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Biomarkers and Neuroimaging of Brain Injury after Cardiac Arrest
Article in Seminars in Neurology · October 2006
DOI: 10.1055/s-2006-948322 · Source: PubMed
3 authors, including:
Prem Kandiah
Michel Torbey
Emory University
The Ohio State University
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Biomarkers and Neuroimaging of Brain Injury
after Cardiac Arrest
Prem Kandiah, M.D.,1 Santiago Ortega, M.D.,1
and Michel T. Torbey, M.D., M.P.H., F.A.H.A.1,2
Unfortunately, it remains a difficult task to predict with certainty which patients
will have a poor neurological outcome following cardiac arrest. Finding a quantitative
prognostic model of outcome has become the objective of many intensivists to assist
grieving families in making early difficult decisions regarding withdrawal of life support.
An ideal prognostic test should be readily available, easily reproducible, and associated with
a high degree of specificity for poor outcome. The goal is not to define which patients may
recover, but rather which patients have no likelihood of meaningful neurological recovery
at all to justify early withdrawal of support. The literature and the role of biochemical
markers in the blood and in the cerebrospinal fluid will be evaluated as prognosticators
following cardiac arrest. Radiological indicators of anoxic cerebral damage are reviewed.
Each serum or radiological marker has its pros and cons. To accurately prognosticate
following cardiac arrest, a multimodal scale or algorithm that incorporates serum markers,
radiological markers, and the neurological exam is clearly needed. As these techniques are
being evaluated more closely and as imaging modalities increase in sensitivity and
portability, physicians will continue to assist families by providing some guidance as to
which patients have no chance of meaningful recovery.
KEYWORDS: Neuron-specific enolase, S-100, cardiac arrest, radiological markers,
serum markers, prognostication
rior to the advent of modern cardiopulmonary
resuscitation (CPR), most patients who suffered a cardiac arrest died.1 Now, larger numbers of patients are
successfully resuscitated, but more than half die during
hospitalization, many from secondary brain injury.2,3
Many of those who do survive do not regain independent
function.4 Since the 1970s, several investigators have
attempted to better predict coma outcome using several
predictors, such as pupillary and oculocephalic reflexes
and variations in pain response. Several scoring systems,
including the Longstreth Awakening score and Glasgow
Coma Scale, have been developed.4–8 Unfortunately,
despite much study, it has remained difficult to predict
with certainty which patients will have a poor neurological outcome.
Finding a quantitative prognostic model of outcome has become the objective of many intensivists to
assist grieving families in making early difficult decisions regarding withdrawal of life support. An ideal
prognostic test should be readily available, easily reproducible, and associated with a high degree of
specificity for poor outcome. The goal is not to define
which patients may recover, but rather which patients
have no likelihood of meaningful neurological recovery
Department of Neurology and 2Department of Neurosurgery,
Medical College of Wisconsin, Milwaukee, Wisconsin.
Address for correspondence and reprint requests: Michel T.
Torbey, M.D., M.P.H., F.A.H.A., Director, Neurointensive Care
Unit, Medical College of Wisconsin, 9200 W. Wisconsin Avenue,
Milwaukee, WI 53226.
Hypoxic-Ischemic Encephalopathy; Guest Editor, Romergryko G.
Geocadin, M.D.
Semin Neurol 2006;26:413–421. Copyright # 2006 by Thieme
Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001,
USA. Tel: +1(212) 584-4662.
DOI 10.1055/s-2006-948322. ISSN 0271-8235.
This document was prepared for the exclusive use of Jeffrey Burns. Unauthorized distribution is strictly prohibited.
Table 1 Ranges of Cutoff Values Reported for
Neuron-Specific Enolase (NSE) and S-100
Time (h)
at all to justify early withdrawal of support. In this
review, we will present an assessment of serum and
radiological markers for neurological recovery following cardiac arrest.
The most convenient markers are those that can be
readily obtained at the bedside. Studies have measured
markers of brain injury in serum and cerebrospinal fluid
(CSF). There have been contradictory reports about the
development of elevated intracranial pressure (ICP)
following cardiac arrest,9,10 but none of these studies
reported herniation as a direct result of lumbar puncture.
Nonetheless, elevated ICP remains at least a theoretical
concern, and the search continues for prognostic peripheral markers in the bloodstream. Table 1 provides a list
of published biomarkers values.
Neuron-Specific Enolase
Neuron-specific enolase is a glycolytic enzyme found
mainly in neurons and neuroectodermal cells. High
serum levels have been reported with malignant tumors
such as neuroblastomas and small cell carcinoma of the
lung.11 Studies have shown that neuron-specific enolase
is a marker for severity of neuronal injury and clinical
outcomes in stroke,12 head injury,13 encephalitis,14 brain
metastasis,15 and status epilepticus.16
The prognostic role of neuron-specific enolase as
a biochemical marker of neuronal injury in cardiac
arrest was first investigated in the 1980s.17 Several
authors have since measured neuron-specific enolase
in serum17–25 or CSF17,26 to help prognosticate more
accurately neurological outcome following cardiac arrest.
Only two studies compared the performance of neuronspecific enolase in CSF and plasma.17,26 Roine et al17
measured neuron-specific enolase 24 hours following
cardiac arrest. Different cutoff levels of neuron-specific
enolase were used in CSF (> 24 ng/mL) compared with
serum (> 17 ng/mL). The specificity of neuron-specific
enolase was comparable between CSF and serum, but
sensitivity was lower in serum (40%) than CSF (74%). All
patients in the study with a CSF neuron-specific enolase
level > 24 ng/mL 24 hours after cardiac arrest remained
unconscious and died.17 These results contradicted the
findings of Martens et al26 who reported a higher
specificity for neuron-specific enolase when measured in
serum compared with CSF. Thus, it seems that at this
stage there is no clear-cut evidence that either serum or
CSF are any better. Measuring CSF neuron-specific
enolase is not very practical and may add a theoretical
risk of brain herniation from cerebral edema that may be
present following cardiac arrest. Hence, it appears to be
more practical and safer to measure serum neuron-specific enolase levels.
In an attempt to determine the optimum time
to measure neuron-specific enolase, different studies
have used different time parameters. Some used
24 hours,17,25,26 others 24 to 48 hour24,25,27 or 72
hours18–20,27 as their time frames. Fogel et al20 and
Schoerkhuber et al23 measured serial serum neuronspecific enolase for the subsequent 7 days following
cardiac arrest. Both studies reported improved prediction
when neuron-specific enolase levels were measured
within 48 to 72 hours following cardiac arrest. Neuronspecific enolase value at 72 hours after return of spontaneous circulation was the best predictor of neurological
outcome.28 Table 2 summarizes the performance of
neuron-specific enolase at different time frames.
S-100, a member of the Ca2þ-modulated proteins family, has both intracellular and extracellular regulatory
activities.29 It is expressed in varying abundance in
astrocytes, Schwann cells, adipocytes, melanocytes,
chondrocytes, skin Langerhans cells, lymphocyte subpopulations, skeletal muscle cells, and many neuronal
Table 2 Predictive Indices of Biomarkers in Serum and CSF
24 h
48 h
Specificity (%)
Sensitivity (%)
PPV (%)
NPV (%)
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populations.30 It modulates differentiation and proliferation of neurons and glia. S-100 effects are protective if
kept within cells at physiological levels. Animal models,
however, reveal that once secreted, large (micromolar)
concentrations can have a detrimental effect resulting in
apoptosis and neurodegeneration, and small (nanomolar) concentrations can be neuroprotective in nature.31
The first study, published by Rosen in 1998,22
demonstrated a significant correlation between S-100
serum levels, anoxia time, and degree of coma at day 1
and day 2. Comatose cardiac arrest patients with serum
S-100 levels persistently > 0.2 mg/L over 48 hours died
within 14 days of cardiac arrest.22 Martens21 obtained
similar results with a post hoc cutoff value of 0.7 mg/L at
24 and 48 hours following cardiac arrest. The cutoff
value of 0.7 mg/L has also been supported by HachimiIdrissi and colleagues32 with a good specificity, even
using S-100 admission levels. Table 2 summarizes the
performance of S-100 as a prognosticator of brain injury.
Long-term outcomes related to S-100 and neuron-specific enolase levels in cardiac arrest have also been
evaluated. Rosen et al27 found that high levels of serum
S-100 but not neuron-specific enolase predicted poor
outcome according to the Glasgow Outcome Scale
measured 1 year following cardiac arrest.
Comparison Between Neuron-Specific Enolase
and S-100
Very few studies actually compared neuron-specific enolase and S-100 head to head. Martens et al26 compared
serum S-100 and serum neuron-specific enolase at 24
hours, CSF S-100, and CSF neuron-specific enolase at
48 hours as predictors of coma following cardiac arrest.
The positive predictive value (PPV) and negative predictive value (NPV) for serum S-100 was 95 and 63%;
for neuron-specific enolase it was 86% and 65%, respectively. Cutoff levels was 0.7 mg/L for serum S-100 and
20 mg/L for neuron-specific enolase. This study found a
good correlation between serum and CSF S-100 and
neuron-specific enolase. Moreover, serum S-100 at
24 hours was noted to be as good as or superior to
CSF S-100 in predicting outcome.
Bottiger et al28 studied the predictive value of
sequential levels of S-100 and found that predictive value
was greatest at 24 hours. Results also revealed that the
odds ratio of having brain damage was 15 (95% confidence interval, 2.02 to 111.2) if S-100 level was
elevated within 2 hours after cardiac arrest.
In two independent randomized clinical trials, hypothermia for 12 or 24 hours resulted in improved neuro-
logical outcome in comatose survivors of out-ofhospital cardiac arrest.33,34 In 2003, Tiainen et al25
conducted a study assessing the role of neuron-specific
enolase and S-100 in patients after out-of-hospital
cardiac arrest requiring resuscitation under the conditions of hypothermia (33 18C). Blood samples for
neuron-specific enolase and S-100 were collected at
24, 36, and 48 hours after return of spontaneous
circulation. Neuron-specific enolase and S-100 levels
were lower in the hypothermia group compared with
the normothermia group. A decrease in neuron-specific
enolase value between 24 and 48 hours was observed in
30 of 34 patients (88%) in the hypothermia group and
16 of 32 patients (50%) in the normothermia group.
The decrease in neuron-specific enolase value was
associated with good outcome at 6 months. It was
also associated with regaining consciousness and survival for at least 6 months after return of spontaneous
circulation. A decrease in S-100 values was observed
between 24 and 48 hours in 17 of 34 patients (50%) in
the hypothermia group and in 15 of 33 patients (45%)
in the normothermia group. Decreased S-100 values,
however, had no relation to outcome. Tiainen et al25
concluded that hypothermia resulted in rapidly decreasing levels of serum neuron-specific enolase, reflecting
amelioration of secondary ischemic neuronal injury.
This is the first study to incorporate a therapeutic
intervention with serum markers. This is certainly
very important as it could open the door to test more
neuroprotective agents.
Several investigators reported a significant association
between elevated blood glucose following cardiac arrest
and poor neurological recovery.6,35–38 In 1997, Mullner
and colleagues39 evaluated the role of postischemic blood
glucose levels in patients with witnessed ventricular
fibrillatory arrest. They found that, in cardiac arrest
survivors, high blood glucose levels over the first 24 hours
after return of spontaneous circulation were independently associated with unfavorable functional neurological
recovery (146 39 mg/dL compared with 184 88 mg/dL).
Despite that, there does not appear to be support for
using glucose as a primary variable in predicting outcome following cardiac arrest. However, the admission
glucose and median glucose over the first 24 hours can
be used as an adjunctive measurement supporting the
gestalt of the individual patient’s prognosis.
Measurements of serum lactate levels on admission have
not been particularly accurate at predicting prognosis in
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postanoxic patients, requiring excessively high levels to
achieve 100% specificity for poor neurological outcome.39,40 Serial lactate measurements fared slightly
better, with levels higher than 2 mmol/L after 48 hours
correlating well with mortality or severe neurological
disability. Much like the use of glucose, both serum and
CSF levels of lactate can be used as supporting data, but
neither should be used as the primary method of prognostication in an individual patient.
Brain-Type Isoenzyme of Creatine Kinase
The brain-type isoenzyme of creatine kinase (CK-BB) is
primarily located in neurons and astrocytes, and as such
comprises 95% of the total creatine kinase activity of the
brain.41 Levels of CK-BB have been noted to be elevated
following global cerebral ischemic injury.42 There have
been several difficulties noted in the use of serum CKBB as a prognostic indicator. Many patients suffering
cardiac arrest will also develop myocardial infarctions
with resultant release of myocardial CK-MB isoenzyme
into the serum. Many of the available assays have some
cross-reactivity between the MB and BB isoenzymes,
making a serum test less accurate. In addition, the CKBB fraction peaks rapidly in the serum and is rapidly
inactivated with individual variation as to the speed of
Despite studies supporting the potential use of serological or electrophysiological markers in prognostication
following cardiac arrest, families and physicians continue
to require additional evidence prior to withdrawal of life
support. Hence, short of an autopsy, neuroimaging
provides a noninvasive reliable method to assess for a
structural brain injury.
Gray matter, in particular the hippocampus,
caudate-putamen, thalamus, large cell layers of the
neocortex, and Purkinje cells of the cerebellar cortex,
are selectively vulnerable to hypoxic injury. White
matter injury is believed to occur weeks to months
after global hypoxic injury. The imaging findings of
diffuse anoxia include diffuse cerebral edema, loss of
gray-white matter distinction, and selective neuronal
necrosis affecting the deep gray nuclei and of the
cortical layers III, IV, and V.44–47 Computerized tomography (CT) and conventional magnetic resonance
imaging (MRI) could play a role in prognostication
following diffuse cerebral anoxia.
Computerized Tomography
CT scan is one of the most frequently used ancillary tests
in comatose patients. A normal CT scan of the brain
shows a clear difference between white matter with its
high lipid content and gray matter with its high water
content.48 After cardiac arrest, the inadequate production
of adenosine triphosphate that accompanies global ischemia results in an overall increase in water content (cytotoxic edema).49,50 Furthermore, a delayed hyperemia after
resuscitation can lead to increased ICP and occasionally to
brain swelling.51 Initially, the cerebral blood vessels collapse so as to decrease intracranial volume and prevent
further increase in ICP. If systemic hypotension is corrected, this results in a distention of the deep medullary
veins.52–54 As a result, white matter becomes distended
with blood and appears denser on unenhanced CT scans.
Therefore, a loss of distinction between gray matter and
white matter after cardiac arrest could result from the
combination of a decreased gray matter intensity due to
cytotoxic edema and an increased white matter intensity
due to distention of the medullary draining veins.
It has been a general impression that a decreased
distinction between gray matter and white matter on CT
predicts poor outcome after cerebral insults. However,
qualitative assessment is not very reliable.55 Hence,
measuring the Hounsfield unit (HU) density may allow
a reliable quantifiable comparison between gray matter
and white matter. Torbey and colleagues56 compared
the HU density of gray matter of the caudate nucleus and
the HU of the white matter of the posterior limb of the
internal capsule. On noncontrast CT scans performed
within 48 hours of cardiac arrest, the gray matter/white
matter ratios were significantly lower than those of
control patients. Using a receiver operating characteristic
curve analysis, a gray matter/white matter ratio of < 1.18
was 100% predictive of death, whereas the survival rate
was 46% among patients with a gray matter/white
matter ratio of 1.18. Additional studies confirmed
that CT scan could be used as a reliable tool to evaluate
long term brain injury after cardiac arrest. Nunes et al57
have demonstrated that CT imaging revealed atrophy in
quantitative and qualitative analysis in patients between
1 and 3 years after cardiac arrest and this correlated with
impairment in cognitive testing. Table 3 summarizes the
findings in published studies that used CT as a prognosticator for cardiac arrest.
Magnetic Resonance Imaging
MRI during global cerebral hypoxia is possibly a valuable
tool for early prognosis of clinical outcome. Although
there is no doubt of the accuracy of MRI in identifying
early ischemic changes, the use of this technique is still
limited by several factors, such as the lack of availability
and expertise needed to interpret the images in several
centers and the long duration of the test, which may
expose critically ill patients with the potential for recurrent cardiac arrhythmias to undue risk.
In the hyperacute period (< 24 hours following cardiac arrest), Arbelaez and colleagues58 evaluated
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Table 3 Studies Using CT Scan for Prognosis in Cardiac Arrest Patients
Time to CT
Kjos et al74
24 h–5 d
Diffuse mass effect
90% died within 31 d
LD in GM LD in BG
LD in watershed areas
Fujioka et al75
24 h
No abnormal findings
2–6 d
Diffuse cerebral edema
62% died within 53 d
1 wk–2 mo
LD in caud, lenticular
48 h
Diffuse cerebral atrophy
LD in caud and put
100% died
ID in posterior limb of IC
HU ratio < 1.18
nuclei and thalamus
Torbey et al56
LD, low density; ID, increased density; GM, gray matter; BG, basal ganglia; caud, caudate; put, putamen; IC, internal capsule; HU, Hounsfield
diffusion-weighted imaging (DWI) findings in 10 patients with global cerebral anoxia. Using both low-b
value (B ¼ 30 s/mm2) and high-b value (B ¼ 1100 s/mm2)
diffusion imaging, investigators were able to find abnormal signal in the cerebellum, basal ganglia, and cortex
in under 24 hours. All of the patients demonstrating
DWI changes had a poor neurological outcome (death
or vegetative state). Interestingly, conventional T1- and
T2-weighted imaging were normal.
In the acute-subacute period (24 hours to
20 days), abnormalities on MRI could now be seen on
T1- and T2-weighted images.58–61 During this period
there is a reperfusion of the ischemic regions, but this
may not be sufficient to restore normal cellular homeostasis and cytotoxic edema may result. In addition, the
phenomenon of ‘‘late neuronal death,’’62 which predominantly affects the neocortex, hippocampus, and basal
ganglia, also may contribute to the abnormalities present
on conventional T2-weighted and DWI.
Els et al61 evaluated both DWI and apparent
diffusion coefficient (ADC) changes following global
hypoxia and found that an increase of signal intensity
on DWI is associated with an ADC decrease to 60 to
70% of control in large areas of the parietal, temporal,
and occipital cortex correlates with irreversible tissue
injury. However, in contrast with DWI, this decrease
was not observed in the cerebellum and thalamus.
Several studies have also demonstrated that ADC
declines as a function of time following global cerebral
In the late subacute period (14 to 20 days), DWI
shows a diffusely bright white matter, a finding that was
not that obvious on conventional MRI. Several mechanisms may explain these findings, including increased
pH secondary to lactic acid, release of protons that
contribute to glial cell damage,60,65 and glutamate effect
on glial cells receptors.66
In the chronic period (21 to 22 days), DWI
images may be normal. Laminar necrosis can now seen
on conventional MRI. During this period cellular death
and axonal destruction occur, which may lead to an
increase in extracellular space and greater freedom for
Brownian motion.67
Although earlier studies focused primarily on
gray matter injury following cerebral ischemia, DWI
opened the door for evaluating white matter injury as
well. The results of these studies were contradictory to
the common belief that white matter injury usually
occurs later in the course following cardiac arrest.
Chalela et al59 presented a case series in which MRI
with T2-weighted imaging and DWI was obtained on
seven comatose patients between 1 and 6 days following
severe anoxic injury. Only two of the seven patients had
primary cardiac arrest; the rest had a multitude of
causes including cocaine overdose, carbon monoxide
intoxication, hypoxemic respiratory failure, and septic
shock. Restricted DWI lesions were prominent
throughout the white matter in the periventricular
region, corpus callosum, and internal capsule. These
findings were corroborated with decreased ADC mapping. Similarly, Arbelaez and colleagues58 evaluated
DWI findings in 10 patients with global cerebral
anoxia. Investigators were able to find white matter
changes in the subacute period of 14 to 20 days
following injury. These studies demonstrated that myelinopathy can occur quite early following anoxic injury
and holds potential for evaluation as a prognostic
indicator. The fact that this leukencephalopathy occurred earlier than would be expected for a Wallerian
degeneration suggests that it may be a result of the
primary insult caused by diffuse cerebral anoxia, impaired cerebral perfusion, or both.58 As a result, an early
axonal and oligodendrocity injury is produced independently of neuronal injury.68
Some studies have hypothesized that DWI could
be used to determine the cause of the global hypoxic
damage as different types of anoxic brain injury can lead
to different imaging features. DWI hyperintensity
throughout the cerebral cortex suggests devastating,
diffuse hypoxic ischemia typically seen after cardiac
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Table 4 Review of MRI Studies
(< 24 h)
(24 h–13 d)
Late Subacute
(14–20 d)
(> 21 d)
Arbelaez et al58
Chalela et al59
Wijdicks et al60
Els et al61
arrest, whereas a pattern of DWI hyperintensity
restricted to the thalamus and selected cortical regions
suggests primary hypoxic injury.46,69 Nevertheless, in all
these studies the main areas affected in early anoxia were
gray matter areas.
Therefore, it can be concluded that MRI and
DWI/ADC imaging may be a useful tool to assess
prognosis in comatose patients after cardiac arrest.
Table 4 summarizes the findings of four studies using
MRI as a marker of brain injury. Hence, further
randomized controlled trials, with higher sample of
patients, are needed to evaluate the significance of
different radiological patterns and their relationship to
clinical prognosis and survival.
Positron Emission Tomography Scan
Very few authors have investigated the prognostic role
of positron emission tomography during the early
period after cardiopulmonary resuscitation. Edgren et
al40 reported a noticeable decrease in blood flow and
oxygen metabolism in comatose patients 1 day after
CPR. Interestingly, an increase in the oxygen extraction ratio was also found. Furthermore, comatose
patients showed a progressive decline in oxygen metabolism that was more remarkable in the putamen and
occipital cortex in comparison with patients who woke
To avoid false pessimistic prognostication, the cutoff
values in most studies for both S-100 and neuronspecific enolase are designed to produce (100%) specificity for poor outcome. Unfortunately, by using this
method, the sensitivity of these biomarkers is signifi-
cantly lowered. Some studies have tried to bridge this
problem by using a multimodal approach to collectively
improve prognostication after cardiac arrest.
Zingler and colleagues70 prospectively investigated the predictive power of serum concentrations of
neuron-specific enolase and S-100 as well as somatosensory-evoked potentials (SEPs) after cardiac arrest. By
combining both S-100 and neuron-specific enolase (at
100% specificity), the sensitivities could be markedly
increased on day 1 (from 52.9 to 58.8%), day 3 (from
75.9 to 87.5%), and day 7 (from 57.1 to 71.4%). The best
predictor of negative outcome was neuron-specific enolase alone at cutoff point 43 mg/L on day 2. This value
resulted in a sensitivity of 91% and a specificity of 100%.
SEPs showing bilateral loss of cortical responses identified patients who did not regain consciousness with a
specificity of 100%.70
Meynaar et al24 found an improved predictability
of poor neurological outcome when they combined
neuron-specific enolase, Glascow Coma Scale, and
SEP. The sensitivity increased from 64 to 76% with a
specificity of 100%.24 These findings were in contradiction to the finding of Bassetti et al.71 Bassetti’s group
found that both neuron-specific enolase and ionized
calcium did not provide any additional prognostic assistance to repeated clinical exam (including Glascow
Coma Scale), electroencephalogram, and median nerve
SEP. It is important to keep in mind that neuronspecific enolase levels and ionized calcium levels were
only measured in 16 patients out of 60.
Similarly, Pfeifer and colleagues72 demonstrated
that the combination of three variables—(1) Glasgow
Coma Scale < 6; (2) serum neuron-specific enolase
65 ng/mL; and (3) serum S-100 1.5 mg/L—at
72 hours after return of spontaneous circulation improved the pre- diction of outcome in postarrest coma.
Unconsciousness for > 48 hour and Glascow Coma
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Table 5 BrANOS Scale
Table 6 Summary of Poor Prognostic Indicators
Admission GCS < 8
Serial neuron-specific enolase levels on days 0–3 > 35 ng/mL
Serial S-100 levels on days 0–3 > 0.2 ng/mL
> 15
Head CT at 24–48 h GM/WM ratio < 1.18
MRI at 72 hours
Restricted diffusion in the cerebral and cerebellar cortices,
caudate nuclei, putamen, globus pallidi, and/or thalami
GCS, Glasgow Coma Scale; GM, gray matter; WM, white matter.
Duration of arrest (min)
BrANOS score 10
Best reverse GCS
(15-GCS) in 24 h
Hounsfield unit ratio
< 1.18
GCS, Glasgow Coma Scale.
Scale < 6 predicted a 61-fold and a 11-fold risk of poor
neurological outcome, respectively, 72 hours post–cardiac arrest. Serum neuron-specific enolase levels 65
ng/mL and S-100 levels 1.5 mg/L increased the risk of
death and persistent vegetative state by 17- and 13-fold,
respectively. Combining the Glascow Coma Scale with
elevated serum concentrations of both neuroproteins
above the cutoff levels resulted in an improved prediction
of poor neurological outcome with a specificity of
The Brain Arrest Neurologic Outcome Scale
(BrANOS) was developed as a way of encompassing
both clinical and radiological markers of brain injury into
a predictive model in the setting of global anoxic injury
following cardiac arrest.73 The scoring system is outlined
in Table 5. In 32 patients with witnessed cardiac arrest,
survivors had a significantly lower BrANOS score (8 2
points) compared with nonsurvivors (13 1 points).
The scale predicted death within 2 weeks with 100%
PPV and 100% specificity for a score 14. Using a
perhaps more realistic measurement of outcome, the
scale also predicted the combined outcome of death
and severe disability (Glasgow Outcome Score ¼ 3)
with 100% PPV and specificity for a score 10. This
scale provides another method to quantitatively predict
outcome, although it will need to be prospectively
validated prior to general application.
The current serum or radiological markers have their
pros and cons. To accurately prognosticate following
cardiac arrest, a multimodal scale or algorithm that
incorporates multiple parameters; specifically serum
markers, radiological markers, and the neurological
exam, is clearly needed. Table 6 summarizes the serum
and radiological prognosticators of poor neurological
outcome following cardiac arrest. As these techniques
are being evaluated more closely and as imaging modalities increase in sensitivity and portability, physicians
will continue to assist families by providing some guid-
ance as to which patients have no chance of meaningful
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