An extreme type of new onset refractory status epilepticus with stimulus-induced seizures in pharmacological isoelectric states.

Objective: Status epilepticus (SE) is a common neurological emergency associated with high morbidity and mortality. SE is classified as refractory when it persists despite benzodiazepine and second-line antiseizure medication. Managing refractory SE in the intensive care setting often requires high doses of sedative drugs, which can induce burst suppression or complete electrical suppression (amplitude < 10 μV). We aimed to investigate the characteristics of persistent epileptic seizures in patients undergoing pharmacologically induced electrical suppression for treatment of refractory SE.

Methods: We retrospectively screened our hospital electroencephalographic (EEG) database for patients admitted to the neurointensive care unit with SE and a new onset refractory status epilepticus (NORSE) diagnosis from 2006 to 2024 (N = 65). Patients with persistent seizures despite a suppressed EEG were included. EEG, biological, and clinical data and outcomes were collected.

Results: We identified seven patients with persistent electrical seizures despite pharmacologically induced electrical suppression lasting >1 min. All had cryptogenic NORSE (c-NORSE), preceded by a febrile event, and showed cerebrospinal fluid inflammation. Electrical suppression was achieved using three to four sedative drugs, including a barbiturate. A specific seizure onset EEG pattern was identified in all, characterized by periodic and/or rhythmic generalized discharges (GDs), followed by faster, lower amplitude rhythmic activity. In two patients, increased sedation revealed a second seizure onset pattern, characterized by abrupt rhythmic activity over isoelectric EEG background, independent of GDs. In six patients, multimodal stimuli (auditory, visual, or tactile) triggered either seizures, interictal high-amplitude GDs, or both. Repeated stimuli were associated with small-amplitude evoked potentials. All patients died in the intensive care unit.

Significance: We report a series of seven c-NORSE patients with a rare and extremely severe presentation: persistent and stimulus-induced seizures occurring over an electrically suppressed EEG background. This hyperexcitability state may result from cellular and network alterations induced by phenobarbital in patients with central nervous system inflammation.