Second-line immunotherapy in new onset refractory status epilepticus

Area of Science:

• Neuroimmunology
• Epileptology
• Clinical Pharmacology

Background:

• Immune dysregulation is implicated in the pathogenesis of new onset refractory status epilepticus (NORSE) and its subtype, febrile infection-related epilepsy syndrome (FIRES).
• Established guidelines recommend first- and second-line immunotherapies for NORSE/FIRES patients.

Purpose of the Study:

• To review the current literature on the efficacy and outcomes of second-line immunotherapies for NORSE/FIRES.
• To analyze the use of anakinra, tocilizumab, and intrathecal dexamethasone in a cohort of NORSE patients.

Main Methods:

• Systematic review of 28 case reports and series.
• Analysis of data from 75 patients treated with anakinra, tocilizumab, or intrathecal dexamethasone.
• Examination of treatment initiation timing, seizure control, cytokine levels, and long-term outcomes.

Main Results:

• Anakinra (73%), tocilizumab (70%), and intrathecal dexamethasone (50%) achieved seizure control within two weeks in a significant proportion of patients.
• Cytokine levels generally decreased post-treatment; anakinra and intrathecal dexamethasone were more common in pediatric FIRES, while tocilizumab was used more in adults.
• Most patients experienced long-term disability and drug-resistant epilepsy; late initiation of immunotherapy showed potential seizure reduction in some cases.

Conclusions:

• Anakinra, tocilizumab, and intrathecal dexamethasone demonstrate potential utility as second-line treatments for NORSE/FIRES.
• Early cytokine level monitoring may aid in treatment selection and response assessment.
• Further prospective studies are essential to elucidate the role of early immunomodulation in epilepsy and functional outcomes.