A retrospective cohort study of new‐onset refractory status epilepticus (NORSE): clinical features, timing of immunotherapy and outcomes

Abstract

Objective. To describe clinical characteristics associated with immunotherapy in patients with new-onset refractory status epilepticus (NORSE) and assess its timing and effect on outcomes at hospital discharge after six and 12 months of follow-up. Our secondary aim was to apply the cryptogenic NORSE (C-NORSE) score to subjects in order to evaluate its utility in identifying C-NORSE in our cohort. Methods. This was a retrospective single university hospital cohort study (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020)(2021) of adults and children with NORSE. First-line immunotherapy was defined as corticosteroids, intravenous immunoglobulin (IVIg), and plasmapheresis (PLEX). Early immunotherapy was defined as administration of a first-line agent within seven days of presentation.Results. Twenty-one subjects with NORSE were identified between 2004 and 2021, which was cryptogenic in 18 and immune-mediated in three. All patients received immunotherapy. Seventeen patients received early immunotherapy (81%). There was no significant difference between early versus late immunotherapy regarding "good or favorable" outcomes (mRS 0-2) at hospital discharge or during follow-up. For cryptogenic NORSE patients, 7/11 (64%) achieved good outcomes at six months, 9/11 (82%) at 12 months, and 8/10 (80%) at the last follow-up visit at >13 months. For immune-mediated NORSE patients, 3/3 (100%) achieved good outcomes at six months and 2/2 (100%) at the last follow-up visit at >13 months. In our cohort, a C-NORSE score of 5 was obtained in 12/18 (67%) of cryptogenic cases and a score <5 in all three immunemediated cases. Significance. There is a paucity of published data on the timing of immunotherapy for NORSE. Although at our institution early administration of immunotherapy is feasible, more research is needed to determine which patients may benefit from immunotherapy and if the timing of immunotherapy affects short and long-term outcomes. Among the patients who survived hospitalization, long-term follow-up of our NORSE cohort demonstrated that a subset achieved good mRS (0-2) scores.

Outcome of emergency neurosurgery in patients with refractory and super-refractory status epilepticus: a systematic review and individual participant data meta-analysis

“…Thus, patients with unexplained new onset seizures such as new onset refractory status epilepticus (NORSE) with generalized ictal EEG findings and diffuse or normal imaging findings could still benefit from these approaches. However, our logistic regression models revealed that new-onset seizures were associated with worse outcomes; thus, clinical decision-making should still be made on a case-by-case basis given the lack of high-quality evidence guiding therapy in these patients, as well as the documented role of therapies such as the ketogenic diet and immunotherapy ( 31 , 32 ). Some authors suggest the use of non-invasive neuromodulation techniques such as and transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) in the first week of SRSE, and consideration of neuromodulation techniques such as VNS, DBS and RNS after 2 weeks of therapy ( 33 ).…”

“…ketogenic diet and immunotherapy(31,32). Some authors suggest the use of non-invasive neuromodulation techniques such as and transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) in the first week of SRSE, and consideration of neuromodulation techniques such as VNS, DBS and RNS after 2 weeks of therapy (33).Although corpus callosotomy and MST remain viable options, their overall efficacy was equal or slightly inferior to neuromodulation…”

Specific profiles of new-onset vs. non-inaugural status epilepticus: From diagnosis to 1-year outcome

“…Are there certain etiologies that are particularly represented in refractory SE? In other series that focused specifically on the NORSE subgroup, the most common etiology was autoimmune encephalitis, while 52% of the cases of NORSE remained cryptogenic ( 3 , 28 , 31 , 77 ). No autoimmune encephalitis was identified in our NOSE cohort although this etiology was repeatedly suspected and sought, while two cases of autoimmune encephalitis were included in our NISE group with a refractory SE.…”

“…None of the studies cited above investigated the discriminating features between NOSE and NISE. In addition, little information is available on the paraclinical aspects associated with NOSE, and the most recent publications frequently focused on the refractory subtype of these de novo SE ( 2 , 3 , 31 ).…”

Risk factors for super-refractory and mortality in generalized convulsive status epilepticus: a 10-year retrospective cohort study

“…A previous small cohort study of 18 NORSE patients found that immunotherapy including PE did not change the prognosis of NORSE patients. 34 A RCT 35 of NORSE with immunotherapy (corticosteroids, IVIG, and PE) showed that it improves the prognosis (mRS 0–2) at hospital discharge and during follow-up despite early or late application. In this study, autoimmune encephalitis was the main etiology and PE was the first-line therapy for such patients, which may cause a different result.…”