Claustrum Sign: An Increasingly Recognized Imaging Feature of New-Onset Refractory Status Epilepticus (NORSE)

Abstract

The claustrum sign, marked by increased MRI signal intensity of the claustrum, is an increasingly recognized imaging finding associated with new-onset refractory status epilepticus (NORSE), and may be associated with a more refractory disease course and worse outcomes. We present a 42-year old male patient who developed NORSE refractory to several treatments including immunotherapy, with MRI demonstrating the claustrum sign early in his disease course. We aim to highlight this sign as an important feature of NORSE, which could alert clinicians to the diagnosis, prompting more extensive workup and aggressive treatment earlier on.

A 42-year-old previously healthy male was admitted to hospital with new onset refractory status epilepticus (NORSE). Extensive investigations including three lumbar punctures did not reveal any specific infectious or inflammatory etiology, including autoimmune antibody testing on both serum and cerebrospinal fluid. Initial MRI revealed bilateral mesial temporal lobe changes suggestive of limbic encephalitis, as well as the claustrum sign consistent with NORSE (Figure 1). His seizures remained refractory to 6 antiseizure medications, IV steroids, IVIG, plasma exchange, rituximab and cyclophosphamide, and he remained in a phenobarbital coma for over 60 days. Follow-up MRI at 53 days showed marked cortical atrophy (Figure 2).

Figure 1.

Initial MRI Scan. Increased Signal Intensity in Bilateral Medial Temporal Lobes (left panel). Note Bilateral Claustrum Sign (right panel).

Figure 2.

Follow-Up MRI Scan Obtained 53 Days After Presentation. Note the Interval Development of Medial Temporal Atrophy (left panel), and Global Cortical Atrophy (right panel).

High signal intensity of the bilateral claustrum (“claustrum sign”) is typically associated with pediatric febrile infection-related epilepsy syndrome (FIRES) but can also be seen in adult NORSE. ¹ Other typical MRI features of NORSE include bilateral mesial temporal signal change, diffuse leptomeningeal enhancement, and rapidly progressive cortical atrophy. ² The mesial temporal lobe changes can persist beyond the acute phase and are predictive of worse outcomes overall, ² as seen in our patient. The pathophysiology of the claustrum sign is unknown, but its presence should alert practitioners to the possibility of a more refractive course of disease, including the development of chronic refractory epilepsy, and the need for early aggressive intervention, including immunotherapy. ³