Febrile infection-related epilepsy syndrome (FIRES) is a sub-type of the condition “new-onset refractory status epilepticus” (NORSE). NORSE is where a healthy individual who has not previously experienced seizures begins having seizures.
With NORSE, seizures increase in duration and frequency over the course of several days, eventually culminating in a condition called status epilepticus.
In status epilepticus, an individual experiences a prolonged seizure or a cluster of seizures between which they do not regain consciousness.
Individuals with the FIRES subtype of NORSE also experience a fever in the days or weeks before their first seizure.
According to the National Center for Advancing Translational Sciences (NCATS), FIRES is a subtype of a condition called NORSE.
NORSE is a condition in which a healthy individual who has not previously experienced seizures begins having seizures.
These seizures increase in duration and frequency over the course of several days, culminating in a condition called status epilepticus.
In status epilepticus, a person experiences either a prolonged seizure or a series of smaller seizures without regaining consciousness between seizures. Status epilepticus may last days, weeks, or even months.
Individuals with the FIRES subtype of NORSE develop a fever somewhere between 2 days and 2 weeks before their first seizure.
This fever may or may not be present at the onset of status epilepticus, but in either case, is not the result of an infection.
According to the NCATS, FIRES is a rare condition, affecting fewer than 5,000 people in the United States.
Medical professionals previously believed FIRES only affected children but have since discovered that the condition can affect people of any age. However, most cases occur in children between the ages of 4 and 9 years.
As the NCATS explains, FIRES is a subtype of cryptogenic NORSE. The term “cryptogenic” indicates that the seizures occur without a known cause.
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This is because individuals with FIRES often have high levels of inflammatory markers, such as proinflammatory cytokines and chemokines, in their blood and cerebrospinal fluid (CSF).
The very first symptom of FIRES is a fever accompanied by a mild illness, such as gastroenteritis, or an upper respiratory tract infection (URI).
Individuals then begin to have seizures somewhere between 2 and 14 days later.
These seizures increase in duration and frequency over the course of several days, resulting in status epilepticus that may last anywhere from a few days to several months.
A 2018 review notes that around 50% of individuals with FIRES still have a fever when seizures begin, while the remaining 50% no longer have a fever when the seizures begin.
According to the 2018 review, FIRES can cause different types of seizures, each with different symptoms. The two main types of seizure and their associated symptoms are outlined below.
Since scientists do not yet know the cause of FIRES, no specific test can confirm the diagnosis.
The first step when diagnosing FIRES is to rule out other potential causes of status epilepticus, such as:
- infections
- toxin exposure
- metabolic causes
- genetic causes
According to the Epilepsy Foundation, doctors may order one or more of the following tests to help determine the cause of seizures:
- Prolonged electroencephalogram (EEG): This measures electrical activity in the brain over a period of 1 to 2 hours. This test can confirm the frequency of seizures and may show specific brain wave patterns associated with FIRES.
- Lumbar puncture: Involves using a needle to extract CSF from the spinal canal. This test can help to exclude underlying autoimmune disorders, as well as infectious causes of status epilepticus, such as meningitis and encephalitis.
- Blood tests: These can help to rule out treatable metabolic disorders.
- Genetic tests: These can help to rule out certain gene mutations that may lead to prolonged or recurrent seizures.
- MRI brain scan: Initial MRI brain scans may appear normal. However, subsequent scans taken weeks or months later may show abnormal brain signaling and brain atrophy.
- Brain biopsy: In rare cases, doctors may recommend a brain biopsy to rule out infection or inflammation.
Doctors may diagnose FIRES if a person experiences fever before status epilepticus and has no identifiable cause of seizures.
There is no standard treatment for FIRES.
The Epilepsy Foundation lists some drugs that doctors may use to treat seizures during the acute phase of FIRES. These include:
- benzodiazepines, such as lorazepam, and midazolam
- barbiturates, such as phenobarbital, and pentobarbital
- anesthetics, such as ketamine and lidocaine
- magnesium
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This reduces the likelihood of recurrent seizures. Doctors can then use EEG to determine the depth of the coma and to ensure that the seizures have stopped.
A 2020 review notes that FIRES has a mortality rate of up to 30%.
Among those who survive FIRES, most develop some form of cognitive impairment. According to a
One-third of people develop mild to moderate cognitive disability, whereas one-third develop severe cognitive disability or enter a vegetative state.
The latter is where an individual appears awake but shows no signs of awareness.
Factors that appear to increase the risk of cognitive impairment following FIRES include:
- being younger
- experiencing more severe seizures
- receiving delayed treatment for seizures
According to a 2020 review, most people who survive FIRES also go on to experience refractory epilepsy or “drug-resistant epilepsy”, where the seizures are not treatable using anti-seizure medications.
Recommendations for ongoing care
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Some of these recommendations relate to the post-acute phase of these conditions, which is the phase after which the seizures have ended.
According to these recommendations, most individuals in the post-acute phase of NORSE or FIRES should:
- follow a high fat, low-carbohydrate (ketogenic) diet for 3 months if the diet was effective during the acute phase of the condition
- undergo screening for sleep disorders and mood and psychiatric disorders, if possible
- undertake an intensive program of motor and cognitive rehabilitation, if possible
- use social service interventions to help with returning to work, studies, or social activities
- undergo cancer screening once per year for up to 5 years (for adults only) to ensure the seizures are not due to a developing cancer.
FIRES is a rare condition that causes a sudden onset of seizures following an illness in someone who previously did not experience seizures.
Medications can treat acute flare-ups of FIRES, but a person will need ongoing care.