DESC syndrome

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DESC syndrome in short

A rare and potentially life-threatening epileptic encephalopathy, FIRES (Febrile Infection-Related Epilepsy Syndrome) is marked by the sudden onset of recurrent multifocal and bilateral tonic-clonic seizures, typically following a non-specific febrile illness.
It occurs in individuals with no prior history of epilepsy and without an identifiable acute structural, toxic, or metabolic cause.
FIRES is considered a subset of new-onset refractory status epilepticus (NORSE), distinguished by the essential presence of a preceding febrile infection.

Age of onset: All ages

Based on a small cohort study from Germany, the estimated prevalence is 1 in 100,000, with an annual incidence of 1 in 1,000,000 among children and adolescents.
Global epidemiological data remains limited. In pediatric cases, there appears to be a male predominance, whereas females are more commonly affected in adulthood.
No familial cases have been reported to date.

Febrile Infection-Related Epilepsy Syndrome (FIRES) most commonly affects school-aged children. It typically begins in a previously healthy individual with the abrupt onset of recurrent multifocal and bilateral tonic-clonic seizures following a non-specific febrile illness.
This rapidly progresses to refractory—and often super-refractory—status epilepticus. The acute phase may persist for weeks to months.
This is followed immediately by a chronic phase, marked by treatment-resistant focal epilepsy and frequently accompanied by significant impairments in memory, cognition, and behavior. Motor disabilities are less frequently observed.

The exact cause of DESC syndrome remains unclear. It is most likely an immune-inflammatory-mediated epileptic encephalopathy, driven by a vicious cycle of inflammation and neuronal hyperexcitability.
Cerebrospinal fluid (CSF) findings and the typically limited response to immunotherapy suggest that innate immune system activation and autoinflammatory mechanisms, rather than autoimmune processes, play a central role. Variants in known epilepsy-related genes do not appear to increase susceptibility to FIRES.

A thorough diagnostic work-up is essential to rule out treatable conditions. In the early stages, magnetic resonance imaging (MRI) is often normal or may reveal signal abnormalities in the temporal lobes. As the condition progresses into the chronic phase, diffuse brain atrophy and changes in the mesial temporal regions are commonly observed.
Cerebrospinal fluid (CSF) analysis typically shows normal results or mild pleocytosis, with no evidence of pathogens, oligoclonal bands, or neuronal antibodies.
Metabolic evaluations are generally unremarkable, and genetic testing is performed to exclude hereditary epilepsies, such as those associated with POLG mutations. Continuous electroencephalogram (cEEG) monitoring is necessary to track seizure activity and assess the depth of anesthesia. In some patients, early EEG recordings may reveal beta-delta complexes resembling extreme delta brush.

The differential diagnosis is broad and includes conditions such as infectious or autoimmune encephalitis (e.g., anti-NMDAR encephalitis and other encephalitides associated with antineuronal antibodies, as well as acute disseminated encephalomyelitis), primary central nervous system angiitis, acute necrotizing encephalopathy, and other infection-related encephalopathies.
Metabolic disorders—such as mitochondrial diseases, citrullinemia, and disorders of thiamine metabolism—should also be considered, along with genetic epilepsies like Dravet syndrome and PCDH19-related epilepsy.

Intensive care monitoring is essential during the acute phase.
Seizures are typically resistant to standard anti-seizure medications, with high-dose benzodiazepines offering only temporary relief. In most cases, general anesthesia with barbiturates—titrated to achieve burst suppression—is required to control seizures, although prolonged burst suppression may be associated with poorer cognitive outcomes.
Seizures often recur upon awakening, leading to the need for repeated anesthesia. Immunotherapies generally show limited effectiveness; however, anakinra or tocilizumab has demonstrated significant benefit in a small number of cases.
Among treatment options, the ketogenic diet appears to be the most effective, particularly when started early, though no controlled studies are currently available.
Other interventions such as ketamine, inhalation anesthetics, cannabidiol, therapeutic hypothermia, and neurostimulation have shown short-term benefits in select cases.

DESC syndrome carries a poor prognosis, with a high likelihood of developing chronic, drug-resistant epilepsy and substantial cognitive impairment.
However, complete recovery has been documented in a small number of cases. In children, the mortality rate is approximately 12%.