2021 - Brain Death - Death by Neurologic Criteria Determination

Neurologic Outcome REVIEW ARTICLE

Prediction in the C O N T I N U UM A U D I O
I NT E R V I E W A V A I L AB L E
ONLINE
Intensive Care Unit 

VIDEO CONTENT
By Carolina B. Maciel, MD, MSCR A V AI L A B L E O N L I N E
ABSTRACT
PURPOSE OF REVIEW: The burden of severe and disabling neurologic injury
on survivors, families, and society can be profound. Neurologic outcome
prediction, or neuroprognostication, is a complex undertaking with
many important ramifications. It allows patients with good prognoses
to be supported aggressively, survive, and recover; conversely, it
avoids inappropriate prolonged and costly care in those with devastating
injuries.
RECENT FINDINGS:Striving to maintain a high prediction performance during

prognostic assessments encompasses acknowledging the shortcomings of
this task and the challenges created by advances in medicine, which
constantly shift the natural history of neurologic conditions. Embracing the
unknowns of outcome prediction and the boundaries of knowledge
surrounding neurologic recovery and plasticity is a necessary step toward
refining neuroprognostication practices and improving the accuracy of
prognostic impressions. The pillars of modern neuroprognostication
include comprehensive characterization of neurologic injury burden
(primary and secondary injuries), gauging cerebral resilience and estimated
CITE AS:
neurologic reserve, and tying it all together with individual values
CONTINUUM (MINNEAP MINN)
surrounding the acceptable extent of disability and the difficulties of an 2021;27(5, NEUROCRITICAL CARE):
arduous convalescence journey. 1405–1429.
Address correspondence to
SUMMARY: Comprehensive multimodal frameworks of neuroprognostication Dr Carolina Maciel, McKnight
using different prognostic tools to portray the burden of neurologic injury Brain Institute, 1149 Newell Dr,
coupled with the characterization of individual values and the degree of L3-100, Gainesville, FL 32610,
carolina.maciel@neurology.ufl.
cerebral reserve and resilience are the cornerstone of modern outcome edu.
prediction.
RELATIONSHIP DISCLOSURE:
Dr Maciel serves on the editorial
boards of Critical Care
Explorations, eNeurologicalSci,
INTRODUCTION
and Neurocritical Care ON CALL.
N
eurologic outcome prediction is perhaps the most traditional
undertaking neurologists have been tasked with, besides lesion UNLABELED USE OF
PRODUCTS/INVESTIGATIONAL
localization. It is also arguably the most difficult one, as accurate USE DISCLOSURE:
outcome prediction is an art that is fluid. Inherently a moving Dr Maciel reports no disclosure.
target, neuroprognostication should shift constantly with the
advent of new diagnostic and therapeutic tools, which, in turn, change the © 2021 American Academy
natural history of disease processes and humble even seasoned neurologists. of Neurology.
CONTINUUMJOURNAL.COM 1405
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

NEUROLOGIC OUTCOME PREDICTION
Surviving a severe acute illness to intensive care unit admission is the

beginning of an arduous journey, during which efforts to sustain life with
aggressive organ support are often the main priority. Not uncommonly, comfort
and dignity are sacrificed to some extent during the daily battle against death. On
a day-to-day basis (or multiple times per day in unstable patients) critical care
providers and families ponder the benefit of aggressive interventions and life
support against their tolls; neuroprognostic impressions are within the core of
this reasoning, and guide end-of-life decision making. Deciding whether or not to
continue aggressive treatment relies on the assessment of the severity of
neurologic injury, the potential for neurologic recovery, and how the expected
deficits fit within individual perspectives of a tolerable level of disability.
IMPACT OF NEUROPROGNOSTICATION
The impact of outcome predictions in the clinical course of devastating brain
injuries cannot be overstated. The burden of disabling neurologic injury on
survivors, families, and society can be profound. Accurate neuroprognostication
allows patients with good prognoses to be supported aggressively, survive, and
recover; conversely, it avoids inappropriate prolonged care that may not be
aligned with the goals of care in those with devastating injuries.
Neuroprognostication also guides termination of efforts in cardiac arrest and
resuscitation and helps provide closure for families.
However, the positive impact of outcome prediction hinges upon its accuracy.
Inappropriately pessimistic prognostic impressions may claim the lives of one in
four cardiac arrest survivors, of whom one in six might have survived to an
ambulatory state by hospital discharge if given a chance to recover.1 On the other
end of this spectrum, delivering maximal therapy targeting survival to patients
with devastating spontaneous intracranial hemorrhages may prevent in-hospital
deaths in 65% of cases, although enduring such a journey may be regarded as a
torment if nearly all survivors would ultimately die in the subsequent 12 months
or be rendered severely disabled.2 This is so important that multiple societies
have put forth position statements defining futile and potentially inappropriate
interventions for patients who are critically ill,3 providing guidance on how to
manage intractable treatment conflicts4 and centering on the outcome prediction
and psychosocial and ethical management of devastating brain injuries.5-7
THREATS TO ACCURATE NEUROPROGNOSTICATION

A multitude of factors may ultimately decrease the accuracy of final prognostic
impressions. Advances in diagnostic methods and neurotherapeutics may
challenge the prediction performance of previously studied prognostic tools, and
various cognitive biases may affect the interpretation of prognostic impressions.
Imprecision of Diagnostic Methods and Uncertainties in Clinical

Trajectories
Precision in detecting degrees of impairment in consciousness is contingent on
the diagnostic yield of evaluation methods, which are ever evolving.8 The
sensitivity of an examiner in detecting awareness of a patient’s response to motor
commands during a bedside neurologic evaluation fades in comparison to
advanced signal processing and analyses of ancillary tests, such as EEG and MRI.
More than one in seven patients who are unresponsive on examination may
display electrical responses reflecting activation of areas of the brain
1406 OCTOBER 2021

corresponding to spoken motor commands in the early phase following acute KEY POINTS
brain injury,9 a condition termed cognitive-motor dissociation (ie, a disconnection
● Neurologic outcome
between the activation of the region of the brain correlating to the task and the prediction, or
actual demonstration of the behavior). Recognizing this subset of patients is neuroprognostication, may
important, as their recovery trajectories may diverge significantly. Nearly half of directly impact outcomes,
unresponsive patients who exhibit signs of brain activation in the acute period health care costs, and
surrogates of patients via its
may attain at least partial independence at the 1-year mark, whereas only 14% of
mediation effect on
those who do not exhibit such signs of brain activation can achieve this goals-of-care decision
milestone.9 making.
The length of follow-up and timing of clinical and outcome evaluations also
play a pivotal role in the accuracy of neuroprognostic assessments. Early ● Devastating brain injuries
represent conditions that
evaluations may be heavily influenced by common confounders in the acute pose an immediate threat to
phase, such as the effect of sedating medications and of the postictal state life from a severe neurologic
following acute symptomatic seizures (CASE 10-1), and serial evaluations are insult in which limitation of
needed following a trial of neuroresuscitation (eg, CSF diversion and osmotic disease-targeted
interventions is being
therapy) (CASE 10-2). In addition, delayed assessments allow for a better considered in conjunction
evaluation of the overall effect of rehabilitation following acute neurologic with implementation of
injuries. For example, more than 80% of patients with moderate to severe comfort measures.
traumatic brain injury (TBI) who were unconscious upon hospital discharge
● Potentially inappropriate
recovered consciousness during rehabilitation in a 31-year sample of patients
treatments are different from
enrolled in the Traumatic Brain Injury Model System program; of these, 40% futile interventions. In the
achieved at least partial independence.10 Another example is the recovery former, a reasonable chance
trajectory following traumatic spinal cord injury (also dependent on length of exists of accomplishing an
effect sought by the patient,
follow-up), which led to the recommendation of 12-month follow-up
but the treatment team
assessments of patients with incomplete injuries (ie, American Spinal Injury may recognize competing
Association [ASIA] Impairment Scale grades B through D [TABLE 10-111-14]).15 ethical considerations that
Although the recovery in the initial 3 months following the spinal injury is warrant their withholding.
steepest, in a 2019 meta-regression analysis, studies with longer follow-up were The latter refers to the rare
event that the desired
associated with the highest conversion rate between injury grades, thus physiologic effect is not
representing neurologic improvement, except in patients with complete injuries attainable with the treatment.
(ie, ASIA grade A). Similar longitudinal improvement can be seen in many other
acute brain injuries, including hypoxic-ischemic brain injury, in which gains in ● It is essential to consider
each context when
function may occur beyond the first year.16 However, even individuals who interpreting clinical and
recover consciousness (defined as Glasgow Coma Scale scores ≥12) during index outcome evaluations in
hospitalization after cardiac arrest face high odds of unfavorable outcomes; more individual patients,
than one in three of those discharged ultimately die or experience at least particularly their timing in
relation to the injury,
moderate to severe disabilities in the subsequent 18 months.16
medications, and seizures
Furthermore, the impact of novel therapeutics (including surgical treatment) and the progress or lack
and their timing from the injury onset may vary considerably depending on thereof following
the disease process, particularly with reperfusion strategies in acute ischemic therapeutic and
rehabilitation trials.
stroke and decompressive surgeries in space-occupying lesions.
● Many factors modulate
Cognitive Biases the clinical course of severe
Increasingly recognized by the scientific community17 and patient advocacy neurologic injuries, yielding
groups, one of the main threats to accurate neuroprognostication is a type of heterogeneous longitudinal
trajectories; some patients
confirmation bias known as the self-fulfilling prophecy, in which the tool being may experience worsening
investigated in outcome prediction studies is also used in clinical decision of functional status after
making; the result is an inappropriately inflated prediction performance. This discharge, some will
exaggerated prediction performance mediated by the self-fulfilling prophecy improve, and some will
remain unchanged.
bias leads to a portentous vicious cycle in which the liberal use of tools and

extrapolation of evidence from flawed studies coupled with false security and
overly confident assessments compound in an untold toll of lives lost when it
does not need to be this way. Embracing the unknowns of outcome prediction
and the boundaries of knowledge surrounding neurologic recovery and its
plasticity is a commitment we neurologists ought to have to our patients and
colleagues, who rely so heavily on our prognostic impressions. Furthermore, this
vicious cycle blocks advancement of the field by contributing to knowledge gaps
shielded by dogmas in neurocritical care and exponentially impacts future steps
in research and clinical care.
CASE 10-1 A 23-year-old woman was brought to the emergency department after
being hit by a truck in a parking lot. She was intubated in the field and,
upon arrival to the emergency department, experienced a 90-second
generalized tonic-clonic seizure. The examination performed by the
neurosurgery resident was remarkable for 4/4 twitches on train-of-four
(suggesting no or minimal residual effect from neuromuscular blockade),
unreactive anisocoria (right eye 6 mm, left eye 4 mm), absent corneal
reflexes bilaterally, preserved cough and gag reflexes, and absent motor
responses to central and appendicular noxious stimuli. She was found to
have an acute right subdural hematoma with 11-mm right-to-left midline
shift and effacement of suprasellar cisterns (VIDEO 10-1); she was deemed
an unsuitable candidate for hematoma evacuation based on the poor
examination (owing to absent ocular reflexes and motor responses).
Upon admission to the neurocritical care unit, she was noted to have
spontaneous bilateral extensor posturing coupled with rigors and marked
tachycardia with hypertension, suggesting paroxysmal sympathetic
hyperactivity. Following a trial of osmotic therapy with 23.4% sodium
chloride, she started to localize bilaterally to noxious stimuli and
regained, albeit sluggish, pupillary reactivity to light. Prompt
communication with the neurosurgical team led to the decision to offer
decompressive craniectomy in an otherwise nonsurvivable injury even
with optimized medical management. She regained consciousness on
postoperative day 20 and was discharged to an acute rehabilitation
facility on postoperative day 47 after early cranioplasty for sunken flap
syndrome and CSF leak repair.
COMMENT This case illustrates the importance of placing the neurologic examination
findings into the context of potential confounders, particularly seizures
(eg, ongoing seizures, postictal state, and residual effect of
benzodiazepines) and the residual effect of drugs used in rapid-sequence
intubation, such as sedatives and neuromuscular blockade (which can be
evaluated at bedside with train-of-four or reversed with sugammadex, for
example). Furthermore, in acute brain injuries, it is imperative to consider
the examination findings following neuroresuscitation (eg, a trial of osmotic
therapy) when deciding on suitability for lifesaving interventions, as
therapeutic nihilism is associated with nearly 100% mortality.
1408 OCTOBER 2021

Therefore, this conventional approach to neuroprognostication (including
research) that ignores the effect of the self-fulfilling prophecy bias is no longer
acceptable. However, the alternative of avoiding or delaying definitive
prognostic impressions, or abolishing the possibility of withdrawing life support,
is not viable from humanistic and administrative standpoints. This renders the
self-fulfilling prophecy bias inherent to any neuroprognostic research, hence the
need for critically appraising the potential impact this bias may have imparted
when new evidence arises. The TRIPOD (transparent reporting of a
multivariable prediction model for individual prognosis or diagnosis) guidelines,
curated by the EQUATOR (Enhancing the QUAlity and Transparency Of health
Research) Network international initiative, provide great guidance on
transparent reporting of multivariable prediction models for individualized
prognosis18; however, these guidelines are not specific for neurologic outcome
prediction studies and fail to account for factors that reflect the influence of
self-fulfilling prophecy bias. Future scientific efforts must employ a standardized
and transparent approach in reporting data elements that allow readers to gauge
the impact of self-fulfilling prophecy bias in the prediction performance of the
neuroprognostic tools being investigated, for example, whether the institution
where the study was conducted used a standardized neuroprognostication
algorithm, and if so, whether the tool being investigated is part of routine
assessments or if the treatment team was blinded from the results of such testing.
Additionally, studies should report a breakdown of mortality: brain death, death
due to refractory cardiac arrest despite resuscitation attempts and aggressive
care, death due to withdrawal of life support because of perceived poor
A 94-year-old woman with hypertension presented to the emergency CASE 10-2

department with lethargy, projectile vomiting, and thunderclap
headache. She lost consciousness while being evaluated and was
intubated for airway protection without the need for sedatives or
neuromuscular blockade. Head CT demonstrated marked intraventricular
hemorrhage casting the entire ventricular system and leading to
hydrocephalus, as well as diffuse subarachnoid hemorrhage, on the
background of significant global atrophy (VIDEO 10-2). Following
ventriculostomy and gentle CSF drainage for 24 hours, she regained the
ability to localize central noxious stimuli and underwent coiling of an
anterior communicating artery aneurysm.
Her hospital course was complicated by dysphagia requiring
gastrostomy and dependence on CSF diversion requiring a
ventriculoperitoneal shunt. She was discharged to acute rehabilitation on
postbleed day 17 and returned home 8 weeks later, no longer relying on
artificial nutrition.
This case demonstrates another example of the important effect of COMMENT

neuroresuscitation techniques when deciding whether or not to offer
neurosurgical treatment. In this case, neuroresuscitation centered on
treating critical mass effect in midline structures and hydrocephalus.

neurologic prognosis, or death due to withdrawal of life support because of

medical condition. Reporting the timing of final neuroprognostic assessments
and withdrawal of life-sustaining therapies in relation to when the injury
occurred is important, as the evolution of the patient’s trajectory over time
is a key aspect in neuroprognostication for many reasons, from gauging
cerebral resilience and capacity for recovery to accounting for the potential
confounding effect of drugs and seizures and to evaluate for the burden of
TABLE 10-1 Commonly Used Disability Outcome Scales in Acute Neurologic Injuries
Scale/grade Description
American Spinal Injury Association Impairment Scale (AIS)11,a
A Complete. No sensory or motor function is preserved in the sacral segments S4-5.
B Sensory incomplete. Sensory but not motor function is preserved below the neurologic level and includes
the sacral segments S4-5 (light touch or pinprick at S4-5 or deep anal pressure) AND no motor function is
preserved more than three levels below the motor level on either side of the body.
C Motor incomplete. Motor function is preserved at the most caudal sacral segments for voluntary anal
contraction (VAC) OR the patient meets the criteria for sensory incomplete status (sensory function
preserved at the most caudal sacral segments S4-5 by light touch, pinprick, or deep anal pressure), and has
some sparing of motor function more than three levels below the ipsilateral motor level on either side of
the body. (This includes key or non-key muscle functions to determine motor incomplete status.) For AIS
grade C – less than half of key muscle functions below the single neurologic level of injury have a muscle
grade ≥3.
D Motor incomplete. Motor incomplete status as defined above, with at least half (half or more) of key
muscle functions below the single neurologic level of injury having a muscle grade ≥3.
E Normal. If sensation and motor function as tested with the International Standards for Neurological
Classification of Spinal Cord Injury are graded as normal in all segments, and the patient had prior deficits,
then the AIS grade is E. Someone without an initial spinal cord injury does not receive an AIS grade.
Modified Rankin Scale12,b
0 No symptoms at all.
1 No significant disability: despite symptoms, able to carry out all usual duties and activities.
2 Slight disability: unable to perform all previous activities but able to look after own affairs without
assistance.
3 Moderate disability: requiring some help but able to walk without assistance.
4 Moderately severe disability: unable to walk without assistance and unable to attend to own bodily needs
without assistance.
5 Severe disability: bedridden, incontinent, and requiring constant nursing care and attention.
6 Death.
CONTINUED ON PAGE 1411
1410 OCTOBER 2021

secondary injury. Many other important cognitive biases that pose a threat to
accurate neuroprognostication in severe brain injuries can be found in a
2017 editorial.19
Limitations of Outcome Assessments and Prognostic Models

The selection of meaningful outcomes in neuroprognostic studies involves an
important trade-off: balancing feasibility with the need for the delineation of
CONTINUED FROM PAGE 1410
Scale/grade Description
Glasgow Outcome Scale – Extended13,c
1 Death.
2 Vegetative state: condition of unawareness with only reflex responses but with periods of spontaneous
eye opening.
3 Low severe disability: patient fully dependent for all activities of daily living. Requires assistance to be
available constantly. Unable to be left alone at night.
4 Upper severe disability: can be left alone at home for up to eight hours but remains dependent. Unable to
use public transport or shop by themselves.
5 Lower moderate disability: able to return to work in sheltered workshop or noncompetitive job. Rarely
participates in social and leisure activities. Ongoing daily psychological problems (quick temper, anxiety,
mood swings, depression).
6 Upper moderate disability: able to return to work but at a reduced capacity. Participates in social and
leisure activities less than half as often. Weekly psychological problems.
7 Lower good recovery: return to work. Participates in social and leisure activities a little less and has
occasional psychological problems.
8 Upper good recovery: full recovery with no current problems relating to the injury.
Glasgow-Pittsburgh Cerebral Performance Category Scale14,d
1 Good cerebral performance: conscious, alert, able to work; might have mild neurologic or psychological
deficit.
2 Moderate cerebral disability: conscious, sufficient cerebral function for independent activities of daily life.
Able to work in sheltered environment.
3 Severe cerebral disability: conscious, dependent on others for daily support because of impaired brain
function. Ranges from ambulatory state to severe dementia or paralysis.
4 Coma or vegetative state: any degree of coma without the presence of all brain death criteria.
Unawareness, even if appears awake (vegetative state) without interaction with the environment; may have
spontaneous eye opening and sleep/awake cycles. Cerebral unresponsiveness.
5 Brain death: apnea, areflexia, EEG silence, etc.
EEG = electroencephalogram.
a
Note that this classification can be applied to injury at any level of the spinal cord; thus, the same grade may have markedly different levels of
disability depending on the level of injury.
b
Cutoffs commonly used for favorable outcome: 0 to 2 or 0 to 3.
c
Highly variable cutoffs for favorable outcome, usually 4 to 8, 5 to 8, or 6 to 8.
d
Cutoffs commonly used for favorable outcome: 1 to 2 or 1 to 3.

functional states, ideally with a granularity that allows for a projection of the
threat imparted to quality of life. The relevance of patient-oriented outcomes is
increasing, now trumping traditionally used end points that can be hard to
interpret in the context of severe brain injuries, such as mortality. For example,
a therapy that only increases survival without improving the degree of disability
is not as valuable as one that has a positive impact on disability-free survival.
Many validated functional outcome scales are used in clinical trials and
neuroprognostic studies, with ordinal scores lumped into favorable and
unfavorable categories (TABLE 10-1). Lack of understanding of the instrument
used to evaluate outcomes and the definitions used to dichotomize outcomes into
good or poor and failure to account for individual perspectives regarding the
acceptable level of disability compound as major threats to accurate
neuroprognostication.
NEUROPROGNOSTICATION FRAMEWORK
Neurologic outcome prediction is a longitudinal process that begins on the very
first encounter. Information pertaining to the burden of accrued neurologic
injury (both primary and secondary) should be assessed in the context of
individual factors pertaining to the potential for recovery and accepted level of
disability. The elements of this proposed neuroprognostication framework are
depicted in FIGURE 10-1. FIGURE 10-2,20-22 FIGURE 10-3,23-31 and FIGURE 10-432-38
summarize factors relevant to outcome prediction specific to hypoxic-ischemic
brain injury, TBI, and subarachnoid hemorrhage, respectively. Similar factors
also impact prognosis in acute ischemic stroke and intracerebral hemorrhage,
along with the overall volume and anatomic location of injured tissue. In
ischemic stroke, additional prognostic factors include details of reperfusion,
involved vessel and collateral status, and occurrence of hemorrhagic
transformation, among others.
Multimodal Characterization of Injury Burden Using Prognostic Tools

The most important characteristic
of a useful neuroprognostic tool is
to carry a virtually zero false-
positive rate when predicting a
poor outcome. This ensures a low
likelihood to contribute toward a
falsely pessimistic prognostic
impression that could, in turn,
lead to withdrawal of life-
sustaining therapies and deprive
individuals with potential for
recovery of a chance to regain
function. Additionally, the ideal
tool would carry a high sensitivity
to avoid missing individuals
destined to a poor outcome, FIGURE 10-1
which, in practical terms, could The neuroprognostication pyramid. Key
supporting elements of neuroprognostication
ultimately commit them to a include the perceived individual values and
potentially inappropriate estimates of burden of neurologic injury, cerebral
long-term journey depending on resilience, and reserve.
1412 OCTOBER 2021

KEY POINTS
● The neuroprognostication
literature has been blighted
by the self-fulfilling
prophecy bias, which
overinflates the prediction
performance of
neuroprognostic tools and
leads to overly confident,
and often inaccurate,
prognostic impressions.
● Modern
neuroprognostication
studies must attempt to
mitigate self-fulfilling
prophecy bias by reporting a
breakdown of deaths,
blinding the treatment team
to the studied tool
whenever possible, and
accounting for the timing of
prognostication in relation
to injury.
FIGURE 10-2
Summary of relevant factors when prognosticating hypoxic-ischemic brain injury. Several
demographic factors impact prognosis. Obesity and comorbidities can impact outcomes, but
this effect is heterogeneous across studies. Details of the injury mechanism and offered
therapies are very important. Better outcomes are generally seen in shockable versus
nonshockable rhythms, cardiac versus noncardiac etiology, in-hospital cardiac arrest versus
out-of-hospital cardiac arrest, witnessed versus unwitnessed events, and when bystander
cardiopulmonary resuscitation (CPR) is performed. Patients who have been offered prompt
coronary reperfusion therapies (if ischemic etiology) and targeted temperature management
(TTM) also have higher odds of achieving a favorable outcome. The presence of gasping during
arrest and relative bradycardia during TTM carry a favorable prognostic significance. The
thermoregulatory status also matters, as the occurrence of shivering during TTM and early
rebound hyperthermia reflect relative sparing of hypothalamic injuries; however, a higher
burden of hyperthermia is associated with secondary brain injuries. Additionally, exposure to
glycemic dysregulations, hypotension, and ventilatory derangements compound on other
factors that increase cerebral metabolism (eg, seizures) to exacerbate secondary injury.
Neuroprognostic tools should be used in combination and employed at optimal times to
mitigate the effect of confounders and maximize yield of prognostic impressions.20,21 Note
that no single factor has been consistently demonstrated to have 0% false-positive rates (FPR)
for predicting outcomes.22
↑ = increased; ADC = apparent diffusion coefficient; e-CPR = extracorporeal membrane oxygenation–
assisted cardiopulmonary resuscitation; NSE = neuron-specific enolase; ROSC = return of spontaneous
circulation; SSEP = somatosensory evoked potentials.

FIGURE 10-3
Summary of relevant factors when prognosticating traumatic neurologic injury. Several
demographic factors may impact outcome, but their prognostic impact has varied across
studies.23 Details of the injury mechanism and offered therapies are very important. In
penetrating injuries, outlining the areas of the nervous system that are affected, the caliber of
bullet, and whether retained fragments are present can be helpful. Every traumatic brain
injury harbors potential for associated systemic, neurovascular, and spinal injuries,24 which
also impact recovery trajectories. Even in isolated brain injuries, patterns of injury portend
different trajectories: patients with associated intraventricular hemorrhage and mass effect
are less likely to regain consciousness during rehabilitation.10 In spinal cord injuries, the
extent of neurologic recovery is lowest in thoracic and penetrating injuries and lowest in
American Spinal Injury Association (ASIA) Impairment Scale A and D grades.15 The occurrence
of hypotension and paroxysmal sympathetic hyperactivity, despite being treatable, carries a
negative impact on prognosis.25 Several prognostic biomarkers have been proposed in
traumatic brain injury.26 Coagulopathy has been associated with expansion of hemorrhagic
contusions in traumatic brain injuries; specific cutoffs vary across studies, and the displayed
values reflect the ones with a strong association with outcomes in the pooled analysis.27
Derived from peripheral white blood cell analysis, the neutrophil to lymphocyte ratio adds
prognostic information in traumatic neurologic injuries.28,29 Diffuse axonal injury is associated
with poor outcomes, but the strength of this association depends on grades of severity and
predominant location of injury; high burden of injury in specific areas in the brainstem30 and in
the corpus callosum appear to reflect the most severe end of this spectrum.31
↑ = elevated; INR = international normalized ratio.
1414 OCTOBER 2021

KEY POINTS
● Most helpful
neuroprognostic tools yield
objective information linking
injury burden with outcomes
with very low false-positive
rates.
● Bilaterally absent corneal

and pupillary light reflexes
carry significant prognostic
value with very low
false-positive rates when
predicting poor outcome
but are sensitive to the
effect of confounders.
FIGURE 10-4
Summary of relevant factors when prognosticating subarachnoid hemorrhage. Several
demographic factors and premorbid conditions are associated with outcomes.32 Higher
scores on radiologic and clinical scales are associated with poor outcome, but approximately
one-third of patients with poor-grade subarachnoid hemorrhage regain functional status.33,34
Endovascular treatment modalities are associated with better neuropsychiatric and
functional outcomes when compared to clipping.35 Many prognostic tools center on the
prediction of vasospasm and delayed cerebral ischemia because of their role in secondary
brain injury development.32 The most employed monitoring modality is transcranial Doppler;
however, its prediction performance varies widely because of technical factors and limited
temporal resolution. EEG has emerged as an attractive tool with high temporal and spatial
resolution; however, no consensus exists on thresholds for predicting delayed cerebral
ischemia and significant expertise is required for the interpretation of findings.36 Laboratory
abnormalities such as leukocytosis,37 hypokalemia, and hyponatremia are also predictors of
vasospasm.32 Important prevalent systemic complications that carry prognostic meaning for
poor outcome include paroxysmal sympathetic hyperactivity and stress-induced
cardiomyopathy.38
↓ = decreased.
the level of disability that is perceived as unacceptable. But no neuroprognostic

tool is infallible, and false-positive predictions of poor outcome have been
reported widely in neurocritical care. The use of multimodal approaches to
characterize injury burden is a promising tactic to circumvent the individual
shortcomings of prediction tools.39
The search for the holy grail of neuroprognostication has led to a growing
number of prediction models, scores, nomograms, and algorithms of varying
complexity, prediction performance, and applicability to specific disease states in
the neurocritically ill.40-43 Neuroprognostication practices vary widely, even for

patients who are comatose after cardiac arrest,44 for whom multiple guidelines
are available20,21 and recommended multimodal prognostic algorithms perform
relatively well.45,46 Scores grading the severity of injury can provide prognostic
information based on probabilities of death and disability and are most useful in
research for balancing groups and comparing cohorts. However, adopting
population-based scores to individual cases can be misleading and is
not recommended.
CLINICAL EXAMINATION. The clinical examination can provide critical prognostic

information, but it is the prognostic tool most susceptible to the effect of
confounders. Employing a meticulous technique when assessing brainstem
reflexes and motor responses is imperative to maximize the yield of findings. The
examination features most studied for their prognostic utility, particularly
following hypoxic-ischemic brain injury, include corneal and pupillary light
reflexes and motor responses to noxious stimulation.22 The evaluation of gag and
cough reflexes, particularly in patients who are intubated, can be helpful in
predicting the need for tracheostomy and gastrostomy; patients who tolerate the
endotracheal tube with minimal or no sedation likely will experience some
difficulty managing their own secretions upon extubation. Other components of
the clinical examination that carry prognostic significance are the occurrence of
paroxysmal sympathetic hyperactivity, or storming, in most acute brain injuries
and myoclonus after cardiac arrest. Paroxysmal sympathetic hyperactivity is
highly prevalent in the neurocritical care unit, affecting up to 10% of patients
with severe acute brain injuries, and is characterized by episodic and transient
paroxysms of dysautonomia with simultaneous increases in sympathetic and
motor activity. Usually triggered by any stimuli, the exaggerated response
includes marked elevation of blood pressure, tachycardia, tachypnea,
hyperthermia, sweating, rigors, and posturing (often extensor). The diagnosis
can be made using the Paroxysmal Sympathetic Hyperactivity Assessment
Measure.25 Recognizing this complication is important; patients with paroxysmal
sympathetic hyperactivity frequently require high doses of sedating medications
and prolonged hospitalizations and have worse morbidity and mortality.25
Postanoxic myoclonus, previously considered an agonal phenomenon, can have
distinct prognostic implications based on the timing of occurrence, clinical
manifestation at presentation, and associated EEG and MRI findings.22,47 In
traumatic spinal cord injuries, ASIA scores (TABLE 10-1) outlining the severity of
neurologic impairment below the level of injury carry major prognostic significance.
Neurologic improvement markedly differs across grades of spinal cord injury
severity; patients with ASIA grade C have the highest odds for the steepest
neurologic recovery, followed by patients with ASIA grade B, grade D, and, finally,
grade A. Although patients with ASIA grade D may achieve the best functional
status, their recovery trajectories tend to be less steep given lower burden of deficits,
illustrating a ceiling effect in the recovery from spinal cord injuries.15
NEUROPHYSIOLOGIC TESTS. Neurophysiologic tests yield diagnostic and prognostic

information, but their utility in the intensive care unit may be hindered by
limited availability and technical difficulties decreasing the signal to noise ratio in
this setting. EEG is the most widely used neurophysiologic prognostic tool in
critical care as it provides neuroprognostic information while patients are being
evaluated for nonconvulsive seizures and status epilepticus, which may also
1416 OCTOBER 2021

exacerbate brain injury burden. Many features of cerebral background activity
and of rhythmic and periodic patterns have prognostic utility, particularly in
hypoxic-ischemic brain injury.22 Of these, greater than 50% suppression of
background activity in the absence of sedation and loss of reactivity when a
standardized approach is used seem to be the most valuable features.20,21
The conjured electrophysiologic responses of the central and peripheral nervous
systems from applied sensory or motor stimuli (termed evoked potentials) carry
significant diagnostic and prognostic value in a myriad of neurologic conditions.
Bilateral absence of cortical peaks (N20 potentials, shown in FIGURE 10-5)
following stimulation of median nerves is helpful in predicting poor outcome in
hypoxic-ischemic brain injury, although the accuracy of this study hinges upon
technical factors and false-positive rates may reach 25%.22
Technical limitations also curb the potential for the widespread use of nerve
conduction studies and EMG in the evaluation of patients who are critically ill;
however, these tests can provide valuable prognostic information in autoimmune
neuromuscular disorders and in patients with suspected critical illness
neuropathy and myopathy (CASE 10-3).
NEUROIMAGING. Many scales exist to classify head CT findings and their

prognostic implications, such as the Marshall and Rotterdam CT scores in TBI
FIGURE 10-5
Schematic representation of median nerve somatosensory evoked potentials. Following
electrical stimulation of the median nerve, signals travel across the neuraxis, and the
generated potentials are captured by electrodes placed in the key positions to assess for
pathway integrity (lower left, magnified view). By convention, a peak reflects a negative
potential (N), and a nadir reflects a positive potential (P), which are followed by their
expected latencies in milliseconds: Erb point (N9), cervical cord (N13), thalamic ventral
posterolateral nucleus (VPL) (P18), primary sensory cortex (N20).

CASE 10-3 A 52-year-old woman with end-stage lung disease following severe acute
respiratory distress syndrome (ARDS) from severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) infection underwent evaluation
for lung transplantation. Her intensive care unit course was complicated
by severe refractory hypoxia, requiring prolonged neuromuscular
blockade, deep sedation, 4 weeks of venovenous extracorporeal
membrane oxygenation (ECMO), and prolonged dependence on artificial
life support requiring tracheostomy, gastrostomy, and renal replacement
therapy. She remained minimally responsive despite being off sedatives
for nearly a week, prompting a neurocritical care consultation for
neuroprognostication.
On examination, she opened her eyes to voice, tracked the examiner,
and followed simple axial commands with her eyes but was unable to lift
her head from the pillow. She had flaccid quadriplegia with absent deep
tendon reflexes and mute plantar reflexes, but grimacing was noted with
deep nailbed pressure. EEG demonstrated an organized alpha-theta
background with mild slowing of the posterior dominant rhythm at 8 Hz,
absent epileptiform findings, and preserved sleep architecture. Brain
MRI was unremarkable, and cervical spine MRI showed diffuse signal
abnormality in paraspinal muscles on short tau inversion recovery (STIR)
sequences, suggestive of postinfectious myositis. Nerve conduction
studies demonstrated diffusely reduced or absent sensory and motor
potentials, with preservation of conduction velocities and F waves when
potentials were identified; this suggested a severe sensorimotor axonal
polyneuropathy. Needle EMG revealed extensive insertional activity,
fibrillations and positive sharp waves, absent fasciculations, mildly
reduced amplitude and duration of motor unit action potentials, and
discrete recruitment in the upper extremity muscles with no voluntary
units in the lower extremity muscles; this was concerning for denervation
but can also be seen in myositis. CSF analysis was unremarkable, and
creatine kinase was less than 20 U/L.
COMMENT In this case, the degree of encephalopathy was initially perceived as a

barrier to offering lung transplantation and prompted a neurocritical care
consultation; however, in the absence of structural abnormalities on MRI
and in the setting of mild dysfunction on EEG, expected improvement is
likely. Far more concerning is the degree of neuromuscular weakness with
flaccid quadriplegia, profound axonal sensorimotor polyneuropathy, and
evidence of denervation with absent recruitment; this could represent a
significant barrier for liberation from mechanical ventilation even in the
setting of normal lungs. Nonetheless, abnormal STIR signal in muscle can be
seen in the setting of denervation and severe deconditioning, and in
noncontrast studies, this finding is nonspecific. This patient made strides in
her recovery journey; within the subsequent 2 weeks, she was able to be
weaned off renal replacement therapy and mechanical ventilation and no
longer needed lung transplantation.
1418 OCTOBER 2021

and modified Fisher Scale grade in subarachnoid hemorrhage. For more KEY POINT
information on the Marshall and Rotterdam CT classification scores, refer to the
● Neuroimaging is helpful in
article “Moderate and Severe Traumatic Brain Injury” by Christopher P. quantifying acute and
Robinson, DO, MS,48 in this issue of Continuum, and for more information on the chronic structural damage
modified Fisher Scale, refer to the article “Subarachnoid Hemorrhage” by Sherry and assisting in the
Hsiang-Yi Chou, MD, MSc, FNCS, FCCM,49 in this issue of Continuum. estimation of predicted
deficits and recovery
However, no single scale is universally accepted, and prospective head-to-head
trajectories.
comparison studies are lacking. MRI of the neuraxis is perhaps one of the most
useful tools in the evaluation of structural damage following severe neurologic
injuries. The risk associated with the required supine positioning of patients with
a flat head of bed and the decreased monitoring during imaging acquisition must
be carefully assessed, particularly for long studies. Another important caveat is
the variability in the quality of radiology reports in the real world as well as their
interpretation within the clinical context, often omitting key findings of
prognostic importance; this is why neurologists, who are best equipped to
perform clinical correlation according to patient-specific scenarios, must master
the interpretation of neuroimaging. Furthermore, most useful MRI methods
quantifying injury burden and the integrity of structural connectivity used in
prognostic studies, such as diffusion tensor imaging and quantitative
diffusion-weighted imaging analysis, are not widely available in clinical practice.
Nevertheless, MRI provides essential information on what regions of the brain
are affected, which is useful in outlining expected deficits and gauging the need
for long-term support (CASE 10-4). Additionally, MRI can provide key
information on factors that help estimate the individual’s cerebral reserve, such
as the burden of microvascular injury or white matter changes, degree of
atrophy, and areas of encephalomalacia. In TBI, diffuse axonal injury, which is
commonly diagnosed through susceptibility-weighted imaging (SWI) as
scattered microbleeds in the cerebrum and brainstem, has been traditionally
associated with unfavorable outcomes, although cumulative research has shown
that the relationship between diffuse axonal injury and outcomes is far from
linear. In a meta-analysis comprising 32 studies, 62% of patients with diffuse
axonal injury achieved favorable outcomes despite being 3 times more likely to
have poor outcome than patients without diffuse axonal injury.31 This
heterogeneity in the prognostic significance of diffuse axonal injury is owed, in
part, to different severity grades in the Adams Diffuse Axonal Injury Severity
Grade50; however, even the presence of grade 3 (the highest grade) does not
preclude a chance at regaining function. A 2021 MRI study scrutinized
neuroanatomic characteristics of diffuse axonal injury of patients with TBI who
were comatose at presentation but later regained consciousness.30 Subcortical
microbleed patterns were highly variable across the brainstem, thalami, and
hypothalamus, and despite consistent involvement of the so-called coma-causing
hot spot (ie, mesopontine tegmentum), patients were able to recover
consciousness, suggesting a relative resilience of arousal mechanisms.30 Refined
classifications accounting for age and involvement of the substantia nigra and
mesencephalic tegmentum have been proposed but have not been
widely adopted.51
CHEMICAL BIOMARKERS. The quest for the identification of biomarkers that carry
high prognostic significance in acute brain injuries has led to the recognition of
several promising candidates, and the list grows at a steady pace. However, many

CASE 10-4 A 53-year-old man was admitted to the burn intensive care unit following
an inhalational injury. His hospital course was complicated by failed
extubation, severe hypoxia, and cardiac arrest with pulseless electrical
activity; return of spontaneous circulation occurred after 27 minutes of
resuscitation efforts. He underwent targeted temperature management
to 33 °C (91.4 °F) and failed to regain consciousness upon discontinuation
of sedatives and rewarming.
On examination, he had absent corneal reflexes to saline squirt,
sluggish pupillary light reflexes, and absent motor responses to central
and appendicular deep noxious stimuli. His EEG evolution is shown in
FIGURE 10-6. Postanoxic status epilepticus resolved with benzodiazepine
and fosphenytoin. Noncontrast brain MRI obtained on day 4 post–cardiac
arrest showed minimal ischemic injury (VIDEO 10-3).
Somatosensory evoked potentials obtained on day 5 post–cardiac
arrest demonstrated attenuated but present N20 peaks. Given the
severity of his inhalation injury, he required high mechanical ventilation
support; however, renal and hepatic functions had normalized, and he
was liberated from vasopressor infusions. The prolonged need for
mechanical ventilation was anticipated, and his family asked about his
neurologic prognosis before considering early tracheostomy.
COMMENT This case illustrates the dilemma commonly faced by families and
providers in cases of indeterminate prognosis. Postanoxic status
epilepticus and absent corneal reflexes and motor responses point toward
a poor prognosis; however, resolution of status epilepticus with first- and
second-line therapies yielding to a nearly continuous and reactive
background and minimal injury burden on MRI are reassuring. Furthermore,
the residual effect of sedatives and likely lower sensitivity of the technique
employed to elicit corneal reflexes may have confounded the examination.
Here, the best approach is to center the discussion on the journey toward
recovery, which will include need for at least tracheostomy, continued
antiseizure medication, and possibly gastrostomy. The uncertainty
regarding the ultimate long-term neurologic outcome should be
acknowledged while maintaining cautious reassurance on the expected
high likelihood of longitudinal recovery given the patient’s young age and
preserved cerebral reserve.
1420 OCTOBER 2021

FIGURE 10-6
Evolution of EEG changes of the patient in CASE 10-4. All epochs represent 11-second,
60-Hz filtered recordings captured on longitudinal bipolar montage with high-pass filter at
1 Hz, low-pass filter at 70 Hz, and paper speed of 30 mm/s with sensitivity at 7 μV/mm. A,
Theta-delta background during hypothermia captured in the initial 12 hours following arrest.
B, Reactivity preserved with transient attenuation of theta frequencies (fourth second) and
increased delta power captured at 24 hours postarrest. C, Sharply contoured generalized
rhythmic delta activity at 2 Hz captured at 36 hours postarrest. D, Generalized periodic
discharges with associated rhythmicity averaging 25 discharges per 10 seconds meeting
criteria for electrographic status epilepticus captured at 48 hours postarrest. E, Reemergence
of theta background following 4 mg IV lorazepam reflecting therapeutic response.

limitations hinder their widespread use, including a lack of broad availability

outside research settings, inadequate turnaround times for being relevant in the
clinical realm, and intraassay and interassay variability that challenges the
interpretation of results and acceptance of universal cutoffs. The specificity of
serum biomarkers in predicting poor outcome can be jeopardized by the
occurrence of common confounders, such as hemolysis, which may be avoided
by using CSF instead of blood specimens. Balancing this improved specificity to
neuronal injury with the practical aspects of care for patients with severe injuries
can be quite challenging; obtaining a CSF sample in patients who are comatose
and do not have ventriculostomy can be difficult, particularly in those prone to
increased intracranial pressure. Many neuronal-specific biomarkers have been
studied in acute brain injuries, particularly in stroke,52 TBI,26 and
hypoxic-ischemic injuries in which serial measurements of neuron-specific
enolase,53 glial fibrillary acidic protein (GFAP),54 neurofilament light chain,26
and S100B26 may provide useful prognostic information.
Cerebral Reserve and Resilience

Although cerebral reserve and resilience are not adequately defined in the
literature and thus remain subjective concepts, they collectively convey the
notion of the brain’s ability to “bounce back” after injury. Despite some overlap,
they each express distinct nuanced information.
Cerebral reserve is akin to renal functional reserve, in which estimates
of the population of viable nephrons capable of increasing glomerular
filtration rates reflect the ability to be liberated from long-term renal
replacement therapy. Cerebral reserve encompasses more than just the cognitive
domain and reflects how much viable neural tissue is left. It is a concept that
helps us try to answer the question of whether the brain has the capacity to regain
a functional state.
Cerebral resilience reflects the brain’s ability to dodge an insult and can be
constructed by attempting to determine how well the brain has handled the
insult and how much more it can take. It is likely the reason some patients
recover from a prolonged cardiac arrest and others may experience a devastating
injury despite short and high-quality resuscitation.
Surrogate markers can be used to delineate cerebral reserve and resilience,
often based on neuroimaging. For example, a patient recovering
consciousness during the first week following a 60-minute refractory cardiac
arrest requiring mechanical support demonstrates high cerebral resilience
(particularly if with minimal ischemic injury burden on MRI). A stroke
survivor with advanced dementia and severe sepsis may present with coma
despite absence of acute structural injury on neuroimaging, reflecting a very
limited cerebral reserve.
Individual Values
Before conveying definitive prognostic impressions, clinicians should take a step
back and deconstruct the vague terms that are dichotomized in studies into
favorable/unfavorable outcomes. This necessary step will later allow for applying
the meaning of outcomes to an individual, which may be different than the
original connotation adopted by a study. Functional states with a moderate
degree of disability may be considered acceptable to some individuals even if
they fall into what a study considered poor outcome. The effort should center on
1422 OCTOBER 2021

employing a humanizing lens through which the patient’s personal values come KEY POINTS
into focus, thus answering the overarching question: “Who is this person?”
● The burden of white
Observing preinjury pictures and videos can be quite helpful during this process. matter disease and
Exploring past rehabilitation experiences can also be insightful. Asking the encephalomalacia and
following questions facilitates accruing this information; however, a true degree of atrophy
delineation of personal values can take time, often requiring multiple encounters compound on acute
structural damage,
with surrogates.
contributing substantially to
a poor cerebral reserve;
u What kind of routine activities does the patient find most pleasurable? estimates of cerebral
reserve help project
u When faced with a challenging task, does the patient tend to be more motivated or individualized expectations
withdrawn? How frustrated is the patient when significant assistance is required from of recovery trajectories.
others?
u What is the first word that comes to mind when describing the patient’s attitude toward ● The characterization of
life? individual values
surrounding the acceptable
extent of disability and of
the difficulties of an arduous
Communicating Final Prognostic Impressions convalescence journey is
Many surrogate-specific factors have an independent impact on decision making crucial in the process of
following goals-of-care discussions in severe acute brain injury, including neuroprognostication.
sociodemographic factors.55,56 Key differences exist between surrogates and
● When communicating
physicians in their preferences surrounding the communication of outcome prognostic impressions with
predictions. Surrogates welcome numeric estimates describing prognosis, thus surrogates, clinicians should
limiting the uncertainty that is perceived as frustrating, whereas physicians be compassionate but
assertive, focus on what is
refrain from this approach, fearing erroneous interpretation of probabilities by
known, avoid medical
surrogates.57 So how can one reconcile a surrogate’s preference for numeric jargon, and give concrete
estimates that may not necessarily apply to the patient in question with the need examples of expected
for admitting that uncertainties exist? Although this remains an important deficits and their potential
knowledge gap, as a start, physicians should honestly acknowledge uncertainties impact on daily activities.
as much as possible; failure to do so may be perceived as frustrating to families.58

Furthermore, it is helpful to be explicit when conveying what the expected deficits
are and how they may impact activities of daily living, while also contrasting the
patient’s preinjury status with both best and worst possible functional outcomes.
Destigmatizing common support measures may be necessary, as approximately
one-third of patients with severe acute brain injury who have received a
tracheostomy regain independence and nearly 80% are successfully decannulated
by 6 to 12 months.59 It is also important to discuss openly the anticipated hurdles
even in best-case scenarios, as such hurdles directly impact what may be
considered an acceptable journey for certain individuals. For example, regaining
consciousness and surviving a months-long intensive care unit journey with
super-refractory status epilepticus from limbic encephalitis may be considered a
miraculous recovery; however, disabling cognitive impairment coupled with the
compounded side effects of a complex antiseizure regimen may be considered
intolerable for many (CASE 10-5).
TRENDS
Exciting times lie ahead for the neurocritical care community. Building on the
remarkable progress in methods of detection, promotion, and prediction of
disorders of consciousness,60 the Curing Coma campaign,61 launched in 2019,
represents a concerted effort between the Neurocritical Care Society and the
National Institute of Neurological Disorders and Stroke. The task at hand is to fill

in key knowledge gaps, from developing novel therapies and identifying

endotypes of injury to refining neuroprognostication. Future efforts in
expanding follow-up times beyond the initial injury following acute neurologic
injury, including neurocognitive and neuropsychiatric assessments as well as
health-related quality of life, will be instrumental to further our understanding of
the natural history of disease states in the setting of modern medicine. Refining
methods of quantification of brain injury burden, including the validation of
objective thresholds associated with a high prediction performance and the use of
other modalities such as neurosonology and proteomics, will help expand our
prognostic arsenal. The use of artificial intelligence in the identification of
brain injury phenotypes is becoming a reality after promising pilot data in
hypoxic-ischemic brain injury.62 The field is also rapidly evolving in the area of
optimized communication between physicians and surrogates,63 and novel and
CASE 10-5 A 22-year-old previously healthy man was admitted with generalized
convulsive status epilepticus nearly 1 week after a viral illness. His clinical
course was complicated by super-refractory status epilepticus despite
ketamine 7.5 mg/kg/h, midazolam 2 mg/kg/h, propofol 50 mcg/kg/min,
pentobarbital 1.5 mg/kg/h, and six antiseizure medications at maximally
optimized doses. He had brainstem areflexia and absent motor responses
to central and appendicular noxious stimuli in the setting of therapeutic
coma. Workup was remarkable for nonenhancing T2 hyperintensities in
the limbic regions on brain MRI (VIDEO 10-4), moderate lymphocytic
pleocytosis with elevated protein on CSF analysis, and elevated serum
interleukins. No response to empiric plasma exchange, IV
immunoglobulin (IVIg), anakinra, and electroconvulsive therapy was seen.
He was started on rituximab when anti–glutamic acid decarboxylase
(GAD) antibodies were noted to be markedly elevated, and he tolerated
complete wean of anesthetics during the second week of hospitalization.
Recalcitrant seizures prevented down-titration of the antiseizure
regimen, and he remained deeply comatose. Prolonged need for life
support was anticipated, and his family asked about his neurologic
prognosis before considering tracheostomy and gastrostomy.
COMMENT In cases of new-onset refractory status epilepticus (NORSE), the

identification of seizure etiology is key when ascertaining neurologic
prognosis. When a clear cause is established, antiseizure therapies can be
tailored more effectively and estimations of predicted course are a bit less
challenging. Seizures from autoimmune etiologies can be monophasic
(such as often occurring in acute disseminated encephalomyelitis [ADEM]
or in anti–N-methyl-D-aspartate [NMDA] receptor encephalitis when a
provoking antigen is identified and removed) or remain refractory, leading
to highly debilitating drug-resistant epilepsy syndromes (such as
Rasmussen encephalitis and GAD encephalitis).
1424 OCTOBER 2021

feasible goals-of-care decision aid resources are currently being investigated with
promising results.64,65
PEDIATRIC CONSIDERATIONS
This general approach to neuroprognostication can be applied to the pediatric
population with a few caveats. Individual values may not be crystallized by the
time of injury, which creates difficulty in ascertaining acceptable levels of
disability. Additionally, one could argue that younger patients are more likely to
adapt to deficits and the magnitude of the effect from recalibration shifts
(ie, changing what is considered as an acceptable level of disability) may be much
higher. Younger patients have less atrophy and burden of white matter disease in
general, which renders their cerebral reserve and potential for neuroplasticity
higher than older adults. Developing brains are also notoriously resilient, and
dramatic recovery trajectories can be seen.
CONCLUSION
Neuroprognostication is a complex undertaking that not only impacts the
injured individual but also has broad ramifications relevant to public health
and society. Striving to maintain a high prediction performance during
prognostic assessments encompasses acknowledging the shortcomings of this
task and the challenges created by advances in medicine, which constantly shift
the natural history of neurologic conditions. The pillars of modern
neuroprognostication include a comprehensive characterization of injury
burden, estimation of cerebral resilience and reserve, and the patient’s
perception of acceptable degree of disability and attitude toward an arduous
convalescence journey.
ACKNOWLEDGMENT
The author thanks Megan Centrella for her skilled artwork contribution to this
article.
VIDEO LEGENDS
VIDEO 10-1 VIDEO 10-2
Admission head CT in a patient with severe Admission head CT in a patient with subarachnoid
traumatic brain injury. Video shows axial head CT hemorrhage. Video shows axial head CT, with the
demonstrating extensive skull base fractures with cursor demonstrating hyperdensities consistent
pneumocephalus (predominantly anterior to with acute blood completely filling the ventricular
pontomedullary junction and prepontine cistern), system, including the foramen of Luschka bilaterally
diffuse cerebral edema with effacement of (lateral apertures linking fourth ventricle to the
suprasellar cistern and loss of sulci diffusely, cerebellopontine cistern) and cerebral aqueduct.
compression of lateral ventricles, diffuse Subarachnoid hemorrhage fills the quadrigeminal
subarachnoid hemorrhage (most evident on the plate, and a predominance of blood is noted in the
right sylvian fissure), and acute right subdural interhemispheric fissure, suggestive of ruptured
hematoma with mass effect causing right-to-left anterior communicating artery aneurysm. Marked
midline shift. ventriculomegaly, particularly of temporal horns of
the lateral ventricle, and diffuse atrophy are also
© 2021 American Academy of Neurology. noted.
© 2021 American Academy of Neurology.

VIDEO 10-3 VIDEO 10-4

Brain MRI in a patient with postanoxic status Brain MRI in a patient with new-onset
epilepticus. Video shows (from left to right and top super-refractory status epilepticus. Video shows
to bottom) axial diffusion-weighted imaging (DWI), (from left to right and top to bottom) axial diffusion
apparent diffusion coefficient (ADC), weighted imaging (DWI), apparent diffusion
fluid-attenuated inversion recovery (FLAIR), and coefficient (ADC), fluid-attenuated inversion
susceptibility-weighted imaging MRI sequences. recovery (FLAIR), precontrast T1-weighted, and
Diffuse sulcal FLAIR hyperintensities are seen, postcontrast T1-weighted MRI sequences.
without corresponding restriction on DWI and ADC Multifocal restricted diffusion is seen,
sequences, which could reflect reversible changes predominantly in limbic structures (yellow arrows),
in the setting of hyperoxia or even a result of status including cortical insula, mesial frontal regions, and
epilepticus and no significant hypoxic-ischemic hippocampi as well as splenium (dashed orange
injury burden; the incidental small acute stroke in arrow). No corresponding changes are seen on the
the right corona radiata is not expected to lead to T1-weighted sequence (bottom left), and
significant disability. inadequate contrast administration suggested by
lack of physiologic uptake on postcontrast
© 2021 American Academy of Neurology. T1-weighted sequence (bottom middle) limits
evaluation for enhancement.
© 2021 American Academy of Neurology.
USEFUL WEBSITES
EQUATOR NETWORK BRAIN TRAUMA FOUNDATION
The Equator Network website provides a The Brain Trauma Foundation website provides a
compilation of guidelines for conducting and compilation of guidelines for the care of patients
reporting results in prognostic studies, including with traumatic brain injury.
checklists for quick reference.
braintrauma.org
equator-network.org/reporting-guidelines/tripod-
statement AMERICAN SPINAL INJURY ASSOCIATION (ASIA)
The American Spinal Injury Association website
CURING COMA provides a reference for administration of the ASIA
The Curing Coma campaign website provides scale.
resources for patients, families and caregivers,
asia-spinalinjury.org/international-standards-
researchers, and health care providers to promote
neurological-classification-sci-isncsci-worksheet
engagement in this important public health effort.
curingcoma.org/home
REFERENCES
1 Elmer J, Torres C, Aufderheide TP, et al. 5 Healey A, Leeies M, Hrymak C, et al. CAEP
Association of early withdrawal of life-sustaining Position Statement—management of devastating
therapy for perceived neurological prognosis brain injuries in the emergency department:
with mortality after cardiac arrest. Resuscitation enhancing neuroprognostication and maintaining
2016;102:127-135. doi:10.1016/j. the opportunity for organ and tissue donation.
resuscitation.2016.01.016 CJEM 2020;22(5):658-660. doi:10.1017/
cem.2020.357
2 Weimer JM, Nowacki AS, Frontera JA. Withdrawal
of life-sustaining therapy in patients with 6 Harvey D, Butler J, Groves J, et al. Management of
intracranial hemorrhage: self-fulfilling prophecy perceived devastating brain injury after hospital
or accurate prediction of outcome? Crit Care admission: a consensus statement from
Med 2016;44(6):1161-1172. doi:10.1097/ stakeholder professional organizations. Br J
CCM.0000000000001570 Anaesth 2018;120(1):138-145. doi:10.1016/j.
bja.2017.10.002
3 Kon AA, Shepard EK, Sederstrom NO, et al.
Defining futile and potentially inappropriate 7 Souter MJ, Blissitt PA, Blosser S, et al.
interventions: a policy statement from the Recommendations for the critical care
Society of Critical Care Medicine Ethics management of devastating brain injury:
Committee. Crit Care Med 2016;44(9):1769-1774. prognostication, psychosocial, and ethical
doi:10.1097/CCM.0000000000001965 management: a position statement for
healthcare professionals from the Neurocritical
4 Bosslet GT, Pope TM, Rubenfeld GD, et al. An
Care Society. Neurocrit Care 2015;23(1):4-13.
Official ATS/AACN/ACCP/ESICM/SCCM Policy
doi:10.1007/s12028-015-0137-6
Statement: responding to requests for
potentially inappropriate treatments in intensive
care units. Am J Respir Crit Care Med 2015;191(11):
1318-1330. doi:10.1164/rccm.201505-0924ST
1426 OCTOBER 2021

8 Giacino JT, Katz DI, Schiff ND, et al. 19 Rohaut B, Claassen J. Decision making in
Comprehensive systematic review update perceived devastating brain injury: a call to
summary: disorders of consciousness: report of explore the impact of cognitive biases. Br J
the Guideline Development, Dissemination, and Anaesth 2018;120(1):5-9. doi:10.1016/j.
Implementation Subcommittee of the American bja.2017.11.007
Academy of Neurology; the American Congress
20 Berg KM, Soar J, Andersen LW, et al. Adult
of Rehabilitation Medicine; and the National
Advanced Life Support: 2020 International
Institute on Disability, Independent Living, and
Consensus on Cardiopulmonary Resuscitation
Rehabilitation Research. Neurology 2018;91(10):
and Emergency Cardiovascular Care Science
461-470. doi:10.1212/WNL.0000000000005928
With Treatment Recommendations. Circulation
9 Claassen J, Doyle K, Matory A, et al. Detection of 2020;142(16_suppl_1):S92-S139. doi:10.1161/
brain activation in unresponsive patients with CIR.0000000000000893
acute brain injury. N Engl J Med 2019;380(26):
21 Nolan JP, Sandroni C, Böttiger BW, et al. European
2497-2505. doi:10.1056/NEJMoa1812757
Resuscitation Council and European Society of
10 Kowalski RG, Hammond FM, Weintraub AH, et al. Intensive Care Medicine guidelines 2021:
Recovery of consciousness and functional post-resuscitation care. Intensive Care Med
outcome in moderate and severe traumatic brain 2021;47(4):369-421. doi:10.1007/s00134-021-
injury. JAMA Neurol 2021;78(5):548-557. 06368-4
doi:10.1001/jamaneurol.2021.0084
22 Sandroni C, D'Arrigo S, Cacciola S, et al.
11 American Spinal Injury Association. International Prediction of poor neurological outcome in
standards for neurological classification of spinal comatose survivors of cardiac arrest: a
cord injury (ISNCSCI) worksheet. Accessed systematic review. Intensive Care Med 2020;
August 10, 2021. asia-spinalinjury.org/wp- 46(10):1803-1851. doi:10.1007/s00134-020-06198-w
content/uploads/2019/10/ASIA-ISCOS-
23 Mollayeva T, Mollayeva S, Colantonio A.
Worksheet_10.2019_PRINT-Page-1-2.pdf
Traumatic brain injury: sex, gender and
12 Banks JL, Marotta CA. Outcomes validity and intersecting vulnerabilities. Nat Rev Neurol 2018;
reliability of the modified Rankin scale: 14(12):711-722. doi:10.1038/s41582-018-0091-y
implications for stroke clinical trials: a literature
24 Mollayeva T, Sutton M, Escobar M, et al. The
review and synthesis. Stroke 2007;38(3):
impact of a comorbid spinal cord injury on
1091-1096. doi:10.1161/01.STR.0000258355.
cognitive outcomes of male and female patients
23810.c6
with traumatic brain injury. PM R 2021;13(7):
13 Wilson JT, Pettigrew LE, Teasdale GM. Structure 683-694. doi:10.1002/pmrj.12456
interviews for the Glasgow Outcome Scale and
25 Baguley IJ, Perkes IE, Fernandez-Ortega JF, et al.
the extended Glasgow Outcome Scale:
Paroxysmal sympathetic hyperactivity after
guidelines for their use. J Neurotrauma 1998;15(8):
acquired brain injury: consensus on conceptual
573-585. doi:10.1089/neu.1998.15.573
definition, nomenclature, and diagnostic criteria.
14 Cerebral Performance Categories Scale (CPC J Neurotrauma 2014;31(17):1515-1520. doi:10.1089/
Scale). Accessed July 9, 2021. ivr-ias.ch/wp- neu.2013.3301
content/uploads/2020/06/CPC_Scale.pdf
26 Thelin EP, Zeiler FA, Ercole A, et al. Serial
15 Khorasanizadeh M, Yousefifard M, Eskian M, sampling of serum protein biomarkers for
et al. Neurological recovery following traumatic monitoring human traumatic brain injury
spinal cord injury: a systematic review and dynamics: a systematic review. Front Neurol
meta-analysis. J Neurosurg Spine 2019:1-17. 2017;8:300. doi:10.3389/fneur.2017.00300
doi:10.3171/2018.10.SPINE18802
27 Yuan Q, Sun YR, Wu X, et al. Coagulopathy in
16 Peskine A, Cariou A, Hajage D, et al. Long-term traumatic brain injury and its correlation with
disabilities of survivors of out-of-hospital cardiac progressive hemorrhagic injury: a systematic
arrest: the Hanox study. Chest 2021;159(2): review and meta-analysis. J Neurotrauma 2016;
699-711. doi:10.1016/j.chest.2020.07.022 33(14):1279-1291. doi:10.1089/neu.2015.4205
17 Geocadin RG, Callaway CW, Fink EL, et al. 28 Zhao JL, Du ZY, Yuan Q, et al. Prognostic value of
Standards for studies of neurological neutrophil-to-lymphocyte ratio in predicting the
prognostication in comatose survivors of cardiac 6-month outcome of patients with traumatic
arrest: a scientific statement from the American brain injury: a retrospective study. World
Heart Association. Circulation 2019;140(9): Neurosurg 2019;S1878-8750(18)32930-9.
e517-e542. doi:10.1161/CIR.0000000000000702 doi:10.1016/j.wneu.2018.12.107
18 EQUATOR Network. Transparent reporting of a 29 Zhao JL, Lai ST, Du ZY, et al. Circulating
multivariable prediction model for individual neutrophil-to-lymphocyte ratio at admission
prognosis or diagnosis (TRIPOD): the TRIPOD predicts the long-term outcome in acute
statement. Updated October 1, 2020. Accessed traumatic cervical spinal cord injury patients.
August 10, 2021. equator-network.org/reporting- BMC Musculoskelet Disord 2020;21(1):548.
guidelines/tripod-statement/ doi:10.1186/s12891-020-03556-z

30 Bianciardi M, Izzy S, Rosen B, et al. Location of 41 Dijkland SA, Foks KA, Polinder S, et al. Prognosis
subcortical microbleeds and recovery of in moderate and severe traumatic brain injury: a
consciousness after severe traumatic brain systematic review of contemporary models and
injury. Neurology 2021;97(2):e113-e123. validation studies. J Neurotrauma 2020;37(1):1-13.
doi:10.1212/WNL.0000000000012192 doi:10.1089/neu.2019.6401
31 van Eijck MM, Schoonman GG, van der Naalt J, 42 Witsch J, Kuohn L, Hebert R, et al. Early
et al. Diffuse axonal injury after traumatic brain prognostication of 1-year outcome after
injury is a prognostic factor for functional subarachnoid hemorrhage: the FRESH score
outcome: a systematic review and meta- validation. J Stroke Cerebrovasc Dis 2019;28(10):
analysis. Brain Inj 2018;32(4):395-402. 104280. doi:10.1016/j.
doi:10.1080/02699052.2018.1429018 jstrokecerebrovasdis.2019.06.038
32 Rumalla K, Lin M, Ding L, et al. Risk factors for 43 Sutter R, Semmlack S, Opić P, et al. Untangling
cerebral vasospasm in aneurysmal subarachnoid operational failures of the Status Epilepticus
hemorrhage: a population-based study of 8346 Severity Score (STESS). Neurology 2019;92(17):
patients. World Neurosurg 2021;145:e233-e241. e1948-e1956. doi:10.1212/
doi:10.1016/j.wneu.2020.10.008 WNL.0000000000007365
33 de Oliveira Manoel AL, Mansur A, Silva GS, et al. 44 Maciel CB, Barden MM, Youn TS, et al.
Functional outcome after poor-grade Neuroprognostication practices in postcardiac
subarachnoid hemorrhage: a single-center study arrest patients: an International Survey of Critical
and systematic literature review. Neurocrit Care Care Providers. Crit Care Med 2020;48(2):
2016;25(3):338-350. doi:10.1007/s12028-016- e107-e114. doi:10.1097/CCM.0000000000004107
0305-3
45 Moseby-Knappe M, Westhall E, Backman S, et al.
34 van der Steen WE, Leemans EL, van den Berg R, Performance of a guideline-recommended
et al. Radiological scales predicting delayed algorithm for prognostication of poor
cerebral ischemia in subarachnoid hemorrhage: neurological outcome after cardiac arrest.
systematic review and meta-analysis. Intensive Care Med 2020;46(10):1852-1862.
Neuroradiology 2019;61(3):247-256. doi:10.1007/ doi:10.1007/s00134-020-06080-9
s00234-019-02161-9
46 Endisch C, Westhall E, Kenda M, et al. Hypoxic-
35 Egeto P, Loch Macdonald R, Ornstein TJ, ischemic encephalopathy evaluated by brain
Schweizer TA. Neuropsychological function after autopsy and neuroprognostication after cardiac
endovascular and neurosurgical treatment of arrest. JAMA Neurol 2020;77(11):1-10. doi:10.1001/
subarachnoid hemorrhage: a systematic review jamaneurol.2020.2340
and meta-analysis. J Neurosurg 2018;128(3):
47 Beuchat I, Sivaraju A, Amorim E, et al. MRI-EEG
768-776. doi:10.3171/2016.11.JNS162055
correlation for outcome prediction in postanoxic
36 Lissak IA, Locascio JJ, Zafar SF, et al. myoclonus: a multicenter study. Neurology 2020;
Electroencephalography, hospital complications, 95(4):e335-e341. doi:10.1212/
and longitudinal outcomes after subarachnoid WNL.0000000000009610
hemorrhage. Neurocrit Care 2021:1-12.
48 Robinson CP. Moderate and severe traumatic
doi:10.1007/s12028-020-01177-x
brain injury. Continuum (Minneap Minn) 2021;
37 Krzyżewski RM, Kliś KM, Kwinta BM, et al. High 27(5, Neurocritical Care):1277-1299.
leukocyte count and risk of poor outcome after
49 Chou SH. Subarachnoid hemorrhage. Continuum
subarachnoid hemorrhage: a meta-analysis.
(Minneap Minn) 2021;27(5, Neurocritical Care):
World Neurosurg 2020;135:e541-e547. doi:10.1016/
1201-1244.
j.wneu.2019.12.056
50 Adams JH, Doyle D, Ford I, et al, Diffuse axonal
38 Kim W, Choi KS, Lim T, et al. Prognostic value of
injury in head injury: definition, diagnosis and
echocardiography for left ventricular
grading. Histopathology 1989;15(1):49-59.
dysfunction after aneurysmal subarachnoid
doi:10.1111/j.1365-2559.1989.tb03040.x
hemorrhage: a systematic review and meta-
analysis. World Neurosurg 2019;126:e1099-e1111. 51 Abu Hamdeh S, Marklund N, Lannsjö M, et al.
doi:10.1016/j.wneu.2019.03.054 Extended anatomical grading in diffuse axonal
injury using MRI: hemorrhagic lesions in the
39 Scarpino M, Lolli F, Lanzo G, et al. Does a
substantia nigra and mesencephalic tegmentum
combination of ≥2 abnormal tests vs. the
indicate poor long-term outcome. J Neurotrauma
ERC-ESICM stepwise algorithm improve
2017;34(2):341-352. doi:10.1089/neu.2016.4426
prediction of poor neurological outcome after
cardiac arrest? A post-hoc analysis of the 52 Montellano FA, Ungethüm K, Ramiro L, et al. Role
ProNeCA multicentre study. Resuscitation 2021; of blood-based biomarkers in ischemic stroke
160:158-167. doi:10.1016/j. prognosis: a systematic review. Stroke 2021;
resuscitation.2020.12.003 52(2):543-551. doi:10.1161/STROKEAHA.120.029232
40 Carrick RT, Park JG, McGinnes HL, et al. Clinical
predictive models of sudden cardiac arrest: a
survey of the current science and analysis of
model performances. J Am Heart Assoc 2020;
9(16):e017625. doi:10.1161/JAHA.119.017625
1428 OCTOBER 2021

53 Streitberger KJ, Leithner C, Wattenberg M, et al. 59 Wahlster S, Sharma M, Chu F, et al. Outcomes
Neuron-specific enolase predicts poor outcome after tracheostomy in patients with severe acute
after cardiac arrest and targeted temperature brain injury: a systematic review and
management: a multicenter study on 1,053 meta-analysis. Neurocrit Care 2021;34(3):
patients. Crit Care Med 2017;45(7):1145-1151. 956-967.
doi:10.1097/CCM.0000000000002335 doi:10.1007/s12028-020-01109-9
54 Luoto TM, Raj R, Posti JP, et al. A systematic 60 Edlow BL, Claassen J, Schiff ND, Greer DM.
review of the usefulness of glial fibrillary acidic Recovery from disorders of consciousness:
protein for predicting acute intracranial lesions mechanisms, prognosis and emerging therapies.
following head trauma. Front Neurol 2017;8:652. Nat Rev Neurol 2021;17(3):135-156. doi:10.1038/
doi:10.3389/fneur.2017.00652 s41582-020-00428-x
55 Garg A, Soto AL, Knies AK, et al. Predictors of 61 Curing Coma. Accessed August 10, 2021.
surrogate decision makers selecting curingcoma.org/home
life-sustaining therapy for severe acute brain
62 Elmer J, Coppler PJ, May TL, et al. Unsupervised
injury patients: an analysis of US population
learning of early post-arrest brain injury
survey data. Neurocrit Care 2021. doi:10.1007/
phenotypes. Resuscitation 2020;153:154-160.
s12028-021-01200-9
doi:10.1016/j.resuscitation.2020.05.051
56 Williamson T, Ryser MD, Ubel PA, et al.
63 Wendler D. A call for a patient preference
Withdrawal of life-supporting treatment in
predictor. Crit Care Med 2021;49(6):877-880.
severe traumatic brain injury. JAMA Surg 2020;
doi:10.1097/CCM.0000000000004949
155(8):723-731. doi:10.1001/jamasurg.2020.1790
64 Goostrey KJ, Lee C, Jones K, et al. Adapting a
57 Quinn T, Moskowitz J, Khan MW, et al. What
traumatic brain injury goals-of-care decision aid
families need and physicians deliver: contrasting
for critically ill patients to intracerebral
communication preferences between surrogate
hemorrhage and hemispheric acute ischemic
decision-makers and physicians during outcome
stroke. Crit Care Explor 2021;3(3):e0357.
prognostication in critically ill TBI patients.
doi:10.1097/CCE.0000000000000357
Neurocrit Care 2017;27(2):154-162. doi:10.1007/
s12028-017-0427-2 65 Muehlschlegel S, Hwang DY, Flahive J, et al.
Goals-of-care decision aid for critically ill
58 Jones K, Quinn T, Mazor KM, Muehlschlegel S.
patients with TBI: development and feasibility
Prognostic uncertainty in critically ill patients
testing. Neurology 2020;95(2):e179-e193.
with traumatic brain injury: a multicenter
doi:10.1212/WNL.0000000000009770
qualitative study. Neurocrit Care 2021.
doi:10.1007/s12028-021-01230-3

2021 - Brain Death - Death by Neurologic Criteria Determination

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Neurologic Outcome REVIEW ARTICLE

Intensive Care Unit 

RECENT FINDINGS:Striving to maintain a high prediction performance during

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Surviving a severe acute illness to intensive care unit admission is the

THREATS TO ACCURATE NEUROPROGNOSTICATION

Imprecision of Diagnostic Methods and Uncertainties in Clinical

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A 94-year-old woman with hypertension presented to the emergency CASE 10-2

This case demonstrates another example of the important effect of COMMENT

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neurologic prognosis, or death due to withdrawal of life support because of

American Spinal Injury Association Impairment Scale (AIS)11,a

A Complete. No sensory or motor function is preserved in the sacral segments S4-5.

Modified Rankin Scale12,b

CONTINUED ON PAGE 1411

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Limitations of Outcome Assessments and Prognostic Models

CONTINUED FROM PAGE 1410

Glasgow Outcome Scale – Extended13,c

Glasgow-Pittsburgh Cerebral Performance Category Scale14,d

5 Brain death: apnea, areflexia, EEG silence, etc.

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Multimodal Characterization of Injury Burden Using Prognostic Tools

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● Bilaterally absent corneal

the level of disability that is perceived as unacceptable. But no neuroprognostic

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CLINICAL EXAMINATION. The clinical examination can provide critical prognostic

NEUROPHYSIOLOGIC TESTS. Neurophysiologic tests yield diagnostic and prognostic

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NEUROIMAGING. Many scales exist to classify head CT findings and their

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COMMENT In this case, the degree of encephalopathy was initially perceived as a

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limitations hinder their widespread use, including a lack of broad availability

Cerebral Reserve and Resilience

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as much as possible; failure to do so may be perceived as frustrating to families.58

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in key knowledge gaps, from developing novel therapies and identifying

COMMENT In cases of new-onset refractory status epilepticus (NORSE), the

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VIDEO 10-3 VIDEO 10-4

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