Table 1 Summary of findings regarding prognostic value of electroencephalographic reactivity in critically ill and postacute patients presenting with disorders of consciousness

Only nociceptive and/or tactile

Tsetsou et al. (2018) [81]

CA/H (TH)

EEG-R predicted good outcome

95 (75–99)

66 (49–80)

60 (42–76)

96 (79–99)

CPC at 3 months

Rossetti et al. (2017) [73]

CA/H (TH)

Reactive EEG predicted good outcome with accuracy = 86.6% (82.6–90.0)

80.4 (75.9–84.4)

CPC at 3 months

Topjian et al. (2016) [80]

CA/H (children)

Absence of reactivity was associated with worse EEG background category (p < 0.001), which is associated with death aOR = 3.63 (2.18–6.0) and unfavorable neurological outcome aOR = 4.38 (2.51–7.17).

PCPC at hospital discharge

Li et al. (2015) [66]

Mixed

EEG-R to thermal stimulation(warm water 42 ± 2 °C) was elicited in 11 patients, and 9 of them showed improved outcomes. Among the 10 patients with no EEG-R, 9 patients did not improve.

mGOS at 1 year

Lan et al. (2015) [64]

Mixed (children)

The poor-prognosis group had the lower proportion of events in reactive EEG patterns. Compared with patients with good prognosis, patients with poor prognosis had less frequent reactive EEG patterns as well as sleep architecture (p < 0.004).

Pediatric CPC

Kang et al. (2014) [61]

Mixed

Performance of the variable reactive EEG for recovery of awareness: OR = 21.648 (2.212 to 211.870).

66.7 (44.7–83.6)

75.0 (56.2–87.9)

66.7 (44.7–83.6)

75.0 (56.2–87.9)

GOS at 1 year follow-up

Visual only

Bagnato et al. (2017) [33]

Mixed

5 of the 16 patients with consciousness improvement showed EEG-R on baseline EEG (at admission), which was absent in all patients without improvement.

CRS-R at 6 months

Only patients with consciousness improvement showed the reappearance of EEG-R after 6 months. Nine of the 16 patients with consciousness improvement, corresponding to 81.9% of patients who did not show EEG-R at admission, had reappearance of EEG-R at the 6-month follow-up. On the contrary, none of the patients without consciousness improvement showed reappearance of EEG-R.

Nita et al. (2016) [38]

Mixed (children)

Intermittent photic stimulation induced reactivity of the burst-suppression pattern and standardized burst ratio reactivity appeared to reflect coma severity.

GCS

Bagnato et al. (2015) [50]

Mixed

Mean CRS-R scores were lower for patients without EEG-R than for patients with EEG-R, at admission (5.4 ± 3.1 versus 10.7 ± 4.3) and after 3 months (10.6 ± 7 versus 21.2 ± 3.5).

CRS-R at 3 months

Moreover, patients without EEG-R had less CRS-R score improvement after 3 months than patients with EEG-R (ANOVA, F_1,99 = 21.5; p < 0.001).

Auditory + nociceptive and/or tactile

Steinberg et al. (2018) [76]

Mixed

Reactive background EEG predicted survival aOR = 2.89 (1.49–5.59) and functionally favorable survival aOR = 1.51 (0.66–3.45).

CPC at hospital discharge

Duez et al. (2018) [55]

Mixed

Nonreactive EEG predicted poor outcome

40 (23–68)

100 (69–100).

CPC at 3 months

Johnsen et al. (2017) [37]

Neurosurgical

Nonreactive EEG predicted poor outcome

61 (42–77)

33 (06–76)

83 (62–95)

13 (2–42)

GOS at 3 months

Azabou et al. (2016) [8]

CA/H

Nonreactive EEG predicted an unfavorable outcome with AUC 0.82.

84

80

98

31

GOS at 1 year

Kang et al. (2015) [62]

Mixed

EEG-R predicted 1-month awakening from coma with AUC = 0.79 (0.71–0.88).

85.4 (71.6–93.5)

74.1 (60.7–84.4)

73.2 (59.5–83.8)

86.0 (72.6–93.7

CRS-R and CPC at 1 month

Sivaraju et al., (2015) [75]

CA/H (TH)

Nonreactive EEG was associated with poor outcome

79 (66–88)

86 (66–95)

92 (81–98)

65 (47–79)

GOS at discharge

Gilmore et al. (2015) [28]

Septic

Nonreactive EEG was associated with mortality

Mortality and mRS at 1 year

Ribeiro et al. (2015) [71]

CA/H

Reactivity of the first EEG might predict better survival in post-cardiac arrest patients with hypoxic encephalopathy and generalized or bilateral lateralized periodic epileptiform discharges on first EEG (p = 0.0794).

Survival at hospital

Su et al. (2013) [141]

CA/H (Stroke)

Dominant alpha wave without reactivity and dominant slow-wave rhythmic activity without reactivity were found to be correlated with poor outcome with ORs = 1.19 (0.27–5.14), and 1.82 (0.61–5.42), respectively.

mRS at 3 months

Howard et al. (2012) [59]

CA/H

EEG-R to external stimuli (p = 0.039) and the presence of spontaneous fluctuations in the EEG (p = 0.003) were significantly associated with a favorable outcome.

mGOS at hospital discharge

Zhang et al. (2011) [83]

CA/H (stroke)

Unfavorable EEG patterns, lack of EEG reactivity, pathologic N20 of SSEP, and pathological wave V of BAEP were associated with unfavorable outcome.

(92.4–97.0)

(82.5–99.5)

GOS at 6 months

Logi et al. (2011) [14]

Mixed

EEG-R is a good prognostic factor of recovery of consciousness in the postacute phase of brain injury; nevertheless, its absence is not invariably associated with a poor prognosis.

68.7

88.9

LCFS at 5 months

EEG reactivity predicted recovery of consciousness after 5 months from EEG recording with OR = 0.08 (0.01–0.44), p = 0.004 and 0.05 (0.01–0.53), p = 0.013, respectively, in univariable and multivariable logistic regression models.

Rossetti et al. (2010) [72]

CA/H

Unreactive EEG background was found in 3 of 45 (8%) survivors versus 53 of 65 (81%) nonsurvivors p = 0.001 (Fisher’s exact test). Unreactive EEG background was incompatible with good long-term neurological recovery (CPC 1–2) and was strongly associated with in-hospital mortality: aOR for death = 15.4 (3.3–71.9).

CPC at 3 and 6 months

Gütling et al. (1995) [58]

severe TBI

All but one patient with preserved EEG reactivity (96%) had a good global outcome, but 93% of the patients in whom EEG reactivity was absent had a bad outcome. Using discriminant analysis, EEG-R correctly classified 92% of the patients into good or bad global outcome groups. EEG-R is an excellent long-term global outcome predictor, superior to the central conduction time of the somatosensory evoked potentials and GCS.

GOS at 1,5 years

Auditory + nociceptive and/or tactile + visual

Li et al. (2018) [65]

CA/H

EEG-R predicted survival with OR = 8.75 (1.48–51.95), p = 0.017.

82.1

84.1

86.8

78.7

GOS at 6 months

Fernández-Torre et al. (2018) [57]

CA/H

In patients with a diagnosis of postanoxic alpha coma, theta coma, or alpha-theta coma, there was increased association of EEG-R with survival (p = 0.07).

CPC at 5 months

Fantaneanu et al. (2016) [56]

CA/H (TH)

EEG-R varies depending on the stimulus modality as well as the temperature. EEG to nipple pressure is the most sensitive EEG-R test for outcome during hypothermia, with a good specificity, and is associated with good outcomes during either hypothermic or normothermic periods.

75

79.5

CPC at hospital discharge

Braksick et al. (2016) [52]

Mixed

Absence of EEG-R was independently associated with in-hospital mortality:

In-hospital mortality

OR = 8.14 (4.20–15.79)

Mohammad et al. (2016) [68]

Septic (children)

A nonreactive background was noted in 48% (57 of 119) of patients on their first EEG and predicted abnormal outcome in children with encephalitis (OR = 3.8, p < 0.001).

LOS at last follow-up

Juan et al. (2015) [60]

CA/H

Seventy-two patients (37%) had a nonreactive EEG background during TH, with 13 (18%) evolving toward reactivity in NT. Compared with those remaining nonreactive (n = 59), they showed significantly better recovery of brainstem reflexes (p < 0.001), better motor responses (p < 0.001), transitory consciousness improvement (p = 0.008), and a tendency toward lower NSE (p = 0.067).

CPC at 3 months

Oddo and Rossetti (2014) [69]

CA/H (TH)

AUC for nonreactive hypothermic EEG for predicting mortality and poor outcome were 0.86 (0.81–0.92) and 0.81 (0.75–0.87), respectively

CPC at 3 months

Crepeau et al. (2013) [54]

CA/H

Nonreactive EEG was associated with poor outcome with OR = 17.05 (3.22–90.28).

CPC at hospital discharge

Sutter et al. (2013) [78]

Mixed

Nonreactive EEG background was independently associated with death in encephalopathic patients with triphasic waves: OR = 3.73 (1.08–12.80, p = 0.037).

Mortality and CPC at discharge

Bisschops et al. (2011) [51]

CA/H (TH)

EEG was unreactive in 15 of 23 patients (65.2%) with an unfavorable outcome and in none of the 4 patients with a good outcome (p = 0.015).

100 (75–100)

GOS at hospital discharge

Rossetti et al. (2010) [74]

CA/H (TH)

Nonreactive cEEG background during therapeutic hypothermia had false-positive rate of 0 (0–18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 [74%] of 19) had a favorable outcome.

100% (74 to 100%)

CPC at 2 months

Ramachandrannair et al. 2005 [70]

Mixed (children)

Among the 19 children with nonreactive EEG, 13 (65%) had unfavorable outcomes, including 10 deaths. Outcome was better in children with EEG-R (p = 0.023). EEG-R was associated with a lower PCOPCS score at follow-up (p = 0.002).

PCOPCS at 1 year

Amantini et al. (2005) [49]

Severe TBI

Awakening prediction with EEG-R: LR+ = 1.6 (0.8–3.2).

66.7

60.0

83.3

37.5

GOS at 1 year

Good outcome prediction with EEG-R: LR+ = 1.8 (1.2–2.9).

79.3

58.1

63.9

75.0

Young et al. (1999) [82]

Mixed

Nonreactive EEG was one of the individual factors strongly related to mortality: OR > 2.0.

> 0.80

EEG-R was among factors that favored survival rather than death.

Kaplan et al. (1999) [44]

Mixed

Presence of EEG reactivity in alpha coma correlated with survival (χ² = 5.231; p = 0.022). If the EEG showed no reactivity after cardiac arrest, patients were likely to die (χ² = 3.927; p = 0.0475).

GOS after hospital discharge

Not described

Søholm et al. (2014) [30]

CA/H

A favorable EEG pattern (including reactivity) was independently associated with reduced mortality with HR 0.43 (0.24–0.76), p = 0.004 (false-positive rate, 31%) and a nonfavorable EEG pattern (including no reactivity) was associated with higher mortality (HR = 1.62, 1.09–2.41, p = 0.02) after adjustment for known prognostic factors (false-positive rate, 9%).

30-day mortality and CPC at hospital discharge

Kessler et al. (2011) [63]

CA/H (TH) Children

During hypothermia, patients with EEGs in categories 2 (continuous but unreactive EEG) or 3 (discontinuity, burst suppression, or lack of cerebral activity) were far more likely to have poor outcome than those in category 1 (continuous and reactive EEG) (OR = 10.7, p = 0.023, and OR = 35, p = 0.004, respectively). Similarly, for EEG obtained during normothermia, patients with EEGs in categories 2 or 3 were far more likely to have poor outcomes than those in category 1 (OR = 27, p = 0.006, and OR = 18, p = 0.02, respectively).

PCPC at hospital discharge

Thenayan et al. (2010) [79]

CA/H

Of the 18 patients with nonreactive EEG, only 1 recovered awareness; of the 11 patients with EEG-R, 10 recovered awareness.

90 (57–100)

94 (70–100)

Awakening during hospitalization

Claassen et al. 7(2006) [53]

SAH

Outcome was poor in all patients with absent EEG reactivity

3-month mRS