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Long-term outcomes after new onset seizure in children living with HIV: A cohort study
Gretchen L Birbeck1,2,3, Musaku Mwenechanya2, Ifunanya Ume-Ezeoke1
1Department of Neurology, University of Rochester, Rochester, New York, USA.
Insights
Mortality remains high for children living with HIV (CLWH) after new onset seizures. Recurrent seizures are common, particularly in high-functioning CLWH without central nervous system opportunistic infections.
Area of Science:
- Pediatric Neurology
- Infectious Diseases
- HIV/AIDS Research
Background:
- Children living with HIV (CLWH) presenting with new onset seizures face significant long-term risks.
- Understanding these outcomes is crucial for managing this vulnerable population.
Purpose of the Study:
- To determine long-term mortality and seizure recurrence in children living with HIV (CLWH) following a new onset seizure.
- To identify risk factors associated with these outcomes.
Main Methods:
- Prospective enrollment of Zambian CLWH with new onset seizures.
- Follow-up to identify recurrent seizures and death, with statistical adjustment for mortality.
- Evaluation of demographic, clinical, and etiological factors.
Main Results:
- High mortality rate: 38% (28/73) died, with 22 deaths within 30 days.
- Seizure recurrence observed in 19% of the entire cohort; 27% among survivors at 30 days.
- Central nervous system opportunistic infections (CNS OI) were protective against recurrence, while higher functional status was a risk factor.
Conclusions:
- Elevated mortality risk persists beyond the acute phase for CLWH with new onset seizures.
- Recurrent seizures are frequent, especially in higher-functioning children without CNS OI.
- Need for antiseizure medications compatible with antiretroviral therapy and targeted interventions for CNS OI.
Objective:
To determine the long-term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure.
Methods:
Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30-day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality.
Results:
Among 73 children enrolled, 28 died (38%), 22 within 30-days of the index seizure. Median follow-up was 533 days (IQR 18-957) with 5% (4/73) lost to follow-up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30-days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86-269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence.
Significance:
Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co-usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures.
Plain Language Summary:
This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.
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