Status Epilepsy Syndromes Made Easy: Pediatric Perspectives

Area of Science:

• Neurology
• Pediatric Neurology
• Epileptology

Background:

• Refractory Status Epilepsy Syndrome encompasses conditions like New-onset refractory status epilepticus (NORSE) and Febrile infection-related epilepsy syndrome (FIRES).
• Existing nomenclature for these syndromes is often conflicting and confusing.
• NORSE affects previously healthy children, while FIRES is considered a variant with a preceding febrile event; both often imply autoimmune or inflammatory origins.

Purpose of the Study:

• To provide an updated review of hypotheses, etiology, pathophysiology, clinical features, diagnosis, treatment, and future perspectives for NORSE/FIRES.
• To clarify the understanding and management of these complex neurological conditions.

Main Methods:

• A comprehensive literature search was conducted using PubMed Clinical Queries with keywords NORSE and FIRES.
• The search focused on human subjects up to May 2025, including reviews, systematic reviews, case series, and case reports.

Main Results:

• Seizures in NORSE/FIRES are typically recalcitrant, requiring treatments such as anti-seizure medications (ASM), ketogenic diet, and immunotherapy.
• Prognosis is often poor, with survivors frequently experiencing refractory epilepsy and cognitive impairment.
• New guidelines and consensus have improved clinical management, with specific diagnoses made once etiology (autoimmune, paraneoplastic) is identified.

Conclusions:

• NORSE and FIRES share similarities, though vagus nerve stimulation may be more effective in NORSE.
• A new unifying term, NOSES (New Onset Status Epilepticus Syndrome), is proposed for conditions characterized by new-onset status epilepticus lasting over 24 hours despite two standard ASMs.
• Autoimmune encephalitis, paraneoplastic conditions, and infectious encephalitis represent specific diagnoses within NOSES when the etiology is identified.