Inflammation and Febrile Seizures - Is There a Link?

Febrile seizures (seizures associated with a fever) are common in small children and are harmless for the most part. But seizures that last longer than 30 minutes (known as febrile status epilepticus or FSE) can be associated with epilepsy later in life. But, not all individuals that experience FSE go on to develop epilepsy as adults. Why is that the case?

Rodents like rats and mice are routinely used in the lab to study epilepsy to eventually come up with better therapies. A recent study came up a technique where only a subset of rat pups developed epilepsy after experimental FSE to mimic what happens in people. Previous research has linked inflammation to fever and to epilepsy. The scientists now wanted to know whether there was a more direct relationship between fever and inflammation that could cause epilepsy.

Tools Used

• The scientists subjected rat pups to FSE. A few months later, a subset of them developed epilepsy and the others didn’t.
• The areas of the brain that the scientists looked at were the hippocampus and the amygdala because of their importance in epilepsy.
• Magnetic resonance imaging (MRI) similar to that used for people was used.
• Immunohistochemistry and Western Blotting were used to visualize and quantify inflammatory mediators.

Findings

• Glial cells (as opposed to neurons) are known to become activated in response to injury. In this study too, astrocytes and microglia (specific kinds of glial cells were activated.
• Cytokines (mediators of inflammation) were also increased in the rats after FSE. Interestingly, there was considerable variability between animals. Some rats showed substantial increase in cytokines, whereas others showed no change, and a few fell between these two extremes.
• There was a close correlation between MRI signal and inflammation - rats that were subject to FSE and developed epilepsy were the ones that showed the increase in cytokines and a change in MRI signal. The ones that didn’t go on to develop epilepsy showed neither of these changes.

Conclusions

Unlike humans, experimental rats are highly identical genetically, so the fact that even then we would see these differences in MRI and in inflammation is remarkable. More research is needed in this field, but this study suggests that inflammation is a possible mechanism behind epileptogenesis and could also be a potential biomarker.