New-onset refractory status epilepticus (NORSE)--The potential role for immunotherapy

Ayaz M Khawaja; Jennifer L DeWolfe; David W Miller; Jerzy P Szaflarski

doi:10.1016/j.yebeh.2015.04.054

New-onset refractory status epilepticus (NORSE)--The potential role for immunotherapy

Epilepsy Behav. 2015 Jun:47:17-23. doi: 10.1016/j.yebeh.2015.04.054. Epub 2015 May 23.

Authors

Ayaz M Khawaja¹, Jennifer L DeWolfe², David W Miller³, Jerzy P Szaflarski⁴

Affiliations

¹ Department of Neurology, University of Alabama at Birmingham Hospital, Birmingham, AL, USA. Electronic address: dr.ayazmk@gmail.com.
² Department of Neurology, University of Alabama at Birmingham Hospital, Birmingham, AL, USA.
³ Department of Anesthesiology, University of Alabama at Birmingham Hospital, Birmingham, AL, USA.
⁴ Department of Neurology, University of Alabama at Birmingham Hospital, Birmingham, AL, USA; University of Cincinnati Department of Neurology, Cincinnati, OH, USA.

PMID: 26010959
DOI: 10.1016/j.yebeh.2015.04.054

Abstract

New-onset refractory status epilepticus (NORSE) is defined as a state of persistent seizures with no identifiable etiology in patients without preexisting epilepsy that lasts longer than 24h despite optimal therapy. Management of NORSE is challenging, and the role of immunotherapy (IT) is unclear. We identified patients fulfilling the criteria for NORSE at a single institution. These patients were described, analyzed, and compared with NORSE cases available from the literature. Finally, a pooled analysis of available case series was conducted to compare the outcomes in patients who received IT with those not treated with IT during the course of NORSE in order to generate hypotheses for further research. In our case series, NORSE was diagnosed in 11 patients (9 females) with a mean age of 48 years and a mean duration of 54.4 days. Autoantibodies were identified in 7 patients, of which anti-GAD (glutamic acid decarboxylase) and anti-NMDAR (N-methyl-D-aspartate receptor) were most frequent. Of the 11 patients, 8 were treated with IT (intravenous steroids, immunoglobulins, plasmapheresis, or a combination), and 4 received chemotherapy. Of the 8 patients treated with IT, 6 had favorable outcomes (defined as any outcome other than death, vegetative state, or inability to take care of oneself) compared with 0 out of 3 patients who did not receive IT. Difference in outcomes was significant (p=0.026). Pooled analysis of all identified case series, including ours, showed a statistically significant effect (p=0.022), with favorable outcomes in 42% of the patients who received any IT compared with 20% in those who did not. In all patients with refractory SE and negative comprehensive investigations, a diagnosis of NORSE should be considered. This would aid planning for early immunotherapy. Currently, only Class IV evidence for the use of immunotherapy in NORSE is available. Prospective multicenter studies are necessary to assess the true efficacy of IT in NORSE.

Keywords: Chemotherapy; Immunotherapy; NORSE; Outcome; Status epilepticus.

MeSH terms

Adult
Anticonvulsants / therapeutic use
Autoantibodies
Case-Control Studies
Female
Glutamate Decarboxylase
Humans
Immunoglobulins, Intravenous / therapeutic use
Immunotherapy*
Male
Middle Aged
Prospective Studies
Receptors, N-Methyl-D-Aspartate / immunology
Seizures / complications
Status Epilepticus / diagnosis*
Status Epilepticus / drug therapy
Status Epilepticus / therapy*
Treatment Outcome

Substances

Anticonvulsants
Autoantibodies
Immunoglobulins, Intravenous
Receptors, N-Methyl-D-Aspartate
Glutamate Decarboxylase