Supplemental Table 1. Baseline clinical characteristics of 14 patients with severe fever with thrombocytopenia syndrome-associated encephalopathy/encephalitis
SFTS (n=14)Age, mean years ± SD / 65 ± 6
Male gender / 11 (79)
Season (months)
Spring - Summer (3-8) / 7 (50)
Fall (9-11) / 7 (50)
Eschar / 3 (27)
Clinical characteristics
Fever / 14 (100)
Skinrash / 1 (10)
Headache / 12 (86)
Altered mental status / 10 (71)
Seizure / 2 (14)
Underlying disease
Previous healthy / 10 (71)
Diabetes / 1 (10)
Solid tumor / 0
Chronic liver disease / 0
Chronic kidney disease / 0
Immunosuppressive condition† / 0
Leukocytosis (WBC > 10,000 /mm3) / 0
Leukopenia (WBC < 4,000 /mm3) / 10 (71)
Thrombocytopenia (Platelet, < 150 103 /mm3) / 14 (100)
Normal CRP (≤ 1.0 mg/dL) / 12 (86)
Renal dysfunction / 4 (36)
Clinical course
ICU admission / 6 (55)
In-hospital mortality / 3 (21)
Treatment
Doxycycline / 12 (86)
Ribavirin / 5 (36)
Abbreviations: WBC, white blood cell; CRP, C-reactive protein; ICU, intensive care unit
NOTE. Data are no. (%) of patients, unless otherwise indicated.
Supplemental Table 2. Levels of cytokines, chemokines, and viral loadin CSF and plasma samples from 5 patients with SFTS-associated encephalopathy.
Case 8. / Case 9. / Case 10. / Case 11. / Case 12. / Case 14.CSF / Serum / CSF
/Serum / CSF / Serum / CSF
/Serum / CSF / Serum / CSF
/Serum / CSF / Serum / CSF
/Serum / CSF / Serum / CSF
/Serum / CSF / Serum / CSF
/Serum
Real-time RT-PCRa / ND / 6.18 / NA / 3.65 / 7.44 / 10-3.79 / 3.85 / 5.14 / 10-1.29 / 3.76 / 9.51 / 10-5.75 / 4.86 / 7.07 / 10-2.21 / ND / 6.64 / NA
G-CSF, pg/mL / 7.04 / 14.42 / 0.49 / 23.22 / 44.68 / 0.52 / 6.01 / 10.60 / 0.57 / 9.39 / 26.68 / 0.35 / 13.71 / 15.48 / 0.89 / 9.05 / 14.60 / 0.62
GM-CSF, pg/mL / 0.00 / 0.00 / NA / 0.00 / 16.10 / 0.00 / 15.87 / 0.00 / NA / 14.79 / 0.00 / NA / 59.86 / 21.24 / 2.82 / 0.00 / 0.00 / NA
IFN-α, pg/mL / 36.16 / 22.48 / 1.61 / 511.33 / 12304.95 / 0.04 / 4.12 / 3.33 / 1.24 / 169.82 / 10039.57 / 0.02 / 28.49 / 8.56 / 3.32 / 151.34 / 4166.19 / 0.04
IFN-γ, pg/mL / 0.00 / 4.86 / 0.00 / 7.30 / 155.10 / 0.05 / 3.80 / 17.16 / 0.22 / 5.05 / 56.74 / 0.09 / 77.81 / 19.92 / 3.91 / 166.86 / 33.86 / 4.93
TNF, pg/mL / 0.00 / 5.67 / 0.00 / 0.00 / 4.62 / 0.00 / 0.00 / 1.71 / 0.00 / 0.00 / 2.12 / 0.00 / 0.00 / 5.39 / 0.00 / 0.00 / 0.00 / NA
IL-1β, pg/mL / 0.00 / 1.02 / 0.00 / 0.00 / 3.11 / 0.00 / 0.00 / 2.19 / 0.00 / 0.00 / 10.20 / 0.00 / 3.40 / 3.67 / 0.93 / 0.00 / 4.19 / 0.00
IL-6, pg/mL / 17.19 / 26.38 / 0.65 / 21.49 / 146.94 / 0.15 / 36.78 / 89.04 / 0.41 / 26.11 / 172.48 / 0.15 / 111.74 / 110.45 / 1.01 / 12.46 / 52.82 / 0.24
IL-10, pg/mL / 2.39 / 8.95 / 0.27 / 2.39 / 35.01 / 0.07 / 0.00 / 8.24 / 0.00 / 0.00 / 61.37 / 0.00 / 0.00 / 0.00 / NA / 3.19 / 10.49 / 0.30
IL-12p40, pg/mL / 44.37 / 33.73 / 1.32 / 0.00 / 72.45 / 0.00 / 44.37 / 206.58 / 0.21 / 18.09 / 76.81 / 0.24 / 69.11 / 69.11 / 1.00 / 44.37 / 63.51 / 0.70
IL-13, pg/mL / 3.18 / 0.00 / NA / 0.00 / 2.62 / 0.00 / 0.00 / 0.00 / NA / 0.00 / 0.99 / 0.00 / 0.00 / 3.53 / 0.00 / 5.68 / 6.44 / 0.88
IL-17α, pg/mL / 0.00 / 24.94 / 0.00 / 4.48 / 9.07 / 0.49 / 2.61 / 0.00 / NA / 2.05 / 0.58 / 3.52 / 6.14 / 2.98 / 2.06 / 0.00 / 9.44 / 0.00
MCP-1/CCL2, pg/mL / 1062.90 / 52.01 / 20.44 / 6170.95 / 667.04 / 9.25 / 766.68 / 128.06 / 5.99 / 2674.20 / 781.37 / 3.42 / 3086.51 / 378.94 / 8.15 / 1089.81 / 257.05 / 4.24
MIP-1a/CCL3, pg/mL / 10.34 / 8.68 / 1.19 / 9.76 / 16.53 / 0.59 / 11.35 / 10.55 / 1.08 / 9.76 / 34.73 / 0.28 / 0.00 / 6.98 / 0.00 / 9.76 / 12.47 / 0.78
MIP-1β /CCL4, pg/mL / 3.71 / 0.00 / NA / 5.22 / 164.81 / 0.03 / 151.74 / 11.55 / 13.14 / 5.41 / 8.90 / 0.61 / 8.47 / 57.77 / 0.15 / 0.00 / 3.23 / 0.00
RANTES/CCL5, pg/mL / 0.00 / 1838.10 / 0.00 / 0.00 / 2286.12 / 0.00 / 0.00 / 2171.22 / 0.00 / 0.00 / 9929.47 / 0.00 / 5.00 / 987.49 / 0.01 / 36.17 / 16377.75 / 0.00
CXCL8/IL-8, pg/mL / 402.75 / 71.57 / 5.63 / 633.75 / 85.56 / 7.41 / 138.96 / 37.99 / 3.66 / 455.68 / 124.21 / 3.67 / 637.56 / 117.53 / 5.42 / 150.27 / 39.04 / 3.85
IP-10/CXCL10, pg/mL / 5394.13 / 1347.75 / 4.00 / 14861.13 / 11220.53 / 1.32 / 1554.43 / 1062.04 / 1.46 / 10294.89 / 10460.68 / 0.98 / 5447.30 / 2904.96 / 1.88 / 4376.51 / 6427.82 / 0.68
VEGF, pg/mL / 17.04 / 0.00 / NA / 29.42 / 26.78 / 1.10 / 17.67 / 17.88 / 0.99 / 17.46 / 22.82 / 0.77 / 18.96 / 25.55 / 0.74 / 0.00 / 0.00 / NA
Abbreviation: RT-PCR, reverse transcriptase polymerase chain reaction; CSF, cerebrospinal fluid; ND, not detected; NA, not available; G-CSF, granulocyte colony-stimulatingfactor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; MCP, monocyte chemoattractant protein; CCL, chemokine (C-C motif) ligand; RANTES; regulated on activation, normal T cell expressed and secreted; CXCL; chemokine (C-X-C motif) ligand; IP, interferon gamma-induced protein; VEGF, vascular endothelial growth factor
a SFTS viral loads are shown as log10 copies/mL
Supplemental Table 3. Electroencephalography findings in patients with encephalopathy associated with severe fever with thrombocytopenia syndrome encephalopathy.
Case no / Background / Epileptiform discharge1 / The background of both hemispheres was composed of 4-5 Hz theta activity intermixed with 1-2 Hz delta activity which is not reactive to pain stimuli / No epileptiform discharge
4 / 5-7Hz theta rhythm intermixed with delta rhythm / Frequent sharp wave on left frontal area (F3 max)
7 / Theta rhythm frequency: 4-6 Hz / No epileptiform discharge
8 / Theta rhythm frequency: 4 Hz / No epileptiform discharge
9 / Nearly continuous rhythmic or semirhythmic delta slow activity of medium / No epileptiform discharge
10 / Theta rhythm frequenct: 6-7 Hz / No epileptiform discharge
11 / Continuous generalized theta to delta slowing / No epileptiform discharge
12 / Theta rhythm frequenct: 4-7 Hz / No epileptiform discharge
13 / Posterior dominant rhythms: 8.5-11.0 Hz, small amount / No epileptiform discharge