Research Assistant / Student Yale University / Brown University Darien, Connecticut
Rationale: To establish a collection of clinical data and biological samples that enables researchers to investigate the cause(s), outcomes, and best treatments for patients with NORSE. Methods: A prospective, observational, multi-center cohort study of adult and pediatric (> 6y) patients with NORSE (including its subtype of FIRES (febrile infection related epilepsy syndrome), defined for this study as refractory status epilepticus (RSE) with no identifiable etiology within the first 24h and no prior history of epilepsy. Exclusions included major ongoing acute or subacute medical conditions (e.g., sepsis) at the time of NORSE onset. The aim is to enroll 100 patients. Results: Thirty patients from 25 centers have been enrolled to date. Twenty-four (80%) were female and 27 were > 18 y of age. Median age of patients was 44 years (range 7-85). Average length of hospital stay was 22.5 days (range 6-121). 41% also qualified as FIRES due to prior febrile illness starting 24h – 14 days prior to RSE. Twenty-eight patients had serum and CSF samples collected. CSF WBC were > 10 wbc's/uL in 12. Serum Mycoplasma pneumonia IgM and Chlamydia pneumonia IgM was tested in 14 patients, with positive results in 4 and 1, respectively. Relevant antibodies included NMDA-R in three patients (1 in CSF and serum, 2 in CSF only) and GAD in four patients (1 in CSF and serum, 3 in serum only). Immune therapy was given to 23/30 patients, beginning a median of 4.5 days (range 0-23) after RSE onset, including steroids (n=22 patients), IVIG (n=11), plasmapheresis (n=11), tocilizumab (n=1) and rituximab (n=3). Nine (30%) patients died during hospitalization; eight of these nine received immune therapy within a median of two days. Nine of 21 survivors reached the six-month follow up visit; 7 had moderate disability or better, and 2 had severe disability. At 12 months, three of four patients had very good outcome based on Glasgow Outcome Scale-Extended (GOS-E). Conclusions: The interim results of this prospective multi-center NORSE study are consistent with prior literature with the exception that patients are receiving immunotherapy more frequently and earlier in their course; there is a possible trend towards improved outcome but mortality remains high (30%). The study is ongoing and biological samples are being processed and stored for future analysis. Funding: Please list any funding that was received in support of this abstract.: Acknowledgment: This study is supported by the Daniel Raymond Wong Neurology Research Fund at Yale University and the NORSE Institute.
