Refractory Inflammatory Seizures in Kids (RISK)

Overview

About this study

The purpose of this study is to define the spectrum of inflammatory responses to pathogen and alarmin challenge in healthy children and in children with new onset refractory status epilepticus (NORSE) or drug-resistant epilepsy (DRE), to identify the molecular mechanisms underlying aberrant inflammatory responses to pathogen and alarmin challenge in a cohort of children with validated inflammatory drug-resistant seizures, and to measure alarmin-induced neuroinflammatory and electrophysiological responses in patient-specific iPSC-derived neural organoids.

 

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria - RISK Primary Inclusion Criteria: NORSE (~50 patients):

  • New onset refractory status epilepticus with or without fever.
  • Failure to respond to 2 or more first-line anti-seizure drugs.
  • Age 0 to 18 years.
  • Etiology for status epilepticus unknown:
    • No history of pre-existing epilepsy;
    • No pre-existing major developmental impairment;
    • No evidence of prodromal dyskinesia, hallucinations, or psychiatric symptoms;
    • No evidence of structural, cerebrovascular, neoplastic, metabolic, traumatic, or toxic etiology.

Inclusion Criteria - RISK Primary Inclusion Criteria: DRE (~150 patients):

  • Epileptiform abnormality on EEG.
  • Seizure frequency at least weekly.
  • Failure to respond to 2 or more first-line anti-seizure drugs.
  • Age 0 to 18 years.
  • Clinical and electrophysiological profile not consistent with:
    • self-limited focal epilepsy syndrome;
    • unifocal epilepsy.
  • Normal 3T epilepsy protocol MRI (if available).
  • Normal epilepsy panel or no evidence of known epilepsy mutations by whole exome sequencing (if available).
  • No evidence of autoimmune, cerebrovascular, neoplastic, metabolic, traumatic, or toxic etiology.

Inclusion Criteria - RISK Retrospective Recruitment Inclusion Criteria (~100 patients):

  • Prior diagnosis consistent with NORSE or DRE.
  • No evidence of autoimmune, infectious, structural, cerebrovascular, neoplastic, metabolic, or toxic etiology.
  • Negative genetic epilepsy panel.
    • Note: No exclusions based on disease-modifying therapies, including immunomodulatory or immunosuppressive treatments (e.g., IV corticosteroids, plasma exchange, intravenous immunoglobulin, and anti-cytokine drugs such as anakinra or tocilizumab).

Exclusion Criteria:

  • Validated autoimmune disorder.
  • Smoker.
  • Pregnant.
  • Weight < 9 kg.

Eligibility last updated 1/21/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Charles Howe, Ph.D.

Closed-enrolling by invitation

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"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Center for Multiple Sclerosis and Autoimmune Neurology

DLCMSANResCoor@mayo.edu

More information

Publications

Publications are currently not available