Project start date: 01-Apr-2023 Project end date: 31-Mar-2025
New Onset Refractory Status Epilepticus/ Febrile infection-related epilepsy syndrome (NORSE/FIRES)
Febrile infection-related epilepsy syndrome is a new-onset refractory status epilepticus (NORSE) following a febrile infection, with fever starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus.
Age range for cases: 2 years to 18 years old.
Great Ormond Street Hospital, London
Great Ormond Street Hospital
Great Ormond Street
WC1N 3JH London
Email: marios.kaliakatsos@gosh.nhs.uk
1. Patients without active epilepsy or other pre-existing relevant neurological disorder, AND
2.with new onset of refractory status epilepticus without a clear acute or active structural, toxic, or metabolic cause, OR
3.new-onset refractory status epilepticus (NORSE) following a febrile infection
4. fever starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus.
5. Male or Female Children and young adults aged between 2-18
Reference: Hirsch, L.J., et al., Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia, 2018. 59(4): p. 739-744.
1. clear acute or active structural, toxic or metabolic cause
2. children less than 2 years of age and over 18 years.
Dr Sukhvir Wright, Wellcome Trust Clinical Research Career Development Fellow and Honorary Consultant Neurologist, Aston University, Birmingham
Dr Suresh Pujar, Neurology Consultant, Great Ormond Street Hospital, London
Dr Dimitrios Champsas, Clinical Research Fellow, Institute of Neurology, UCL, London
Expected numbers
Expected numbers (per year): 10 new cases per year. We consider that this will be increased as retrospective data will be added.
Source of denominator data:
1. In Germany, the annual incidence and prevalence of FIRES among children and adolescents is estimated to be 1:1 000 000 and 1:100 000 respectively (Specchio N., Developmental Medicine & Child Neurology, 2020)
2. American Epilepsy Society, NORSE expert meeting, 4th of December 2021
Ethical approval
The majority of studies will require research ethics committee (REC) approval.
If this is an audit study that does not require formal ethical approval, please forward to the BPNSU a copy of the confirmation from your REC that ethical approval is not needed.
If this study does have ethical approval, then please forward a copy of the ethics application and a copy of the approval letter.
IRAS Project ID: 311065, application under submission
Notification of cases: All doctors in the UK subspecialised or with special interest in Paediatric Neurology will receive a monthly notification to declare all cases with FIRES that they have come across and previously treated. This monthly notification email will be sent through the BPNSU, the major surveillance, research, and disease registry portal for UK paediatric neurologists. If the doctor has seen a case they will reply positively to this email that they have a case.
Identification of case and consent: The key investigators will approach the notifying doctor and verify the case falls within our case definition. The notifying doctor will then take consent from the patient's family/carers to:
1. Complete a standardised case report form (Appendix I) which will collect anonymised data on demographics, preceding illness, disease course, requirement for intensive care, co-morbidities, laboratory, imaging (MRI) and neurophysiology (EEG) results, treatments and outcomes.
2. Allow anonymisation and secure transfer of MRI images and EEG recordings.
3. Allow the study team to contact the family for further information if required.
4. Allow samples of stored CSF to be used for future laboratory research.
5. Allow follow-up questionnaires to be completed by their notifying doctor at 1 and 5 years after their disease onset (applies to prospective patients and retrospective patients from 2021 only)
We will provide the notifying clinician with participant information sheets (for the parent/carer) and consent forms (Appendix II and III).
Data collection and storage: The notifying doctor will fill out the standardised case report form digitally and send by secure NHS email to our named researcher Dr Champsas. This form will be stored in a password protected folder and anonymised by Dr Champsas to contain only a study ID code. Data will be entered in a password-protected (.csv file) by Dr Champsas, access to this database will be restricted to key investigators (Dr Kaliakatsos, Dr Wright, Dr Pujar and Dr Champsas).
MRI and EEG data: Dr Champsas will download the MRI images and EEG files from PACS/ EEG database. Dr Champsas will anonymise them by deleting all sensitive data and save the new files as their study ID code in an encrypted, password-protected hard drive.
Control CSF samples: The research team will identify patients that have other neurological diseases and have CSF samples stored that could be used as control samples for experiments. These patients will be asked to donate their samples and basic clinical details will be collected. The research participant will not undergo any additional testing or questioning, all the data will be provided by the reporting clinician, with their consent. Any samples of CSF consented for will be those that are or have been taken during a lumbar puncture as part of routine clinical care. No additional procedures will be done for research samples only.