Abstract Details

Title Retrospective Review of 6 Patients with New-Onset Refractory Status Epilepticus (NORSE) Syndrome: Early Intervention with Intravenous Cyclophosphamide May Improve Outcome

Topic Epilepsy

Presentation(s) IN9 - (-)

Poster/Presentation
Number 001

Objective

Background Autoimmune epilepsy is usually resistant to anti-epileptic agents but may respond to immunotherapy. Despite much progress, there remains a group of epileptic syndromes of unknown etiology, presenting as status epilepticus, which is extremely refractory to either anti-epileptic agents or first-line immunotherapy with intravenous high-dose methylprednisolone or immunoglobulins, resulting in a vegetative state or death. This disorder has received several names, including FIRES, DESC, AERRPS, or NORSE. No effective therapy has been reported yet.

Design/Methods A 23-year retrospective review of 6 patients with NORSE (3 men, 3 women, aged 15-38 years), diagnosed between 1989 and 2012. NORSE was defined as new onset status epilepticus in previously healthy adults, highly refractory to antiepileptics and first-line immunotherapy, and without clear etiology. Antibodies to synaptic and neuronal cell surface proteins, including NMDAR, GABABR, AMPAR, Caspr2, Lgi1, and DPPX were examined and found negative in 4 patients (antibodies were not studied in 2 patients diagnosed before 1994).

Results All patients presented with fever, followed by convulsive status epilepticus within 1-14 days (median 4.5), evolving to refractory repetitive partial or generalized seizures without a latent period. MRI showed extensive brain abnormalities involving limbic and extra-limbic regions related to seizure activity. CSF showed mild inflammatory changes without OCBs. Two patients who did not receive immunotherapy died, 2 treated with first-line immunotherapy during acute stage progressed to a vegetative state, and 2 treated with intravenous cyclophosphamide with first-line immunotherapy during acute stage improved although daily partial seizures persisted. Autopsy findings in one patient were non-specific.

Conclusions NORSE is a catastrophic epileptic syndrome with high mortality. Our study suggests that prompt intervention with intravenous cyclophosphamide improves outcome. Cellular rather than humoral immune-mechanisms may be involved in this disorder.

Authors/Disclosures
Juntaro Kaneko PRESENTER	Juntaro Kaneko has nothing to disclose.
Takahiro Iizuka, MD (Department of Neurology, Kitasato University School of Medicine)	The institution of Dr. Iizuka has received research support from EUROIMMUN Japan Co., Ltd.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Junichi Hamada, MD, PhD (Dpet of Neurology, Kitasato University Kitasato Institute Hospital)	No disclosure on file
Josep O. Dalmau, MD, PhD, FAAN	Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas Research Institute of America. Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Research & Development . Dr. Dalmau has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for ��ɫ��. An immediate family member of Dr. Dalmau has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Dalmau has received research support from Sage Therapeutics. The institution of Dr. Dalmau has received research support from Edmond J.Safra Foundation . The institution of Dr. Dalmau has received research support from La Caixa Foundation. The institution of Dr. Dalmau has received research support from Spanish Ministry of Health (ISCIII). The institution of Dr. Dalmau has received research support from Euroimmun, Inc. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care.
Kazutoshi Nishiyama, MD, PhD	Kazutoshi Nishiyama, MD, PhD has nothing to disclose.
	No disclosure on file

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