Claustrum Involvement in New Onset Refractory Status Epilepticus: A Systematic Review

Abstract

The claustrum sign is a distinctive neuroimaging finding characterized by bilateral T2/FLAIR hyperintensity of the claustrum, one of the most interconnected regions of the human brain. It was first described in new-onset refractory status epilepticus (NORSE) and febrile infection–related epilepsy syndrome (FIRES). A systematic search was conducted according to PRISMA guidelines from 2018 (formal definition of NORSE) to February 2026 (PROSPERO 2026 CRD420261307306). We included peer-reviewed original studies reporting MRI findings and patient-level data, and compared clinical characteristics, treatments, and outcomes of patients with claustrum alteration versus NORSE/FIRES patients without this finding. Of 785 records identified, 65 studies met inclusion criteria; 41 provided individual patient data, yielding 206 NORSE cases (72 with the claustrum sign, 134 without). All but one patient with the claustrum sign met criteria for cryptogenic NORSE. Patients were predominantly young (mean age 24.9 years) and had a febrile prodrome in 93% of cases. Convulsive status epilepticus (SE) occurred in 98%, progressing to super-refractory SE (SRSE) in more than half reported cases. Bilateral claustrum hyperintensity was detected in 68/71 patients during the acute phase, typically emerging 7 days after SE onset. Immunotherapy was administered in 92% of patients. In-hospital mortality was 9%, while 74% of patients developed chronic epilepsy. Compared with patients without claustrum involvement, those with the claustrum sign more often had febrile onset (93% vs. 51%, p < 0.001) and convulsive SE (98% vs. 81.5%, p = 0.008), lower rates of SRSE (51% vs. 96.5%, p < 0.001), and ICU admission (71% vs. 99%, p < 0.001), and a trend toward lower mortality (9% vs. 16%, p = 0.240). Recognition of the claustrum sign may support early diagnosis and targeted treatment.

Trial Registration: PROSPERO 2026 [CRD420261307306]