Prognostic significance of subsequent extra-temporal involvement in cryptogenic new onset refractory status epilepticus (NORSE) initially diagnosed with limbic encephalitis

New-onset refractory status epilepticus (NORSE) is defined as refractory SE in patients without active epilepsy or relevant neurological disorder with no clear active causes. Diverse types and etiologies of NORSE are reported in various groups. Limbic encephalitis (LE) is reported as one of etiologies of NORSE. In this study, we investigated whether there were any intersections between NORSE and limbic encephalitis, as well as the presence of prognostic factors in intersection patients.

We retrospectively analyzed patients who met both the definition of NORSE and diagnostic criteria of LE at the initial presentation from our database. Clinical characteristics and blood test, cerebrospinal fluid, electroencephalography, and magnetic resonance imaging results were reviewed. Prognosis was recorded as ICU admission stay, total length of hospitalization, and modified Rankin Scale at discharge. In particular, we determined which factors were associated with patients' prognosis.

Thirteen patients were selected. Nine of the 13 patients had myalgia and 8 patients had fever in the prodromal period. Twelve of the 13 patients had acute memory impairment or confusion before SE development. In addition, 46.2% of the patients showed leukopenia or thrombocytopenia. Median body temperature at hospital arrival was 37.6 °C. Nine patients showed generalized tonic-clonic SE. All patients were treated with immunotherapy and 11 of the 13 patients achieved burst suppression through induced coma therapy. Ten patients showed lesion extension on follow-up imaging. The most common extension site was the claustrum. Patients with more lesion extension showed poorer outcomes than those without lesion extension.

Subsequent extratemporal lesion extension was closely associated with poor prognosis in NORSE-LE patients. This study explores a new subtype of NORSE and suggests a possible common underlying pathomechanism between NORSE and LE.