HIV and Cryptococcal Meningitis-Related Seizures: What Are the Outcomes?

Although bacterial and viral meningitis tend to make headlines—especially when they strike down previously healthy young people in America and other developed nations—cryptococcal meningitis, which is rare in people whose immune systems are uncompromised, plows a much greater path of destruction through less developed countries. According to the World Health Organization, fungus-based cryptococcal meningitis causes 15% of all HIV-related deaths—181,000 annually—most of which occur in sub-Saharan Africa.

Studies show that seizures are common in patients with meningitis of any kind, and they’re associated with more complications and worse outcomes; however, until now there have not been any studies specifically assessing the effect of seizures on HIV-positive people with cryptococcal meningitis. A team of investigators, led by University of Minnesota Medical School third-year student Katelyn Pastick, sought to clarify any connection between seizures and poor outcomes in HIV-infected patients in Uganda and South Africa based on 3 separate studies conducted between 2010 and 2017. The study was published in Open Forum Infectious Diseases.

The 3 studies together provided data on 821 people with HIV who contracted cryptococcal meningitis. In total, 28% experienced seizures, which is in line with the seizure rate of HIV-infected cryptococcal meningitis patients in previous studies. In the latest study, 15.5% of the subjects had seizures either before or at the same time the meningitis presented (baseline), and in 12.7% the seizures came after meningitis presentation (an average of 9 days later). All participants received medication to fight the meningeal infection, and slightly more than half who experienced seizures received anti-seizure medication within 1 week. Mortality rates were assessed at 2 weeks and 10 weeks past meningitis diagnosis.

The analysis of the 3 studies revealed that subjects who experienced seizures at any point had higher fungal burdens in their cerebrospinal fluid; had lower Glasgow Coma Scale scores, which measures functional response to various forms of stimuli; and were more likely to have elevated baseline cerebrospinal fluid opening pressures, which indicates intracranial pressure. These subjects were at significantly higher risk of dying 10 weeks after their meningitis diagnosis than subjects who had never had a seizure, and their neurocognitive functioning was poorer at 3 months post-diagnosis.

The timing of the seizures mattered as well: Fully half of participants who suffered seizures at or before meningitis presentation had died at the 10-week mark, while 40% of those who did not experience baseline seizures had died by then. However, when considering the timing of seizures that did occur, the researchers found that incident seizures occurring past the initial 2-week window were a harbinger of increased mortality.

The investigators acknowledged certain limitations to their study, including the likelihood that the seizure rate was underreported.

“Observed seizures were limited mainly to motor seizures as opposed to non-motor seizures, and a greater proportion of participants may have experienced non-motor seizures that were not observed or detected since EEGs were not available,” they wrote in the discussion section of their report. “Second, seizure events were not always directly observed, and events that were not in fact seizures may have been classified as seizures, resulting in possible misclassification.”

The authors also noted that subjects in the later study cohorts appeared to have significantly higher risk factors for seizures than those in the earlier cohorts. They surmise that this bump reflected an increasing awareness of seizures over time, as well as more sophisticated detection methods and more diligent reporting.