Abstracts

Rationale: New-onset refractory status epilepticus (NORSE) is a disease with significant morbidity. Leptomeningeal enhancement on contrast-enhanced magnetic resonance imaging (MRI) reflects severity of inflammation and blood brain barrier (BBB) disruption. Since BBB dysfunction and epileptogenesis are known to be closely related, we hypothesized that leptomeningeal enhancement may predict poor prognosis in NORSE patients. Therefore, we investigated whether prognosis differs according to leptomeningeal enhancement in NORSE patients. Methods: We retrospectively reviewed status epilepticus (SE) patients admitted to our hospital between March, 2013 and May, 2017. Among them, NORSE patients were selected according to the newly proposed consensus definition for NORSE in 2018. In particular, patients with active epilepsy, currently taking anti-epileptic drugs, acute structural lesions, or toxic-metabolic causes were excluded. All the patients underwent electroencephalography, contrast-enhanced MRI, cerebrospinal fluid (CSF) analysis, viral polymerase chain reaction (PCR), and autoimmune antibody tests including anti-NMDA receptor antibodies. NORSE patients were categorized as having good (=4) or poor outcome (=3) according to Glasgow Outcome Scale. Results: A total of 152 SE patients were recruited. Among them, 29 patients (42.1±17.0, men 62%) were identified as NORSE. Twenty three patients (79%) were cryptogenic NORSE patients, while 2 patients showed positive autoimmune antibody (anti-NMDA receptor antibody or autoantibody related to Hashimoto’s encephalopathy), 3 patients were NORSE related to remote structural lesion and last one was resolved epilepsy patient. Among 27 patients who underwent contrast enhanced MRI, 6 patients (22%) showed leptomeningeal enhancement. The percentage of poor outcome in NORSE patients with leptomeningeal enhancement was significantly higher than that in the patients without leptomeningeal enhancement (83 % vs. 14%, odds ratio (OR) = 30.0, p-value = 0.004). The percentage of leptomeningeal enhancement was higher in patients with pleocytosis in CSF analysis compared to that in patients without pleocytosis (43% vs. 0%, p-value = 0.016). Similarly, the percentage of leptomeningeal enhancement was higher in patients with elevated CSF protein level than those with normal CSF protein level (43% vs. 0%, p-value = 0.016). In the subgroup of 23 cryptogenic NORSE patients, the rate of poor outcome was higher in patients with leptomeningeal enhancement (83% vs. 12%, OR = 37.5, p-value = 0.003). In this subgroup, the rate of poor outcome was higher in patients with multi-lobar involvement (55% vs. 45%, OR = 13.2, p-value = 0.027).  Conclusions: Leptomeningeal enhancement was significantly associated with poor prognosis in patients with NORSE. In addition, patients with leptomeningeal enhancement showed more severe inflammation, that is, pleocytosis and elevated protein level in CSF. Therefore, we can speculate that BBB disruption caused by severe inflammation might cause poor outcome in NORSE patients. Further studies are needed to define the causal relationships among these. Funding: None