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Can we extinguish the seizures in FIRES?

Dr Sukhvir Wright

Dr Sukhvir Wright

Endeavour Project Awardee

Date Published: May 23, 2024

Author: James Matejka

Febrile infection-related epilepsy syndrome, or “FIRES”, is a condition characterised by sudden onsets of relentless, difficult-to-treat seizures – sometimes hundreds a day. Dr Sukhvir Wright is developing a new method to study the underlying causes of FIRES and test treatments to counteract it. Sukhvir will also collect information on current FIRES treatments to help her develop new treatment guidelines. In this blog, Sukhvir discusses how she hopes her work could transform the lives of children and adults affected by FIRES. 

What is FIRES?

FIRES is a dramatic name for an epilepsy syndrome, but one that fits. In people with no previous history of epilepsy, a seemingly minor febrile illness (having or showing the symptoms of a fever) unexpectedly escalates rapidly into life-threatening, treatment-resistant status epilepticus. This takes place within 24 hours to two weeks. Patients experience hundreds of seizures a day in the acute phase of the condition and must often be placed in a medically induced coma to try and protect the brain. This explosive-onset blaze of seizures is then followed by chronic epilepsy, still treatment-resistant, and often associated with subsequent life-changing acquired brain injury. FIRES was first described in typically developing healthy children around 60 years ago, but we now know it can affect all ages.

FIRES is classified as a subtype of “NORSE” – new-onset refractory status epilepticus. Both syndromes share the features of sudden-onset high seizure frequency in people not known to previously have epilepsy, and resistance to standard anti-seizure medications (ASMs). Thankfully, FIRES is relatively rare, with an incidence of approximately 1 in a million in Europe. In the US, it is estimated that 3200 cases of NORSE are seen per year. However, 12% of children and 30% of adults affected with FIRES/NORSE will die. In paediatric survivors of FIRES, only one in four wil recover back to their pre-disease functioning levels. Although full recovery is possible, a return to ‘normal life’ after FIRES/NORSE is sadly rare.

What starts the FIRES and what extinguishes them

In most cases, particularly in children, we do not know why FIRES starts. The explosive seizures do not respond to treatment and there is also currently no specific treatment pathway that is universally effective. Recent studies have shown that the fluid surrounding the brain and spinal cord, cerebro-spinal fluid (CSF), when sampled from FIRES patients often reveals high levels of molecules associated with inflammation. Some of these molecules have been shown to cause seizures in laboratory models and could hold the clue to the cause and potential treatment of FIRES.

How is our team of “FIRE(S)-fighters” helping?

Our team is made up of doctors who treat patients with FIRES, doctors who specialise in immunology, and scientists investigating why the brain develops seizures (epileptogenesis). With our combined knowledge and expertise, we are currently working on:

  • developing an urgently needed laboratory model of FIRES using patient derived CSF to further our understanding of how FIRES develops
  • using this model to test new and established treatments in FIRES
  • identifying UK paediatric cases to collect clinical information about current treatments and outcomes, and use this to inform best-practice guidelines for FIRES management

Additionally, we are part of an international collaborative NORSE/FIRES network whose primary aim is to facilitate research into understanding these devastating epilepsies and discover the most effective treatments.

There is a lot we do not yet know about FIRES. But what we do know is that is has catastrophic consequences on patients and their caregivers that can persist long after they leave hospital. The team’s hopes for this and future epilepsy research projects are that by partnering with doctors, scientists, patients and families we will make much-needed advancement in our understanding and treatment of FIRES/NORSE. We whole-heartedly thank the supporters of Epilepsy Research UK for making this project possible and look forward to updating you in the future on the progress of this research.