Resolution of cryptogenic new onset refractory status epilepticus with tocilizumab

Abstract

New onset refractory status epilepticus (NORSE) was defined by the International League Against Epilepsy as occurring in patients presenting without a prior diagnosis of epilepsy or other neurological disease, with seizures that persist beyond 24 h. There is still a need to develop new treatment strategies for NORSE, particularly for those patients who are least responsive to conventional medical therapies. We present a case of a young female patient without any medical history presenting with status epilepticus, which was refractory not only to anti-seizure medications and anesthetics, but also to conventional immunomodulatory therapies. After nine weeks of electroclinical seizure activity, the patient responded to two doses of tocilizumab.

Keywords: Interleukin-6; Refractory; Status epilepticus; Tocilizumab.

Fig. 1

MRI Brain, With and Without Contrast: small scattered foci of gradient susceptibility on T2* sequence noted in the gray-white matter junction throughout the right cerebral hemisphere (A, B) and left posterior parietal lobe (B). These are not visualized on FLAIR (C) or T1 post-contrast (D).

Fig. 2

A, B. Biopsy of frontal lobe cortex and subcortical white matter showed a subtle microvasculopathy characterized by fibrinoid thickening of small vessel walls, which were negative for amyloid on Congo red and Beta-amyloid immunostain (not shown) (H&E, A: 200×, B:400×). C. CD68 highlights activated microglia as well as macrophages and hemosiderin deposition in the perivascular spaces indicative of compromise of the blood brain barrier (CD68, 200×). D. Lymphocytes were limited to the perivascular spaces of small vessels with neither extension into the brain parenchyma nor infiltrating vessel walls (CD45, 400×). (Arrowhead: hemosiderin in perivascular spaces; *: lumen of small vessels; white arrow: activated microglia; black arrow: lymphocytes in perivascular spaces).

Fig. 3

Brain MRI Findings. MRI Brain with and without contrast: small scattered foci of gradient susceptibility on T2* sequence noted in the gray-white matter junction throughout the right cerebral hemisphere (Panels A, B) and left posterior parietal lobe (Panel B). These are not visualized on FLAIR (C) or T1 post-contrast (D).

Fig. 4

Histopathological Findings on Brain Biopsy. A and B: Biopsy of frontal lobe cortex and subcortical white matter showed a subtle microvasculopathy characterized by fibrinoid thickening of small vessel walls, which were negative for amyloid on Congo red and Beta-amyloid immunostain (not shown) (H&E, A: 200×, B:400×). Panel C: CD68 highlights activated microglia as well as macrophages and hemosiderin deposition in the perivascular spaces indicative of compromise of the blood brain barrier (CD68, 200x). Panel D: Lymphocytes were limited to the perivascular spaces of small vessels without extension into the brain parenchyma or infiltration of vessel walls (CD45, 400×). (Arrowhead: hemosiderin in perivascular spaces; *: lumen of small vessels; white arrow: activated microglia; black arrow: lymphocytes in perivascular spaces).