In adult patients who are comatose after return of spontaneous circulation (ROSC), the following indices predict good neurological outcome (no, or mild to moderate neurological disability) with > 80% specificity and > 40% sensitivity in most studies: | |
• a withdrawal or localisation motor response to pain immediately or at 72–96 h after ROSC | |
• normal blood values of neuron specific enolase (NSE) at 24h–72 h after ROSC | |
• a short-latency somatosensory evoked potentials (SSEPs) N20 wave amplitude > 4 µV or a continuous background without discharges on electroencephalogram (EEG) within 72 h from ROSC | |
• absent diffusion restriction in the cortex or deep grey matter on diffusion weighted imaging (DWI) of brain magnetic resonance imaging on days 2–7 after ROSC | |
Most studies had moderate or high risk of bias, mainly from selection or confounding. |
Introduction
Methods
Population, intervention, comparator, outcome, time frame and study design (PICOST) framework
Eligibility criteria
Patient population
Interventions (Index tests)
Outcome
Study design
Study type
Search strategy
Data extraction
Evidence appraisal
Data analysis
Results
Study selection
Study characteristics
Author, year | Study design | Country | Enrolment period | N. pts | Age, mean [SD] or median (IQR) | Males, n (%) | VF/pVT, n (%) | OHCA % | TTM % | Index test | Timing outcome |
---|---|---|---|---|---|---|---|---|---|---|---|
Clinical examination | |||||||||||
Hifumi, 2015 [20] | Retrospective | Japan | 2005–2009 | 302 | – | 244 (80.8) | 238 (78.8) | 100 | 100 | MR | 3 months |
Moseby-Knappe, 2020 [21] | Retrospective | International | 2010–2013 | 585 | 64 (56–72) | 479 (81.9) | 473 (80.9) | 100 | 100 | MR | 6 months |
Biomarkers | |||||||||||
Moseby-Knappe, 2021 [22] | Retrospective | International | 2010–2013 | 717 | 65 (56–73) | 580 (80.9) | 558 (77.8) | 100 | 100 | NSE, S100B, NFL, GFAP, Tau protein, UCH-L1 | 6 months |
Streitberger, 2017a [23] | Retrospective | Europe | 2005–2014 | 1053 | 64 [19] | 790 (75) | 621 (59) | 78.3 | 100 | NSE | ICU discharge |
Wihersaari, 2021 [24] | Prospective | Finland and Denmark | 2016–2017 | 112 | 62 (53–68) | 92 (82.1) | N/A | 100 | 100 | NFL | 6 months |
Zellner, 2013 [25] | Retrospective | Germany | 2007–2012 | 123 | 63 [14] | 98 (79.7) | 81 (65.9) | 89.4 | 100 | NSE, NSE decrease | 6 months |
Electrophysiology | |||||||||||
Admiraal, 2019 [26] | Prospective | The Netherlands | 2015–2018 | 149 | 62.2 [1.6]* | 117 (78.5) | 105 (70.5) | 88.6 | 100 | cEEG | 6 months |
Alvarez, 2015 [27] | Prospective | USA | 2013–2014 | 18 | 54 [18] | 9 (50) | 10 (55.6) | N/A | 100 | cEEG | HD |
Backman, 2018 [28] | Prospective | Europe and Australia | 2010–2013 | 207 | 63 (56–70) | 175 (84.5) | N/A | 100 | 100 | EEG | 6 months |
Beretta, 2019 [29] | Prospective | Italy | 2011–2016 | 166 | 61 (51–71) | 120 (72.3) | N/A | 67.5 | 89.2 | EEG | 6 months |
Carrai, 2016 [30] | Retrospective | Italy | 2007–2014 | 167 | 59.8 [17.6] | 106 (63.5) | 72 (43.1) | 80.2 | 100 | EEG | 6 months |
Carrai, 2021 [21] | Retrospective | Italy | 2014–2017 | 41 | 66.5 [3.2]* | 23 (56.1) | 18 (43.9) | 53.7 | 61 | EEG | 6 months |
Duez, 2019 [32] | Prospective | Denmark, Norway | 2013–2013 | 120 | 60 (53–68) | 107 (89.2) | 104 (86.7) | 100 | 100 | EEG | 6 months |
Eertmans, 2019 [33] | Prospective | Belgium | 2011–2014 | 63 | 64 [2]* | 50 (79.4) | 45 (71.4) | 100 | 100 | BIS-EEG | 6 months |
Endisch, 2015 [34] | Prospective | Germany | 2009–2014 | 293 | 64 (53–73) | 205 (70) | 126 (43) | N/A | 100 | SSEP | ICU discharge |
Endisch, 2016 [35] | Prospective | Germany | 2009–2014 | 302 | 64 (53–73) | 209 (69.2) | 130 (43) | N/A | 100 | SSEP HFO burst | ICU discharge |
Glimmerveen, 2020 [36] | Prospective | The Netherlands | 2010–2011; 2012–2018 | 138 | 66.5 [0.95]* | 104 (75.4) | 132 (95.7) | N/A | 100 | SSEP voltage | 6 months |
Hofmeijer, 2015 [37] | Prospective | The Netherlands | 2010–2014; 2012–2014 | 277 | 64 [3]* | 199 (71.8) | 197 (71.1) | 87.7 | 89.2 | cEEG | 6 months |
Lamartine, 2016 [38] | Retrospective | Belgium | 2008–2014 | 92 | 63 (54–76) | 65 (70.7) | 48 (52.2) | 59.8 | 100 | cEEG | 3 months |
Leao, 2015 [39] | Prospective | Portugal | 2012–2014 | 67 | 62.6 [13] | 49 (73.1) | 28 (41.8) | 68.7 | 100 | EEG | 6 months |
Leary, 2010 [40] | Prospective | USA | 2007–2009 | 62 | 55 [16] | 36 (58.1) | 25 (40.3) | 51.6 | 100 | BIS | HD |
Oh, 2013 [41] | Prospective | South Korea | 2010–2011 | 55 | 50 [17.3] | 33 (60) | 20 (36.4) | N/A | 100 | aEEG | HD |
Park, 2018 [42] | Prospective | South Korea | 2014–2017 | 65 | 55.6 [16.8] | 49 (75.4) | 15 (23.1) | 100 | 100 | BIS | 6 months |
Rossetti, 2017 [43] | Prospective | Switzerland, USA | 2009–2016; 2009–2014 | 357 | 61.6 [0.74]* | 265 (74.2) | 250 (70) | N/A | 100 | Video cEEG | 3 months |
Rundgren, 2010a [44] | Prospective | Sweden | 2004–2008 | 95 | 65 (50–74) | 68 (71.6) | 57 (60) | 86.3 | 100 | aEEG | 6 months |
Scarpino, 2021 [45] | Retrospective | Italy | 2016–2018 | 403 | 69 (58–68) | 272 (67.5) | 180 (44.7) | 73.7 | 41.7 | EEG, SSEP | 6 months |
Seder, 2010 [46] | Prospective | USA | 2005–2009 | 83 | 62 (48–72) | 54 (65.1) | 52 (62.7) | N/A | 100 | BIS | HD |
Sivaraju, 2015 [47] | Prospective | USA | 2011–2014 | 100 | 61.9 [2.6]* | 59 (59) | 33 (33) | N/A | 100 | EEG | HD |
Sondag, 2017 [48] | Prospective | The Netherlands | 2010–2015; 2012–2015 | 384 | 61.6 [0.7]* | 283 (73.7) | 283 (73.7) | 89.8 | 100 | EEG | 6 months |
Tjepkema-Cloostermans, 2013 [49] | Prospective | The Netherlands | 2010–2013 | 53 | 60.3 [2.5]* | 39 (73.6) | 31 (58.5) | 86.8 | 100 | EEG | 6 months |
Wennervirta, 2009 [50] | Prospective | Finland | N/A | 30 | 52.8 [2.6]* | 24 (80) | 30 (100) | 100 | 100 | EEG | 6 months |
Westhall, 2016 [51] | Prospective | International | 2010–2013 | 103 | 67 [10] | 80 (77.7) | 74 (71.8) | 100 | 100 | EEG | 6 months |
Imaging | |||||||||||
Lee, 2017 [52] | Retrospective | South Korea | 2012–2014 | 67 | 56.3 [16.9] | 49 (73.1) | 12 (17.9) | 100 | 100 | CT | 1 months |
Mlynash, 2010a [53] | Prospective | USA | 2006–2009 | 33 | 55.8 [1.7]* | 24 (72.7) | N/A | 72.7 | 63.6 | DW-MRI | 6 months |
Park, 2020 [54] | Retrospective | Korea | 2018–2019 | 36 | 52.9 [15.9] | 26 (72.2) | 14 (38.9) | 100 | 100 | DW-MRI | 6 months |
Multimodal | |||||||||||
Jang, 2019 [55] | Retrospective | South Korea | 2016–2018 | 39 | 52.3 [17] | 15 (38.5) | N/A | N/A | 100 | Continuous aEEG, MRI | 6 months |
Oh, 2019 [56] | Retrospective | South Korea | 2009–2017 | 192 | 54.3 [16.3] | 130 (67.7) | 58 (30.2) | 89.6 | 100 | SSEP, DW-MRI | 6 months |
Author, year | Sample size, n | Index value | Timing | Timing outcome | TP | FP | FN | TN | Sensitivity % [95% CI] | Specificity % [95% CI] | LR + [95% CI] |
---|---|---|---|---|---|---|---|---|---|---|---|
GCS Motor score | |||||||||||
Hifumi, 2015 [20] | 302 | 4–5 | Admission | 3 months | 20 | 3 | 153 | 126 | 11.6 [7.2–17.3] | 97.7 [93.4–99.5] | 5 [1.5–16.4] |
Moseby-Knappe, 2020 [21] | 342 | 4–5 | 72–96 h | 6 months | 75 | 39 | 23 | 205 | 76.5 [66.9–84.5] | 84.0 [78.8–83.4] | 4.8 [3.5–6.5] |
Author, year | Sample size, n | Threshold value, µg/L | Timing | Timing outcome | TP | FP | FN | TN | Sensitivity % [95% CI] | Specificity % [95% CI] | LR + [95% CI] |
---|---|---|---|---|---|---|---|---|---|---|---|
3.1 Neuron specific enolase (NSE) | |||||||||||
Zellner, 2013 [25] Moseby-Knappe, 2021 [22] | 103 650 | < 17 ≤ 17 | 24 h | 6 months 6 months | 13 153 | 6 48 | 37 177 | 47 272 | 26 [14.6–40.3] 46.4 [40.9–51.9] | 88.7 [77–95.7] 85 [80.6–88.7] | 2.3 [0.9–5.6] 3.1 [2.3–4.1] |
Zellner, 2013 [25] Moseby-Knappe, 2021 [22] | 84 614 | < 18.1 ≤ 17 | 48 h | 6 months 6 months | 15 186 | 5 48 | 22 136 | 42 244 | 40.5 [24.8–57.9] 57.8 [52.2–63.2] | 89.4 [76.9–96.5] 83.6 [78.8–87.6] | 3.8 [1.5–9.5] 3.5 [2.7–4.6] |
Moseby-Knappe, 2021 [22] Streitberger, 2017a [23] | 572 1053 | ≤ 17 ≤ 17 | 72 h | 6 months ICU discharge | 230 192 | 52 16 | 77 394 | 213 451 | 74.9 [69.7–79.7] 32.8 [29–36.7] | 80.4 [75.1–85] 96.6 [94.5–98] | 3.8 [3–4.9] 9.6 [5.8–15.7] |
3.2 S-100B protein | |||||||||||
Zellner, 2013 [25] | 114 | < 0.61 | Admission | 6 months | 18 | 6 | 40 | 50 | 31 [19.5–44.5] | 89.3 [78.1–96] | 2.9 [1.2–6.8] |
Zellner, 2013 [25] Moseby-Knappe, 2021 [22] | 110 649 | < 0.12 < 0.105 | 24 h | 6 months 6 months | 20 228 | 6 83 | 34 101 | 50 237 | 37 [24.3–51.3] 69.3 [64–74.2] | 89.3 [78.1–96] 74.1 [68.9–78.8] | 3.5 [1.5–8] 2.7 [2.2–3.3] |
Moseby-Knappe, 2021 [22] | 617 | < 0.105 | 48 h | 6 months | 238 | 82 | 87 | 210 | 73.2 [68.1–78] | 71.9 [66.4–77] | 2.6 [2.1–3.2] |
Moseby-Knappe, 2021 [22] | 578 | < 0.105 | 72 h | 6 months | 254 | 97 | 59 | 168 | 81.2 [76.4–85.3] | 63.4 [57.3–69.2] | 2.2 [1.9–2.6] |
Author, year | Sample size, n | Threshold value, pg/mL | Timing | Timing outcome | TP | FP | FN | TN | Sensitivity % [95% CI] | Specificity % [95% CI] | LR + [95% CI] |
---|---|---|---|---|---|---|---|---|---|---|---|
3.3 Neurofilament light chain (NFL) | |||||||||||
Wihersaari, 2021 [24] Moseby-Knappe, 2021 [22] Wihersaari, 2021 [24] | 107 692 107 | < 30 < 55b < 100 | 24 h | 6 months 6 months 6 months | 55 228 68 | 0 16 5 | 15 123 2 | 37 325 32 | 78.6 [67.1–87.5] 65 [59.7–69.9] 97.1 [90.1–99.7] | 100 [92.2–100] 95.3 [92.5–97.3] 86.5 [71.2–95.5] | - 13.8 [8.5–22.5] 7.2 [3.2–16.2] |
Wihersaari, 2021 [24] Moseby-Knappe, 2021 [22] Wihersaari, 2021 [24] | 109 658 109 | < 30 < 55b < 250 | 48 h | 6 months 6 months 6 months | 54 181 72 | 0 13 5 | 19 156 1 | 36 308 31 | 74 [62.4–83.5] 53.7 [48.2–59.1] 98.6 [92.6–100] | 100 [92–100] 96 [93.2–97.8] 86.1 [70.5–95.3] | - 13.3 [7.7–22.8] 7.1 [3.1–16] |
Wihersaari, 2021 [24] Moseby-Knappe, 2021 [22] Wihersaari, 2021 [24] | 103 608 103 | < 27 < 55b < 300 | 72 h | 6 months 6 months 6 months | 48 164 68 | 0 10 4 | 22 159 2 | 33 275 29 | 68.6 [56.4–79.1] 50.8 [45.2–56.4] 97.1 [90.1–99.7] | 100 [91.3–100] 96.5 [93.6–98.3] 87.9 [71.8–96.6] | - 14.5 [7.8–26.9] 8 [3.2–20.1] |
3.4 Glial fibrillary acidic protein (GFAP) | |||||||||||
Moseby-Knappe, 2021 [22] | 689 | < 22 | 24 h | 6 months | 141 | 11 | 205 | 332 | 40.8 [35.5–46.1] | 96.8 [94.3–98.4] | 12.7 [7–23] |
Moseby-Knappe, 2021 [22] | 654 | < 22 | 48 h | 6 months | 118 | 9 | 216 | 311 | 35.3 [30.2–40.7] | 97.2 [94.7–98.7] | 12.6 [6.5–24.3] |
Moseby-Knappe, 2021 [22] | 599 | < 22 | 72 h | 6 months | 140 | 14 | 175 | 270 | 44.4 [38.9–50.1] | 95.1 [91.9–97.3] | 9 [5.3–15.2] |
3.5 Tau protein | |||||||||||
Moseby-Knappe, 2021 [22] | 694 | ≤ 1.55 | 24 h | 6 months | 100 | 22 | 253 | 319 | 28.3 [23.7–33.3] | 93.5 [90.4–95.9] | 4.4 [2.8–6.8] |
Moseby-Knappe, 2021 [22] | 661 | ≤ 1.55 | 48 h | 6 months | 140 | 16 | 199 | 306 | 41.3 [36–46.7] | 95 [92.1–97.1] | 8.3 [5–13.6] |
Moseby-Knappe, 2021 [22] | 611 | ≤ 1.55 | 72 h | 6 months | 168 | 20 | 157 | 266 | 51.7 [46.1–57.2] | 93 [89.4–95.7] | 7.4 [4.8–11.4] |
3.6 Ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) | |||||||||||
Moseby-Knappe, 2021 [22] | 693 | < 327 | 24 h | 6 months | 222 | 51 | 126 | 294 | 63.8 [58.5–68.8] | 85.2 [81–88.8] | 4.3 [3.3–5.6] |
Moseby-Knappe, 2021 [22] | 663 | < 327 | 48 h | 6 months | 251 | 59 | 89 | 264 | 73.8 [68.8–78.4] | 81.7 [77.1–85.8] | 4 [3.2–5.1] |
Moseby-Knappe, 2021 [22] | 610 | < 327 | 72 h | 6 months | 288 | 84 | 39 | 199 | 88.1 [84.1–91.4] | 70.3 [64.6–75.6] | 3 [2.5–3.6] |
Author, year | Sample size, n | Threshold value, µV | Timing | Timing outcome | TP | FP | FN | TN | Sensitivity % [95% CI] | Specificity % [95% CI] | LR + [95% CI] |
---|---|---|---|---|---|---|---|---|---|---|---|
4.1 SSEP amplitude | |||||||||||
Scarpino, 2021 [45] | 218 | > 3 | 12 h | 6 months | 52 | 15 | 33 | 118 | 61.2 [50–71.6] | 88.7 [82.1–93.5] | 5.4 [3.3–9] |
Scarpino, 2021 [45] | 218 | > 4 | 6 months | 41 | 12 | 44 | 121 | 48.2 [37.3–59.3] | 91 [84.8–95.3] | 5.3 [3–9.6] | |
Scarpino, 2021 [45] | 218 | > 5.3 | 6 months | 22 | 1 | 63 | 132 | 25.9 [17–36.5] | 99.2 [95.9–100] | 34.4 [4.7–250] | |
Scarpino, 2021 [45] | 218 | > 10 | 6 months | 5 | 0 | 80 | 133 | 5.9 [1.9–13.2] | 100 [97.8–100] | - | |
Scarpino, 2021 [45] | 260 | > 4 | 24 h | 6 months | 44 | 14 | 45 | 153 | 49.4 [38.7–60.2] | 89.5 [83.9–93.6] | 4.7 [2.9–7.6] |
Scarpino, 2021 [45] | 260 | > 5 | 6 months | 33 | 12 | 56 | 159 | 37.1 [27.1–48] | 93 [88.1–96.3] | 5.3 [2.9–9.7] | |
Scarpino, 2021 [45] | 260 | > 8 | 6 months | 14 | 5 | 75 | 166 | 15.7 [8.9–25] | 97.1 [93.3–99] | 5.4 [2–14.5] | |
Oh, 2019 [56] | 192 | > 2.31 | 48–72 h | 6 months | 27 | 5 | 24 | 136 | 52.9 [38.5–67.1] | 96.5 [91.9–98.8] | 15 [6.1–36.7] |
Glimmerveen, 2020 [36] | 129 | > 3.6 | 6 months | 10 | 4 | 21 | 94 | 32.3 [16.7–51.4] | 95.9 [89.9–98.9] | 7.9 [2.7–23.4] | |
Oh, 2019 [56] | 192 | > 5.04 | 6 months | 5 | 0 | 46 | 141 | 9.8 [3.3–21.4] | 100 [97.9–100] | - | |
Scarpino, 2021 [45] | 240 | > 4 | 72 h | 6 months | 39 | 23 | 38 | 140 | 50.6 [39–62.2] | 85.9 [79.6–90.8] | 3.6 [2.3–5.6] |
Scarpino, 2021 [45] | 240 | > 6.2 | 6 months | 19 | 12 | 58 | 151 | 24.7 [15.6–35.8] | 92.6 [87.5–96.1] | 3.3 [1.7–6.6] | |
Scarpino, 2021 [45] | 240 | > 9 | 6 months | 11 | 4 | 66 | 159 | 14.3 [7.4–24.1] | 97.5 [93.8–99.3] | 5.8 [1.9–17.7] | |
Endisch, 2015 [34] | 293 | > 4.197 | 24–96 h | ICU discharge | 39 | 12 | 103 | 139 | 27.5 [20.3–35.6] | 92.1 [86.5–95.8] | 3.5 [1.9–6.3] |
Endisch, 2015 [34] | 293 | > 7.194 | ICU discharge | 13 | 4 | 129 | 147 | 9.2 [5–15.1] | 97.4 [93.4–99.3] | 3.5 [1.1–10.3] |
Author, year | Sample size, n | Index | Timing | Timing outcome | TP | FP | FN | TN | Sensitivity % [95% CI] | Specificity % [95% CI] | LR + [95% CI] |
---|---|---|---|---|---|---|---|---|---|---|---|
4.2 SSEP – HFO burst | |||||||||||
Endisch, 2016 [35] | 302 | Early HFO burst present | 24–96 h | ICU discharge | 81 | 65 | 58 | 98 | 58.3 [49.6–66.6] | 60.1 [52.2–67.7] | 1.5 [1.2–1.8] |
Endisch, 2016 [35] | 302 | Late HFO burst present | ICU discharge | 63 | 32 | 76 | 131 | 45.3 [36.9–54] | 80.4 [73.4–86.2] | 2.3 [1.6–3.3] | |
Endisch, 2016 [35] | 302 | Late HFO burst amplitude > 70 nV | ICU discharge | 36 | 21 | 103 | 142 | 25.9 [18.8–34] | 87.1 [81–91.8] | 2 [1.3–3.3] | |
Endisch, 2016 [35] | 302 | Late HFO burst amplitude > 120 nV | ICU discharge | 22 | 7 | 117 | 156 | 15.8 [10.2–23] | 95.7 [91.4–98.3] | 3.7 [1.6–8.4] |
Author, year | Sample size, n | Definition | Timing | Timing outcome | TP | FP | FN | TN | Sensitivity % [95% CI] | Specificity % [95% CI] | LR + [95% CI] |
---|---|---|---|---|---|---|---|---|---|---|---|
5A Continuous or nearly continuous background without discharges | |||||||||||
5A.1 Normal voltage | |||||||||||
5A.1a No unequivocal electrographic seizures, or abundant (> 50%) periodic discharges or abundant spike-wave | |||||||||||
Admiraal, 2019 [26] Admiraal, 2019 [26] | 66 141 | a | 12 h 24 h | 6 months 6 months | 24 63 | 5 22 | 14 12 | 23 44 | 63.2 [46–78.2] 84 [73.7–91.4] | 82.1 [63.1–93.9] 66.7 [54–77.8] | 3.5 [1.5–8.1] 2.5 [1.8–3.6] |
Duez, 2019 [32] Duez, 2019 [32] Westhall, 2016 [51] | 120 44 103 | b | 24 h 48 h 77 (53–102) h | 6 months 6 months 6 months | 33 11 8 | 0 2 0 | 52 13 19 | 35 18 76 | 38.8 [28.4–50] 45.8 [25.6–67.2] 29.6 [13.8–50.2] | 100 [91.8–100] 90 [68.3–98.8] 100 [96.1–100] | – 4.6 [1.1–18.3] – |
Backman, 2018 [28] Westhall, 2016 [51] | 207 103 | c | 76 (62–104) h 77 (53–102) h | 6 months 6 months | 51 13 | 28 1 | 15 14 | 113 75 | 77.3 [65.3–86.7] 48.1 [28.7–68.1] | 80.1 [72.6–86.4] 98.7 [92.9–100] | 3.9 [2.7–5.6] 36.6 [5–266.6] |
5A.1b No seizures or generalised periodic discharges | |||||||||||
Sondag, 2017 [48] Duez, 2019 [32] Hofmeijer, 2015 [37] Duez, 2019 [32] Hofmeijer, 2015 [37] Hofmeijer, 2015 [37] | 248 120 230 44 187 97 | d | 12 h 24 h 24 h 48 h 48 h 72 h | 6 months 6 months 6 months 6 months 6 months 6 months | 63 48 91 15 90 47 | 15 1 22 4 44 24 | 60 37 26 9 4 1 | 110 34 91 16 49 25 | 51.2 [42–60.3] 56.5 [45.3–67.2] 77.8 [69.2–84.9] 62.5 [40.6–81.2] 95.7 [89.5–98.8] 97.9 [88.9–99.9] | 88 [81–93.1] 97.1 [85.1–99.9] 80.5 [72–87.4] 80 [56.3–94.3] 52.7 [42.1–63.1] 51 [36.3–65.6] | 4.3 [2.6–7.1] 19.8 [2–8-137.6] 4 [2.7–5.9] 4.6 [1.1–18.3] 2 [1.6–2.5] 2 [1.5–2.7] |
5A.2 Normal or low voltage | |||||||||||
Carrai, 2021 [31] Carrai, 2016 [30] Scarpino, 2021 [45] Carrai, 2016 [30] | 41 38 218 65 | e | < 6 h 6–12 h 12 h 18–24 h | 6 months 6 months 6 months 6 months | 12 10 48 19 | 1 1 3 6 | 5 1 37 0 | 23 26 130 40 | 70.6 [44–89.7] 90.9 [58.7–99.8] 56.5 [45.3–67.2] 100 [85.4–100] | 95.8 [78.9–99.9] 96.3 [81–99.9] 97.7 [93.5–99.5] 87 [73.7–95.1] | 17 [2.4–118] 24.5 [3.6–169] 25 [8–77.8] 7 [3.4–14.4] |
Rossetti, 2017 [43] Rossetti, 2017 [43] | 357 357 | f | ≤ 48 h 48–72 h | 3 months 3 months | 137 163 | 22 31 | 43 17 | 155 146 | 76.1 [69.2–82.1] 90.6 [85.3–94.4] | 87.6 [81.8–92.0] 82.5 [76.1–87.8] | 6.1 [4.1–9.1] 5.2 [3.7–7.1] |
Carrai, 2016 [30] | 64 | e | 48–72 h | 6 months | 12 | 9 | 0 | 43 | 100 [77.9–100] | 82.7 [69.7–91.8 | 5.4 [3–9.6] |
5A.3 Continuous, nearly continuous, or discontinuous, normal voltage | |||||||||||
Sivaraju, 2015 [47] | 89 | g | ≤ 72 h | HD | 23 | 2 | 9 | 55 | 71.9 [53.3–86.3] | 96.5 [87.9–99.6] | 20.5 [5.2–81.3] |
Sivaraju, 2015 [47] | 89 | h | ≤ 72 h | HD | 25 | 10 | 0 | 54 | 100 [88.7–100] | 84.4 [73.1–92.2] | 6.1 [3.5–10.6] |
Beretta, 2019 [29] | 166 | i | Day 0–5 | 6 months | 54 | 22 | 16 | 74 | 77.1 [65.6–86.3] | 77.1 [67.4–85] | 3.4 [2.3–5] |
5B Other favourable EEG patterns or grading scales | |||||||||||
Lamartine, 2016 [38] Lamartine, 2016 [38] | 29 55 | j | 0–8 h 8–16 h | 3 months 3 months | 6 12 | 5 15 | 1 1 | 17 27 | 85.7 [42.1–99.6] 92.3 [64–99.8] | 77.3 [54.6–92.2] 64.3 [48–78.4] | 3.8 [1.6–8.6] 2.6 [1.7–4] |
Lamartine, 2016 [38] Lamartine, 2016 [38] | 89 80 | 16–24 h 24–48 h | 3 months 3 months | 24 23 | 20 18 | 2 1 | 43 38 | 92.3 [74.9–99.1] 95.8 [78.9–99.9] | 68.3 [55.3–79.4] 67.9 [54–79.7] | 2.9 [2–4.2] 3 [2–4.4] | |
Leao, 2010 [40] | 67 | k | ≤ 24 h after RW | 6 months | 9 | 5 | 3 | 50 | 75 [42.8–94.5] | 90.9 [80–97] | 8.2 [3.4–20.2] |
Alvarez, 2015 [27] Alvarez, 2015 [27] | 18 17 | l | ≤ 24 h 24–48 h | HD HD | 2 7 | 0 2 | 6 1 | 10 7 | 25 [3.2–65.1] 87.5 [47.3–99.7] | 100 [74.1–100] 77.8 [40–97.2] | – 3.9 [1.1–13.7] |
5C Continuous or discontinuous—reduced montage or amplitude-integrated EEG | |||||||||||
Wennervirta, 2009 [50] Wennervirta, 2009 [50] | 30 30 | m | < 24 h 24–48 h | 6 months 6 months | 14 20 | 4 3 | 7 1 | 5 6 | 66.7 [43–85.4] 95.2 [76.2–99.9] | 55.6 [21.2–86.3] 66.7 [29.9–92.5] | 1.5 [0.7–3.3] 2.9 [1.1–7.2] |
Jang, 2019 [55] | 39 | n | ≤ 72 h | 6 months | 12 | 4 | 0 | 23 | 100 [77.9–100] | 85.2 [66.3–95.8] | 6 [2.5–14] |
Oh, 2013 [41] Oh, 2013 [41] | 55 55 | o | ≤ 72 h ≤ 72 h | HD HD | 16 17 | 1 3 | 12 11 | 26 24 | 57.1 [37.2–75.5] 60.7 [40.6–78.5] | 96.3 [81–99.9] 88.9 [70.8–97.6] | 15.4 [2.2–108] 5.5 [1.8–16.5] |
Rundgren, 2010r [44] Rundgren, 2010r [44] | 93 95 | p | 8 (5–14) h 24–48 h | 6 months 6 months | 29 54 | 3 8 | 26 3 | 35 30 | 52.7 [38.8–66.3] 94.7 [85.4–98.9] | 92.1 [78.6–98.3] 78.9 [62.7–90.4] | 6.7 [2.2–20.4] 4.5 [2.4–8.3] |
Eertmans, 2019 [33] Eertmans, 2019 [33] Eertmans, 2019 [33] | 60 57 56 | q | 6–12 h 18–24 h 36–48 h | 6 months 6 months 6 months | 17 19 24 | 6 6 6 | 14 9 4 | 23 23 22 | 54.8 [36–72.7] 67.9 [47.6–84.1] 85.7 [67.3–96] | 79.3 [60.3–92] 79.3 [60.3–92] 78.6 [59–91.7] | 2.6 [1.2–5.8] 3.3 [1.5–7] 4 [1.9–8.3] |
Author, year | Sample size, n | Threshold value | Timing | Timing outcome | TP | FP | FN | TN | Sensitivity % [95% CI] | Specificity % [95% CI] | LR + [95% CI] |
---|---|---|---|---|---|---|---|---|---|---|---|
5D EEG-derived indices | |||||||||||
5D.1 Bispectral Index (BIS) | |||||||||||
Park, 2018 [42] | 65 | ≥ 20.5 | 2.3 ± 1 h | 6 months | 14 | 3 | 2 | 46 | 87.5 [61.7–98.4] | 93.9 [83.1–98.7] | 14.3 [4.7–43.4] |
Seder, 2010 [46] | 83 | ≥ 24 | 280 (176–360) min | HD | 31 | 7 | 2 | 43 | 93.9 [79.8–99.3] | 86 [73.3–94.2] | 6.7 [3.4–13.4] |
Leary, 2010 [40] Leary, 2010 [40] Leary, 2010 [40] Leary, 2010 [40] Leary, 2010 [40] | 62 62 62 62 62 | > 30 > 40 > 45 > 50 > 60 | 24 h | HD HD HD HD HD | 19 16 13 11 4 | 25 13 6 5 3 | 1 4 7 9 16 | 17 29 36 37 39 | 95 [75.1–99.9] 80 [56.3–94.3] 65 [40.8–84.6] 55 [31.5–76.9] 20 [5.7–43.7] | 40.5 [25.6–56.7] 69 [52.9–82.4] 85.7 [71.5–94.6] 88.1 [74.4–96] 92.9 [80.5–98.5] | 1.6 [1.2–2.1] 2.6 [1.6–4.3] 4.6 [2–10.2] 4.6 [1.8–11.5] 2.8 [0.7–11.3] |
5D.2 Cerebral Recovery Index (CRI) | |||||||||||
Tjepkema-Cloostermans, 2013 [49] | 53 | > 0.57 | 18 h | 6 months | 17 | 0 | 9 | 27 | 65.4 [44.3–82.8] | 100 [89.5–100] | – |
Tjepkema-Cloostermans, 2013 [49] | 54 | > 0.69 | 24 h | 6 months | 7 | 0 | 20 | 27 | 25.9 [11.1–46.3] | 100 [89.5–100] | – |
Author, year | Sample size, n | Index | Threshold value | Timing | Timing outcome | TP | FP | FN | TN | Sensitivity % [95% CI] | Specificity % [95% CI] | LR + [95% CI] |
---|---|---|---|---|---|---|---|---|---|---|---|---|
6.1 Brain CT | ||||||||||||
Lee, 2017 [52] | 67 | GWRa | ≥ 1.25 | 124.5 ± 59.9 min | 1 months | 5 | 11 | 15 | 36 | 25 [8.7–49.1] | 76.6 [62–87.7] | 1.1 [0.4–2.7] |
Lee, 2017 [52] | 67 | QRAb | ≤ 5 | 1 months | 5 | 11 | 15 | 36 | 25 [8.7–49.1] | 76.6 [62–87.7] | 1.1 [0.4–2.7] | |
Lee, 2017 [52] | 67 | ASPECTS-bc | ≥ 15 | 1 months | 15 | 5 | 5 | 42 | 75 [50.9–91.3] | 89.4 [76.9–96.5] | 7 [3–16.7] |
Author, year | Sample size, n | Index | Timing | Timing outcome | TP | FP | FN | TN | Sensitivity % [95% CI] | Specificity % [95% CI] | LR + [95% CI] |
---|---|---|---|---|---|---|---|---|---|---|---|
6.2 Brain MRI: DWI and FLAIR | |||||||||||
Park, 2020 [54] | 36 | No cortical necrosis on DWI | 3.1 (2.4–4) h | 6 months | 21 | 6 | 0 | 9 | 100 [86.7–100] | 60 [32.3–83.7] | 2.4 [1.3–4.4] |
Oh, 2019 [56] Oh, 2019 [56] | 134 134 | No diffusion restriction in the cortex or deep grey matter No or single diffusion restriction in the cortex or deep grey matter | After RW | 6 months 6 months | 26 34 | 5 8 | 10 2 | 93 90 | 72.2 [54.8–85.8] 94.4 [81.3–99.3] | 94.9 [88.5–98.3] 91.8 [84.5–96.4] | 14.1 [5.9–34] 11.6 [5.9–22.6] |
Jang, 2019 [55] | 39 | No DWI lesions | 74.5 ± 16.1 h | 6 months | 11 | 2 | 1 | 25 | 91.7 [61.5–99.8] | 92.6 [75.7–99.1] | 12.4 [3.2–47.5] |
Park, 2020 [54] | 36 | No cortical necrosis on DWI | 77.6 (75.9–80) h | 6 months | 21 | 1 | 0 | 14 | 100 [86.7–100] | 93.3 [68.1–99.8] | 10.4 [2.3–47.9] |
Mlynash, 2010d [53] Mlynash, 2010d [53] Mlynash, 2010d [53] | 33 33 33 | No DWI or FLAIR lesions in the cortex No DWI or FLAIR lesions in the deep grey nuclei No DWI or FLAIR lesions in the cerebellum and pons | ≤ 8 days | 6 months 6 months 6 months | 14 9 18 | 3 2 12 | 4 9 0 | 12 13 3 | 77.8 [52.4–93.6] 50 [26–74] 100 [84.7–100] | 80 [51.9–95.7] 86.7 [59.5–98.3] 20 [4.3–48.1] | 3.9 [1.4–11] 3.8 [0.9–14.8] 1.2 [0.9–1.6] |
6.3 Brain MRI: GRE | |||||||||||
Jang, 2019 [55] | 39 | Summary GRE score = 0 | 74.5 ± 16.1 h | 6 months | 9 | 0 | 3 | 27 | 75 [42.8–94.5] | 100 [89.5–100] | – |