Objective: To characterize the clinical, EEG, and brain imaging findings in an adult case series of patients with de novo refractory status epilepticus (SE) occurring after a febrile illness.Methods: A retrospective study (2010)(2011)(2012)(2013) was undertaken with the following inclusion criteria: (1) previously healthy adults with refractory SE; (2) seizure onset 0-21 days after a febrile illness; (3) lacking evidence of infectious agents in CSF; (4) no history of seizures (febrile or afebrile) or previous or concomitant neurologic disorder.Results: Among 155 refractory SE cases observed in the study period, 6 patients (17-35 years old) fulfilled the inclusion criteria. Confusion and stupor were the most common symptoms at disease onset, followed after a few days by acute repeated seizures that were uncountable in all but one. Seizures consisted of focal motor/myoclonic phenomena with subsequent generalization. Antiepileptic drugs failed in every patient to control seizures, with all participants requiring intensive care unit admission. Barbiturate coma with burst-suppression pattern was applied in 4 out of 6 patients for 5-14 days. One participant died in the acute phase. In each patient, we observed a reversible bilateral claustrum MRI hyperintensity on T2-weighted sequences, without restricted diffusion, time-related with SE. All patients had negative multiple neural antibodies testing. Four out of 5 surviving patients developed chronic epilepsy.Conclusions: This is a hypothesis-generating study of a preliminary nature supporting the role of the claustrum in postfebrile de novo SE; future prospective studies are needed to delineate the specificity of this condition, its pathogenesis, and the etiology. Neurology ® 2015;85:1224-1232 GLOSSARY ADC 5 apparent diffusion coefficient; AED 5 antiepileptic drug; FIRES 5 febrile infection-related epilepsy syndrome; ICU 5 intensive care unit; IVIg 5 IV immunoglobulin; NORSE 5 new-onset refractory status epilepticus; PEX 5 plasma exchange; SE 5 status epilepticus.In the last 2 decades, several authors described a series of syndromes characterized by the development of a difficult to treat status epilepticus (SE) in previously healthy children after a febrile illness.1-7 The condition is characterized by a refractory SE and followed by drug-resistant epilepsy, with often severe neuropsychiatric sequelae or death. These entities have been identified by different acronyms, but febrile infection-related epilepsy syndrome (FIRES) is the one that best underscores the main features of the disorder.8 Cases with a similar clinical picture have been described also in adults and in these case series the most frequently used definition is new-onset refractory SE (NORSE).9-13 Recently, it was pointed out that different terms probably have been used to describe the same condition.14,15 However, there is no consensus among investigators. Adult cases are more heterogeneous, some with clear similarities with FIRES cases (with only the age at onset as the main difference), other...