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

• Published in: Epilepsy & behavior Vol. 47; pp. 17 - 23
• Main Authors: Khawaja, Ayaz M, DeWolfe, Jennifer L, Miller, David W, Szaflarski, Jerzy P
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2015
• Subjects: Adult; Anticonvulsants - therapeutic use; Autoantibodies; Case-Control Studies; Chemotherapy; Female; Glutamate Decarboxylase; Humans; Immunoglobulins, Intravenous - therapeutic use; Immunotherapy; Male; Middle Aged; Neurology; NORSE; Outcome; Prospective Studies; Receptors, N-Methyl-D-Aspartate - immunology; Seizures - complications; Status epilepticus; Status Epilepticus - diagnosis; Status Epilepticus - drug therapy; Status Epilepticus - therapy; Treatment Outcome; LZP; IVIg; PLEX; fosphenytoin; VZV; cytomegalovirus; Immunotherapy; fPHT; plasma exchange; angiotensin-converting enzyme; intravenous solumedrol; collapsin response mediator protein; new-onset refractory status epilepticus; HSV; GAD; IT; lorazepam; valproic acid; CMV; glutamic acid decarboxylase; PCA; voltage-gated calcium channel; Chemotherapy; NORSE; LCM; human immunodeficiency virus; NMDAR; antineuronal nuclear antibody; JCV; PCR; ANNA; VDRL; voltage-gated potassium channel; VPA; AGNA; thyroid peroxidase; antiglial nuclear antibody; cEEG; Purkinje cell antibody; CRMP; AEDs; herpes simplex virus; TPO; SE; lacosamide; EBV; FLAIR; fluid-attenuated inversion recovery; intravenous immunoglobulin; Epstein–Barr virus; WNV; polymerase chain reaction; VGKC; antiepileptic drugs; ACE; continuous electroencephalography; IVSM; Venereal Disease Research Laboratory; N-methyl- d-aspartate receptor; status epilepticus; HIV; JC virus; West Nile virus; Outcome; varicella zoster virus; VGCC; LEV; levetiracetam; Status epilepticus
• ISSN: 1525-5050; 1525-5069
• 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 24 h 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.