For neuropathology what is pretty difficult is that biospecimens can be collected at very large timepoints after status epilepticus onset. So, you have some biopsies that are mostly conducted during the acute phase of the disease. That means when the patient is still under continuous anti-seizure medication, so when the status is ongoing. But you also have some patients who died after NORSE; so currently we estimate that 30% of patients passed away during ICU hospitalization and for some of them, we have autopsy tissues that have been analyzed...
For neuropathology what is pretty difficult is that biospecimens can be collected at very large timepoints after status epilepticus onset. So, you have some biopsies that are mostly conducted during the acute phase of the disease. That means when the patient is still under continuous anti-seizure medication, so when the status is ongoing. But you also have some patients who died after NORSE; so currently we estimate that 30% of patients passed away during ICU hospitalization and for some of them, we have autopsy tissues that have been analyzed. And so, our idea with this neuropathology literature review was to investigate the most important dysregulation for these patients and also if this modulation can be applied to prompt us to design other immunotherapies. The most important things we observed is we described most of patients present with neuronal loss and astrogliosis with microglial reactivity. These three dysregulations are frequently observed in case of very frequent seizures. And so, it could be just a consequence of the status epilepticus.
But the result we found interesting is that some patients also had a cluster of immune T-cells in the brain. These cells should not be represented, should not be discovered in those patients. So that means that maybe the inflammation was also entered into the brain. And so you can have this type of populations in case of very refractory and very severe cases. It was interesting for us because the cytokine analysis let us know that it was mainly the innate immunity-related, pro-inflammatory cytokine that could trigger the pathogenesis. But based on the neuropathology findings, it seems that in some cases you also have an involvement of the lymphocyte T-cells.
So currently we may imagine that perhaps all of the patients have an activation of the innate immunity during the acute phase of the disease. But when the status persists for several weeks, for several months for some patients, you may also have an activation of the T-cell immunity, leading to an infiltration of the brain by lymphocyte T-cells. And in that case, it’s pretty hard to give a recommendation today because we just have few patients. But if such results are confirmed, we may suggest using anti T-cell therapy for patients who are refractory to all other immune therapies and who have a status epilepticus that persists.