By Aimee Aysenne, MD, MPH, and Chitra Venkatasubramanian, MBBS, MD, MSc
Neuroprognostication remains the elusive
and crucial component of neurocritical
care. Being able to rapidly and precisely
distinguish patients who have a chance at
meaningful neurological recovery from those
who do not, while avoiding the self-fulfilling
prophecy of early cessation of aggressive
support, remains one of the most difficult
duties of a neurointensivist. Here we present
three articles to aid in this task.
Neuron-specific enolase is a predictor of poor
outcome in cardiac arrest after TTM. Streitberger
KJ, Leithner CL, Wattenberg M, et al. Crit Care
Med 2017; 45:1145-1151.
The utility of neuron-specific enolase (NSE)
thresholds post cardiac arrest was evaluated
in this multicentered, retrospective study.
All patients were treated with TTM at 32-
34° for 24 hours. Treating physicians
knew NSE concentrations but were not the
sole deciding factor for prognostication.
Outcome was Cerebral Performance
Category (CPC) on discharge.
1,053 patients were included. At an NSE
threshold of >90 μg/L, PPV was 99% and
sensitivity was 48% to predict a poor outcome with CPC score of
4-5. There was no significant difference when including CPC 3
in the poor outcome group. Of the three patients who had good
outcome (CPC 1-2) despite NSE >90 μg/L, all had conditions that
could raise NSE levels outside of cardiac arrest. NPV for CPC 4-5
was 92% for NSE <17 μg/L, but NPV for severe HIE from CA is
This study suggests that markedly elevated NSE values (>90
μg/L) at three days post cardiac arrest in patients managed with
TTM strongly indicate a poor prognosis, and low values (<17
μg/L) indicate low likelihood of severe HIE incompatible with
reawakening. Other conditions that can raise NSE must be
excluded (malignant tumors, hemolysis, hematologic disease).
The NSE thresholds for poor outcome suggested in this study
are higher than in the TTM trial NSE subgroup analysis, which
showed poor outcome in all patients with NSE >50 μg/L. This
study suggests that NSE does have value in prognostication after
cardiac arrest, particularly when used in conjunction with other
Quantitative pupillometry predicts outcome after cardiac arrest.
Solari D, Rossetti A.O et al, Ann Neurol 2017; 81: 804-810.
In this single center, prospective observational study of adult
patients with coma after out of hospital cardiac arrest (OHCA),
the accuracy and predictive value of quantitative pupillary light
reactivity (PLR) based on pupillometry (automated infrared with
103 adult patients were enrolled. Pupil size, quantitative PLR and
constriction velocity at 24 and 48 hours were measured. TTM to
either 33°C (n=89) or 36°C was performed for 24 hours. Clinical
examination (motor response, pupil and corneal reflexes), video
EEG, SSEP, and peak NSE values were utilized. Decisions for
withdrawal of life support (WLST) were taken at 72 hours after
sedation and analgesia withdrawal. Outcome was assessed at one
year using CPC.
About half of the cohort died, mostly (94%) due to WLST from
severe brain damage. Non-survivors had a lower percent PLR and
lower constriction velocities. PLR of > 13% at 48 hours allowed
explicit separation between survivors and non-survivors. Further,
quantitative PLR < 13% at 48 hours had a 100% PPV for mortality,
with specificity of 100% and sensitivity of 61%. It performed
equally well compared to 48-hour non-reactive EEG background
and SSEP, but was much better than qualitative assessment of
pupillary reflex. The accuracy of the prognostic indicators did not
differ based on target temperature.
Using a blinded approach to minimize self-fulfilling prophecy,
this study shows that quantitative PLR of < 13% at 48 hours is
100% predictive of poor prognosis in a comatose patient after
cardiac arrest. This is similar prognostic performance of EEG
and SSEP and confirmation of superiority of quantitative PLR
to standard pupillary exam. If the findings of this study can be
validated, then simple bedside pupillometry with quantitative PLR
may help with neuroprognostication.
Sleep spindles after cardiac arrest may predict neurologic recovery in
pediatric patients. Ducharme-Crevie, L., Press, C.,Kurz, J., et al.
Pediatric Critical Care Medicine 2017; 18(5):452-460.
Sleep spindles on continuous electroencephalogram (cEEG)
can be a marker for neurologic recovery after cardiac arrest
(CA). Patients aged 6 months to 18 years who had cEEG cardiac
arrest were retrospectively identified via institutional database.
Standard of care included TTM to 35.5-36.0oC and cEEG.
Favorable neurological outcome was defined as Pediatric Cerebral
Performance Category (PCPC) score of 1 or 2 or no change from
baseline. Blinded reviewers classified sleep spindles on cEEG.
Spindles were classified as 1) absent, 2) abnormal (abnormal
or atypical morphology, frequency, asymmetry, and scalp
distribution), and 3) normal.
Forty patients were admitted with CA and underwent cEEG
monitoring. Median age was 6.1 years, 59% were male, and 68%
had in hospital arrest. Sleep spindles were observed in ten patients
with the first spindle observed at 12.2 hrs after ROSC. For those
with neuroimaging, there was no association with the presence
of cortical or thalamic injury and the absence of spindles. Sleep
spindles were present in 80% of patients with good neurologic
outcome and 8% of patients with a poor outcome. Of the patients
with poor outcomes, 10 of 24 had mild or moderately abnormal
EEG background with a similar association as with sleep spindles.
Appearance of sleep spindles within 24 hours after ROSC are
associated with a favorable neurologic outcome at six months
after CA in this study, similar to prognostication in stroke and
TBI. Further investigations are required for the consistent use of
sleep spindles as part of a prognostication algorithm in pediatric
patients after cardiac arrest.
Aimee Aysenne, MD
MBBS, MD, MSc