Febrile infection-related epilepsy syndrome

FIRES start with a febrile illness up to two weeks before seizure onset.[8] The clinical characteristic of FIRES is the onset of fever before the onset of SE.[8] The fever gradually decreases and then subsides when the seizures occurred.[8] SE is obstinate to treatment and continued for a few weeks.[8] The chronic phase of uncontrollable epilepsy leads to various degree of cognitive impairments.[8] These seizures damage the frontal lobe's cognitive brain function such as memory and sensory abilities.[2] behavioral disorders, memory issues, sensory changes, and possibly death. Children continue to have seizures throughout their lives.[2] Prolonged status epilepticus triggered motor disability in the patients with FIRES.[9] The severity of symptoms vary person to person, there are few symptoms that can be seen in a person with FIRES.[4] The severity of symptoms vary person to person, there are few symptoms that can be seen in a person with FIRES.[4] Before any neurological symptoms, fever can be observed in many cases, afterward seizures developed.[10] Cognitive ability can be impaired by repeated and continuous seizures.[11] The damage mainly occurred in frontal and temporal lobe regions and resulted in learning disorder, memory function impairment, and motor function impairment.[11]

• Autoimmunity
• Behavioral abnormality
• Cough
• Developmental regression
• Focal-onset seizure
• Headache
• Lethargy
• Pain in muscle
• Sinus inflammation [4]
• EEG abnormality
• Fever
• Myalgia[7]

The cause of FIRES is not known.[5] The reasons behind Febrile Infection-Related Epilepsy Syndrome are unidentified.[7] There are some common clinical symptoms, such as onset after a nonspecific febrile illness, gastrointestinal illness, or upper respiratory infection.[5] This prior illness is often cleared 1–14 days prior to the patient's first seizures.[5] It can be assumed that it is associated with metabolic problems, infection, and autoimmune disorders.[7] There are theories of an immunological source, a genetic predisposition, and an inflammation-mediated process, but the definite cause is unknown.[6][12] It is more common in boys than girls.[6][12] Fever is supposedly a risk factor for Febrile Infection-Related Epilepsy Syndrome.[7] As FIRES is an autoimmune disorder, any infection can be activated it.[13] Neuroinflammation can also be observed as one of the underlying causes of FIRES.[10][14]

FIRES is difficult to diagnose due to its rarity and lack of definitive biomarkers.[11] The diagnosis of FIRES is mostly clinically based due to a lack of identified sources.[11][15] The clinical features consist of remediable and not remediable infections and metabolic causes which help to develop the super-refractory SE, which leads to febrile illness.[13] It is often diagnosed by ruling out other options such as infectious, toxic, metabolic, and genetic causes.[13] FIRES can be misinterpreted as infection encephalitis, this is one of the great reasons for misdiagnosed FIRES.[13] There is no availability of genetic testing or biological markers.[15] The patients presented with a history of febrile illness moistly upper respiratory tract infection, gastroenteritis, etc., and also numerous episodes of seizures (50-10/day), which developed shortly.[15] Hyperacute phase abnormalities can be seen in EEG findings for FIRES.[11]

FIRES can be diagnosed by the below-mentioned examinations:[7]

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies

FIRES is a rare disease estimated prevalence of 1-10 per 100,000.[9][7] The mortality and morbidity rate in Febrile infection-related epilepsy syndrome (FIRES) is significantly high.[9] Those who have survived due to the medication therapy have acquired drug-resistant epilepsy and also intellectual disability.[9] Febrile infection-related epilepsy syndrome (FIRES) affected both adults as well as children, but it is more common in children.[16] The consequence of FIRES is unfortunate, the death rate of up to 30%.[15] Among 60%-100% of the children who survived, later develop mild to severe cognitive impairment, learning disabilities.[16] The mortality rate is about 10%-11% in FIRES.[9] Most of the patients died due to sepsis, obstinate status epilepticus, and also hazardous of treatment.[9] The mortality rate in the severe phase is between 10-11%.[9] The major reasons behind the mortality, are uncontrollable SE, limitations, difficulties in treatment, and also sepsis.[9]

he clinicians often faced difficulty to treat FIRES using antiepileptic drugs.[17] There is evidence of a very subtle response against anticonvulsant by the patients of FIRES.[18] In some cases, to control the seizures, the patient frequently needs deep sedation with anesthetic drugs.[17] Long-term treatment plan is also necessary for FIRES.[13]

FIRES was named in 2008 by Dr. Andreas van Baalen and colleagues.[24] Previous names include AERRPS (acute encephalitis with refractory, repetitive partial seizures), DESC (Devastating Epilepsy in School-aged Children),[25] and NORSE (New-Onset Refractory Status Epilepticus).[25]

EEG findings suggest FIRES is a focal process with focal onset seizures. In a 2011 study of 77 FIRES patients, 58 had focal seizures. Of the 58, 50 had secondarily generalizing seizures (seizures that evolve from focal to generalized).[2][26] On a 10-20 scalp electrode EEG, the ictal activity commonly begins temporally and spreads hemispherically and/or bilaterally.[27] Interictally, patients may have slowing that may be considered an encephalopathic pattern.[28] A recent study of 12 FIRES patients demonstrated diffuse delta-theta background slowing interictally in all 12 cases.[29]