Early initiation of intravenous cyclophosphamide and one-year outcome in super-refractory cryptogenic-new onset refractory status epilepticus

Yasufumi Yorichika; Shuichiro Neshige; Hideaki Sakahara; Narumi Ono; Megumi Nonaka; Yuichiro Tagane; Tomoaki Watanabe; Keisuke Tachiyama; Haruka Ishibashi; Masahiro Nakamori; Takeo Shishido; Shiro Aoki; Hiroki Ueno; Yu Yamazaki; Takahiro Iizuka; Hirofumi Maruyama

doi:10.1002/epi4.13055

Early initiation of intravenous cyclophosphamide and one-year outcome in super-refractory cryptogenic-new onset refractory status epilepticus

Epilepsia Open. 2024 Dec 19. doi: 10.1002/epi4.13055. Online ahead of print.

Authors

Yasufumi Yorichika¹, Shuichiro Neshige^{1

2}, Hideaki Sakahara¹, Narumi Ono¹, Megumi Nonaka¹, Yuichiro Tagane¹, Tomoaki Watanabe¹, Keisuke Tachiyama¹, Haruka Ishibashi¹, Masahiro Nakamori¹, Takeo Shishido³, Shiro Aoki¹, Hiroki Ueno⁴, Yu Yamazaki¹, Takahiro Iizuka⁵, Hirofumi Maruyama^{1

2}

Affiliations

¹ Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
² Epilepsy Center, Hiroshima University Hospital, Hiroshima, Japan.
³ Department of Neurology, Hiroshima North Medical Center Asa Citizens Hospital, Hiroshima, Japan.
⁴ Department of Neurology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.
⁵ Department of Neurology, Kitasato University School of Medicine, Sagamihara, Japan.

PMID: 39701580
DOI: 10.1002/epi4.13055

Abstract

To explore the potential efficacy of early initiation of intravenous cyclophosphamide (IVCPA), we reviewed consecutive four cases of super-refractory cryptogenic-new onset refractory status epilepticus (C-NORSE) between 2015 and 2023. We compared functional outcomes at 3 months and 1 year after the onset between patients who received IVCPA within 20 days (early-treated) and those who received it later (late-treated). All patients (median age: 43 years) had a prodromal fever. Brain MRI revealed symmetrically increased FLAIR signals in the medial temporal lobes of all patients. Despite initiating antiseizure medications (ASMs) and first-line immunotherapy (intravenous-methylprednisolone and immunoglobulins) within a median of 3 days from onset, SE persisted >5 days. The diagnosis of C-NORSE was suggested based on a high C-NORSE score (6/6). Thus, all patients received IVCPA a median of 15.5 days after seizure onset (three within 20 days and one at 31 days). One of the three early-treated patients also received tocilizumab. Early-treated patients exhibited shorter sedation periods (median 29 vs. 75 days) and better 1 year functional status (mRS 1-2 vs. mRS 4) compared to the late-treated patient. Early initiation of IVCPA and/or tocilizumab, along with ASMs, may contribute to a better one-year functional status in super-refractory C-NORSE patients. PLAIN LANGUAGE SUMMARY: This study demonstrates the potential efficacy of early administration of intravenous cyclophosphamide on one-year functional status in patients with super-refractory cryptogenic-new onset refractory status epilepticus. "Early-treated patients" who received it within 20 days of seizure onset achieved a good one-year functional status. The "late-treated patient" (Case 4) who received it later did not achieve a good functional status. Early initiation of cyclophosphamide, along with antiseizure medications, may contribute to a better one-year functional status in this population.

Keywords: NORSE; autoantibodies; brain MRI; immunotherapy.