The high rate of postencephalitic epilepsy (PE) contributes to the unfavorable clinical outcome of herpes simplex virus-1 encephalitis (HSE). Researchers from Qilu Hospital of Shandong University conducted a study aimed at identifying risk factors and exploring potential mechanisms for PE following HSE, particularly among children.
The study involved retrospective reviews of 97 pediatric patients diagnosed with HSE, where the presence of PE was diagnosed in 46 of those subjects. The researchers employed multivariate logistic regression analysis to determine which clinical features were predictive of developing PE. Their findings revealed significant predictors—namely, status epilepticus, focal seizures, and restricted diffusion observed on MRI scans.
According to the team, the results showed increased levels of pro-inflammatory cytokines such as interleukin (IL)-6, coupled with greater blood-brain barrier (BBB) dysfunction as indicated by elevated QAlb values (cerebrospinal fluid to serum albumin ratio), which were measured during the acute phase of the infection.
"Enhanced BBB impairment and exaggerated pro-inflammatory response may play a role in the pathogenesis of PE following HSE," the authors noted, highlighting how neuroinflammatory responses can contribute to the development of epilepsy. They emphasized the necessity of identifying risk factors for PE, especially considering the increasing cases of HSE and its severe neurological impacts. The results of the cohort indicate the pressing need for careful monitoring of patients, as 67.4% of those who developed PE did so within the first year following their experience with HSE.
The findings are particularly relevant since HSE is the most common cause of sporadic fatal encephalitis worldwide, often resulting in significant morbidity and persistent neurological deficits, including epilepsy. Pro-inflammation following the acute phase of HSE seems to mediate the transition to chronic neurological conditions.
The study also examined CSF levels of various cytokines and found marked differences between those who developed PE and those who didn't. For example, CSF IL-6 levels were significantly elevated among children with PE, indicating the inflammatory response remains heightened post-infection. Conversely, levels of IL-10, known to regulate the inflammatory response, were decreased. This imbalance may suggest why some children experience persistent seizure activity following their initial infection.
The presence of restricted diffusion on MRI was also strongly correlated with the likelihood of developing epilepsy later on. The analysis determined this specific MRI finding might reflect severe underlying cerebral damage or neuroinflammation, factors likely to contribute to epileptogenesis.
To determine their findings' ramifications, the authors recommend rigorous follow-up protocols for children recovering from HSE, particularly during the first two years, when the risk for developing epilepsy is markedly pronounced. They advocate for these patients to be monitored closely and potentially referred to specialized epilepsy clinics to assess for any signs of recurrent seizures and facilitate timely interventions.
"Our study reinforces the involvement of dysregulated neuroinflammation in the pathogenesis of PE and may direct us toward new therapeutic interventions," the authors assert. They believe incorporating anti-inflammatory treatments could serve as a promising approach to mitigate the future risk of epilepsy developing after HSE.
Given the high rates of long-term neurological conditions following HSE and the growing body of evidence surrounding neuroinflammatory processes, this study contributes significantly to the developing discourse on pediatric neurological health. A multidisciplinary approach involving neurologists, immunologists, and pediatricians may be required for optimizing care for children affected by HSE.