased mortality. Despite repeated studies confirming this strong association between altered mental status
and death, there is a fundamental lack of understanding into the exact neurological abnormalities leading to
altered mental status, its contributions to increased mortality, and best practices for management. The
objective of this proposal is to identify the neurological abnormalities that contribute to altered mental status
and to understand how it contributes to increased cryptococcal mortality. The overarching hypothesis is that
cryptococcal meningitis with its increased intracranial pressure leads to cerebral hypoxia, abnormal electrical
activity, and biochemical changes in the central nervous system (CNS) that can be detected through brain
metabolite CSF analysis and enhanced clinical monitoring with cerebral oximetry, EEGs, and ECGs. This
proposal aims to 1) determine if HIV-infected persons with cryptococcal meningitis presenting with altered
mental status (Glasgow Coma Scale (GCS) <15) at diagnosis have measurable underlying neurological
abnormalities and impairments in cerebral energy metabolism (i.e. insufficient oxidative metabolism) as
compared to persons with normal mental status (GCS=15), and 2) determine if implementation of standardized
clinical interventions can reverse neurological abnormalities and improve cerebral energy metabolism within 3
days of diagnosis,, and reduce 30-day mortality in HIV-infected persons with cryptococcal meningitis and
altered mental status (GCS<15). Results of the above aims will shed light into previously unknown
pathophysiologic mechanisms that lead to altered mental status in cryptococcal meningitis. The training in
metabolomics applications and clinical research that Dr. Abassi will obtain will inform future proposals on
evidence-based interventions dedicated to improving survival in HIV-associated neuroinfections.

Grant Number: 3K23NS122601-05S1
NIH Institute/Center: NIH
Principal Investigator: Mahsa Abassi