From the Research
New-onset refractory status epilepticus (NORSE) is a severe condition that can be associated with various neoplasms, particularly autoimmune encephalitis triggered by paraneoplastic syndromes, and its management should prioritize early immunotherapy and aggressive antiepileptic therapy. The most common neoplasms associated with NORSE include small cell lung cancer, ovarian teratomas, testicular tumors, breast cancer, and thymomas 1. When managing a patient with NORSE, a thorough malignancy workup should be conducted, including whole-body CT or PET scans, tumor markers, and when indicated, testing for paraneoplastic antibodies such as anti-NMDA receptor, anti-Hu, anti-Ma2, and anti-GAD65.
Key Considerations
- NORSE constitutes the acute phase of an entity preceded by a prodromal phase and followed by a chronic phase marked by long-term neurological sequelae, cognitive impairment, epilepsy, and functional disability 1.
- Paraneoplastic and non-paraneoplastic autoimmune encephalitis remains by far the leading cause of NORSE, emphasizing the importance of considering immunomodulatory interventions in refractory epilepsy cases 1.
- Immunotherapy should be initiated early, including IV methylprednisolone (1000 mg daily for 3-5 days), followed by IVIG (2 g/kg over 2-5 days) or plasmapheresis, and second-line immunotherapies like rituximab (375 mg/m² weekly for 4 weeks) or cyclophosphchrome-8 may be necessary in refractory cases 2.
- For tumor-associated NORSE, surgical resection of the neoplasm is crucial and often leads to significant improvement in seizure control.
Recent Evidence
- A recent study published in 2024 found that the long-term outcome can still be favorable in NORSE survivors, despite a prolonged and complicated ICU stay, emphasizing the importance of continuing treatment even in initially refractory cases 3.
- Another study published in 2025 suggested that tocilizumab, an interleukin-6 receptor antagonist, may represent a promising therapeutic strategy for NORSE, even if administered late in the course of this pathological condition 4.
Management Approach
- Aggressive antiepileptic therapy is required, often using combinations of medications like levetiracetam (1000-3000 mg/day), valproate (15-30 mg/kg/day), and lacosamide (200-400 mg/day).
- Early initiation of immunotherapy, including IV methylprednisolone and IVIG or plasmapheresis, is crucial in managing NORSE.
- A thorough malignancy workup should be conducted to identify potential underlying neoplasms associated with NORSE.