Table e-1 Clinical features, CSF, EEG, Initial diagnosis, C-NORSE score, and brain MRI of 11 patients with cryptogenic NORSE

1Status epilepticus severity score at onset of status epilepticus is scored from 0 to 6 for individual patient based on four outcome predictors (age, history of seizures, seizure type, and extent of consciousness

impairment).

2CSF protein level is expressed in mg/dl; 3C-NORSE score is scored from 0-6 (see Table 2); 4Day 1 is defined as the day of onset of epileptic seizure or SE. 5Brain CT is included in follow-up studies.

No./ age, y/ sex/ date of onset, y

Prodromal symptoms/ interval to SE

Main type of SE/ STESS1 /PMH or FH of seizures

CSF: WBC per μL/ Protein2/ OCBs/ IgG index

Main EEG findings Initial suspected diagnosis/ C-NORSE score3

Initial brain MRI findings4/ subsequent changes/ at last follow-up (day of study)5

1/ 19/ F/ 2001

Fever/ 4 days

SGCSE/ 3/ none 4/ 61/ −/ n.d. Diffuse slow, multifocal SWA

AE/ 5

NR (day 1, 2)/ mild DBA (day 30, 73); CA (39 months)/ DBA became less clear but CA remained (110 m)

2/ 47/ M/ 2008

Fever/ 14 days

SGCSE/ 3/ yes, FH of seizure in daughter

17/ 76/ −/ n.d. Multifocal SWA with/without focal component

NMDARE/ 5

NR (day 1)/ not available/ DBA (6 m)

3/ 17/ M/ 2010

Fever, HA/ 4 days

SGCSE/ 2/ yes, PMH of FC, FH of FC in elder sister

6/ 34/ −/ 0.47 Bisynchronous SWA with/without focal component

NMDARE/ 6

NR (day 1)/ symmetric increased medial T T2/FLAR signal (day 6); extensive increased DWI/T2/FLAIR signal in medial T, insula, claustrum, and opercular cortex (day 20); increased signal improved but mild DBA developed (day 67)/ mild DBA (62 m)

4/ 30/ F/ 2011

Fever, HA/ 4 days

SGCSE/ 3/ none 224 (mono: 8%)/ 77/ −/ 0.52

Bisynchronous SWA with/without focal component

NMDARE/ 6

NR (day 1)/ symmetric increased DWI/FRAIR signal in medial T, insula, and thalamus (day 6, 15, 23, 68); marked DBA (5, 9 m)/ DBA (15 m)

5/ 23/ F/ 2011

Fever, HA/ 5 days

SGCSE/ 3/ none 1/ 42/ n.d./ n.d. Bisynchronous SWA with/without focal component

ALE/ 6

NR (day 1)/ symmetric increased T2/FLAIR signal in medial T and claustrum (day 12);increased signal remained but DBA developed (day 34)/ no marked DBA (6.5 m)

6/ 27/ F/ 2013

Fever/ 4 days

SGCSE/ 3/ none 103 (mono: 68%)/ 73/ −/ n.d.

Multifocal SWA with/without focal component

NORSE or AE/ 6

NR (day 1)/ symmetric increased T2/FLAIR signal in hippocumpus, claustrum, and opercular cortex (day 3)/ increased signal remained but no apparent DBA (day 60)

7/ 39/ M/ 2015

Nonspecific/ 7 days

SGCSE/ 3/ none 2/ 33/ −/ 0.83 Diffuse slowing, SWA, PSD

NORSE or AE/ 5

NR (day 1)/ symmetric increased DWI/FLAIR signal in medial T, hippocampus, insula and cerebellum (day 3, 8); DBA and CA (day 21, 42)/ marked DBA (day 63).

8/ 18/ M/ 2015

Fever/ 4 days

SGCSE/ 3/ none 12/ 41/ −/ 0.53 Bisynchronous SWA AE / 5

NR (day 4)/ unremarkable (day 14, 41)/ unremarkable (7 m)

9/ 20/ F/ 2016

Fever, HA/ 6 days

SGCSE/ 3/ yes, FH of FC in elder brother

4/ 53/ −/ 0.52 Bisynchronous SWA with/without focal component

NORSE or AE/ 6

NR (day 1, 4)/ symmetric increased FLAIR signal in insula and diffuse cerebral cortex (day 25); more prominent signal in insula, basal ganglia, and opercular cortex (day 74); increased signal resolved but DBA developed (day 92)/ marked DBA with CA (5 m, 15 m)

10/ 37/ M/ 2016

Fever, HA / 6 days

SGCSE/ 3/ none 18/ 28/ −/ 0.57 Bisynchronous SWA with/without focal component

NORSE or ALE/ 6

NR (4 days prior to onset of SE)/ symmetric increased T2/FLAIR signal in medial T, hippocampus, insula (day 5); prominent increased T2/FLAIR signal in medial T, insula, claustrum, external capsule, and basal ganglia (day 13); less prominent increased signal (day 25, 38); mild DBA (day 58)/ No increased signal (6 m)

11/ 59/ F/ 2016

Fever, HA / 6 days

SGCSE/ 3/ none 5/ 61/ −/ 0.49 Bisynchronous SWA, PSD, with/without focal component

NORSE or AE/ 6

NR (day 1)/ symmetric increased T2/FLAIR signal in hippocampus and claustrum (day 8, 25); increased signal improved but medial T atrophy developed (day 38)/ T atrophy (day 99)

AE: autoimmune encephalitis; ALE: autoimmune limbic encephalitis; CA: cerebellar atrophy; C-NORSE: cryptogenic new-onset refractory status epilepticus (NORSE); CSF: cerebrospinal fluid; DBA: diffuse brain

atrophy; F: female; FC: febrile convulsion; FH: family history; FLAIR: fluid-attenuated inversion recovery; HA: headache; M: male; m: month(s); mono: mononuclear cells; MRI: magnetic resonance imaging; n.d.:

not done; NMDARE: anti-NMDA receptor encephalitis; NR: not revealing; NSA-antibodies: autoantibodies against neuronal cell surface antigens and synaptic proteins; OCBs: oligoclonal bands; PMH: past medical

history; PSD: periodic epileptiform discharges; SE: status epilepticus; SGCSE: secondarily generalized convulsive status epilepticus; STESS: status epilepticus severity score; T: temporal lobe; SWA: spike-and-wave

activity; WBC: white blood cells; y: year(s).