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Original Article

Pathophysiology and Management of


Moderate and Severe Traumatic
Brain Injury in Children

Journal of Child Neurology


2016, Vol. 31(1) 35-45
The Author(s) 2014
Reprints and permission:
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DOI: 10.1177/0883073814562626
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Kristin Guilliams, MD1 and Mark S. Wainwright, MD, PhD2,3

Abstract
Traumatic brain injury remains a leading cause of morbidity and mortality in children. Key pathophysiologic processes of
traumatic brain injury are initiated by mechanical forces at the time of trauma, followed by complex excitotoxic cascades
associated with compromised cerebral autoregulation and progressive edema. Acute care focuses on avoiding secondary
insults, including hypoxia, hypotension, and hyperthermia. Children with moderate or severe traumatic brain injury often
require intensive monitoring and treatment of multiple parameters, including intracranial pressure, blood pressure, metabolism, and seizures, to minimize secondary brain injury. Child neurologists can play an important role in acute and long-term
care. Acutely, as members of a multidisciplinary team in the intensive care unit, child neurologists monitor for early signs of
neurological change, guide neuroprotective therapies, and transition patients to long-term recovery. In the longer term, neurologists are uniquely positioned to treat complications of moderate and severe traumatic brain injury, including epilepsy and
cognitive and behavioral issues.
Keywords
pediatric brain trauma, closed head injury, pediatric neurocritical care, intracranial pressure
Received March 11, 2014. Received revised August 26, 2014. Accepted for publication October 14, 2014.

Traumatic brain injury affects approximately 500 000 children


under 14 years of age annually, resulting in approximately
35 000 hospitalizations and over 2000 deaths (www.cdc.gov).
The majority of moderate and severe cases will be admitted
to the hospital and require ICU-level care. Guidelines for the
management of severe traumatic brain injury in children were
updated in 2012.1 These recommendations are hampered by a
dearth of data and include no level I recommendations. The
degree to which these guidelines are followed and the impact
of adherence to the guidelines on outcome are not known.
The care of hospitalized children with traumatic brain
injury requires a multidisciplinary team, including emergency
physicians, critical care physicians, trauma and/or neurosurgeons, and child neurologists. There is increasing recognition
that a cooperative program which implements best practices
for the management of these patients can have a significant
effect on outcomes.2 In this multidisciplinary approach the
child neurologist has an important role in helping to delineate
the extent of the initial injury, to advocate for neuroprotective
management to prevent secondary brain insults, and to help
transition patients from acute to chronic care.3 The emergence
of a field of pediatric neurocritical care with closer collaboration between pediatric intensivists and neurologists is an
important step toward improving therapies for these insults.

The child neurologist who is involved in the acute care of


these patients has a unique perspective on their care through
ongoing involvement with the patient and the family for management of long-term complications including epilepsy and
cognitive or behavioral impairments.
Traumatic brain injury is classified as mild, moderate, or
severe based on initial Glasgow Coma Score. Severe injuries
have a Glasgow Coma Score of 8 or less and compose the
majority of acute care traumatic brain injury research performed thus far. Mild injuries are defined as a Glasgow Coma

Department of Neurology, Division of Pediatric and Developmental


Neurology, and Department of Pediatrics, Division of Critical Care Medicine,
Washington University School of Medicine, St. Louis, MO, USA
2
Ruth D. & Ken M. Davee Pediatric Neurocritical Care Program, Ann & Robert
H. Lurie Childrens Hospital of Chicago, Chicago, IL, USA
3
Department of Pediatrics, Divisions of Neurology and Critical Care Medicine,
Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Corresponding Author:
Kristin Guilliams, MD, Department of Neurology, Division of Pediatric and
Developmental Neurology, and Department of Pediatrics, Division of Critical
Care Medicine, Washington University School of Medicine, 660 S Euclid Ave,
Box 8111, St. Louis, MO 63110, USA.
Email: guilliamsk@neuro.wustl.edu

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Journal of Child Neurology 31(1)

Scale of 14 or 15. This definition of a Glasgow Coma Score of


13 as either a mild or moderate injury has been debated in
pediatric and adult literature.4,5 Within this article, moderate
traumatic brain injury refers to a Glasgow coma score of
9-13. It is important to note that a child less than 2 years of age
with any level of brain injury warrants consideration of possible inflicted traumatic brain injury with a careful clinical
examination, including a fundoscopic exam, to look for other
injuries or signs of abuse, such as bruising or burn marks.6
Children with moderate or severe brain injury warrant acute
imaging to rule out lesions requiring neurosurgical intervention. Computed topography (CT) scans are fast, safe, and
reliable for revealing blood or bone injury. Evidence of skull
fracture, midline shift, or epidural hematoma requires neurosurgical consultation. Importantly, if initial imaging reveals a
surgically operable lesion, such as unilateral edema with mass
effect or hydrocephalus caused by obstructed CSF outflow,
neurosurgical intervention is a top priority.

Pathophysiology of Traumatic Brain Injury


in Children
In trauma, the brain is susceptible to heterogeneous injury.
The immature brain is vulnerable to biomechanical forces,
excitotoxicity, inflammation, and altered autoregulation.
Velocity, contact force, and 3-dimensional angular acceleration of the trauma contribute to the primary injury.7 These
forces can be influenced by age as infant cranial sutures are
able to absorb more strain than adults,8 and developing neck
musculature changes angular acceleration forces. Traumatic
brain injury causes increased extracellular potassium and
glutamate.9 Excessive glutamate activation can cause intracellular calcium overload and cell death,10 which can lead
to further inflammation and edema. Children with traumatic
brain injury also have elevated levels of adenosine, compared
to other children, which can be a neuroprotective response
to counter the elevated glutamate levels, as adenosines A1
receptors decrease glutamate release.11 Giza et al12 have published an eloquent summary of further details of cellular and
physiologic responses to injury as well as recovery as elucidated in pediatric animal models.

Management of Severe Traumatic


Brain Injury
Acute management focuses on minimizing secondary injury
and preventing secondary insults to the brain. Secondary injuries are pathophysiological consequences of the primary
injury, including mitochondrial dysfunction or cytoskeletal
damage. Secondary insults include physiologic derangements
such as hypoxia or hypotension, which exacerbate the underlying primary injury. To guide neuroprotective strategies
aimed at minimizing secondary insults, the Brain Trauma
Foundation synthesized Guidelines for the Acute Medical
Management of Severe Traumatic Brain Injury in Infants,
Children, and Adolescents in 2003.13 More recently, the

updated second edition was released in 2012.1 While pediatric


traumatic brain injury has been an active research area, there
remains a paucity of evidence that meets the rigorous criteria
for the most recent guidelines.1 Several studies included in
the first guidelines were excluded in the second edition. The
majority of the guideline recommendations remain at level III
evidence (case series, databases, or registries or moderate to
poor quality randomized controlled trials or cohorts).

Physiologic Monitoring
Most children with severe traumatic brain injury will be
admitted to a pediatric intensive care unit for physiologic
monitoring to avoid secondary insults including hypoxia,
hypotension and hyperthermia. For children with a Glasgow
Coma Score  8, the guidelines recommend endotracheal
intubation. In addition to mechanical support, these patients
will typically also require arterial cannulation for continuous
blood pressure monitoring. While 90 mmHg or 5th percentile
for age (70 mmHg [2  age in years]) is commonly used as
a lower threshold for systolic blood pressure, maintaining
higher normal to mildly hypertensive blood pressures can be
beneficial. Allowing children to be mildly hypertensive with
systolic blood pressure measurements up to 30 mmHg above
age-corrected normal values has been correlated with lower
mortality rates.14 The main focus of blood pressure measurements in traumatic brain injury, however, is the mean arterial
pressure (MAP [2/3 diastolic] [1/3 systolic]), as it relates
to cerebral perfusion pressure. Cerebral perfusion pressure is
calculated by the difference between mean arterial pressure
and intracranial pressure (CPP MAP ICP). The 2012
guidelines recommend maintaining a minimum cerebral perfusion pressure of 40 mmHg in all patients, independent of
age.1 A number of studies have investigated age-specific
change in intracranial pressure, attempting to establish thresholds associated with good outcome.15,16 Others investigators
have proposed more sophisticated methods for quantifying
the burden of abnormal intracranial pressure or cerebral
perfusion pressure based on time and degree of deviation from
normal values.16,17 However, none of these approaches have
been applied in routine clinical practice.18 A recent multicenter observational cohort study investigated survival rates
following traumatic brain injury based on predefined agespecific cerebral perfusion pressure thresholds.19 Data from
these 2074 cases support a goal cerebral perfusion pressure
above 40 mm Hg in 0- to 5-year-olds and about 50 mm Hg
in 6- to 17-year-olds.
Cerebral autoregulation is often compromised after pediatric traumatic brain injury and is associated with poor outcome.20 In uninjured brains, local control tightly regulates
the cerebrovasculature to maintain a steady cerebral blood
flow over a range of mean arterial blood pressures. If the mean
arterial pressure is either lower or higher than the range of
autoregulation, the cerebral blood flow is dependent on mean
arterial pressure. In adults, the range of autoregulation is
estimated at mean arterial pressure of 50-170 mmHg, and

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Guilliams and Wainwright

37

autoregulatory response can be dependent on vascular tone.21


The upper limit for children is less well established, but the
lower limit is close to that for adults (46-70 mmHg), even for
children under 2 years of age.22 Therefore, even in healthy
children, there is less reserve between the baseline mean arterial pressure and the lower limit of autoregulation. In traumatic
brain injury, autoregulatory mechanisms are often damaged,
causing cerebral blood flow to become more dependent on
blood pressure. Younger children can be at increased risk
for impaired autoregulation.23 Impairment is inconsistent
and can even vary between hemispheres within the same
patient.24 Altered autoregulation is also dynamic, and can
either normalize or worsen over the first few days in the
pediatric intensive care unit.25
Intracranial pressure monitors (external strain gauge transducers, catheter-tip pressure transducer devices, or ventriculostomy catheters) are frequently placed, although indications for
placement currently remain at level III evidence.12 Ventriculostomy catheters have the added advantage of being able to also
drain cerebrospinal fluid. Some transducers, such as the Licox
system (Integra Neurosciences, Plainsboro, NJ) are combined
with other technology to provide information about local tissue
oxygenation (PbtO2). Brain tissue oxygen monitors are generally
placed either in the white matter, as it is more metabolically stable than gray matter, or adjacent to, but not within, the injured
tissue or penumbra. Several studies suggest low brain tissue oxygenation is associated with poorer outcomes and goal-directed
treatment can improve outcomes.26-28 However, oxygenation
thresholds (15-20 mmHg) are based largely on adult data. Age
dependence of the threshold and dose-dependent consequences
of cerebral hypoxia have yet to be determined.
The utility of intracranial pressure monitoring has been
called into question by the results of the BEST TRIP study.29
This was a multicenter controlled trial of 324 patients with
severe traumatic brain injury in Bolivia and Ecuador that
included children older than 13 years and randomized subjects
to invasive monitoring of intracranial pressure or treatment
based on imaging and clinical exam. There was no significant
difference between groups in the primary outcome, a composite measure of cognitive function at 3 months, or in 6-month
mortality. These results suggested that maintaining intracranial
pressures of 20 mm Hg or less conferred no benefit compared
to a combination of care directed by neuroimaging and the
physical exam. The extent to which these results call into question current intracranial pressure-directed care in North America based on the Brain Trauma Foundation guidelines is
controversial.30 The high mortality (39% and 41%) in the study
groups is greater than expected from US studies. More importantly, these results underscore the need to interpret and modify
intracranial pressure in the context of other measures of cerebral blood flow, autoregulation, and cerebral metabolism.31

Intracranial Pressure Lowering Therapies


Numerous studies involving pediatric traumatic brain injury
patients demonstrate an association between intracranial

hypertension and neurologic morbidity or survival.32 Multiple


mechanisms contribute to increased intracranial pressure after
severe traumatic brain injury. Disruption of the blood brain
barrier and impaired cerebral autoregulation can contribute to
vasogenic edema. Necrosis, excitotoxic cell death, or other
metabolic derangements caused by loss of cell wall integrity
and the failure of ATP-dependent ion transporters can cause
or exacerbate cytotoxic edema. Current recommendations
advise maintaining intracranial pressure below 20 mmHg and
cerebral perfusion pressure above 40-50 mmHg. A multifaceted approach can be necessary to gain intracranial pressure
control. Figure 1 gives a stepwise approach to elevated intracranial pressure management.

Patient Positioning
Basic maneuvers can help assist venous drainage from the
cranium and lower intracranial pressure with minimal risk.
Positioning head midline will prevent kinking and obstruction
of the jugular veins. Cervical collars should be appropriately
snug, but not so tight as to impede venous return. Elevating
the head of the bed 30 degrees by flexing the patient at the hip
(not the abdomen) promotes venous drainage. However, if
the patient is hypotensive or hypovolemic, the risk of exacerbating hypoperfusion and ischemia can outweigh benefits of
head elevation.

Sedation and Analgesia


Sedatives and analgesics offer possible benefits of anticonvulsant and antiemetic effects, decreasing shivering, lowering
cerebral metabolic demand, and mitigating long-term psychological trauma and stress.1 There are limited outcome data to
recommend one agent strongly over another. Minimizing
unnecessary noxious stimuli, such as noise, baths, and suctioning, are a helpful first step in keeping a patient calm.
Continuous infusions of midazolam and narcotics, such as
fentanyl or morphine, are commonly used in pediatric intensive care units, and are reported as the sedation and analgesia
agents in several pediatric traumatic brain injury studies when
specific agents are listed.26,33 One report of midazolam in
adult traumatic brain injury, which included teenagers in its
lower age range, suggested that boluses of midazolam did not
decrease, and can even increase, intracranial pressure.34 A
small case series found that etomidate could effectively lower
intracranial pressure without significantly altering blood pressure in children with severe traumatic brain injury.35 However, caution must be observed for the potential side effect
of adrenal suppression with etomidate. Barbituates, such as
thiopental or pentobarbital, can lower intracranial pressure,
but carry risk of hemodynamic suppression and instability.
Ketamine has historically been avoided in brain injury, due
to reports of increased intracranial pressure,36-38 however
other reports suggest that when used in conjunction with an
anesthetic agent, it might not raise, and perhaps might even
decrease intracranial pressure.39-41 Propofol can control

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Journal of Child Neurology 31(1)

Figure 1. Algorithm for clinical management of suspected increased intracranial pressure.

intracranial pressure in pediatric traumatic brain injury,42 but


is not recommended for continuous sedation in children due to
safety warnings from the Food and Drug Administration.

Neuromuscular Blockade
No trials have specifically examined the role of neuromuscular
blockade in pediatric traumatic brain injury for intracranial
pressure control, but neuromuscular blockade can be considered for refractory intracranial hypertension. Potential benefits
include reducing intrathoracic pressure leading to improved
cerebral venous outflow, reducing shivering and posturing, and
decreasing metabolic demand. An adult study examining
potential early use of neuromuscular blockade found that prophylactic use did not add benefit to intracranial pressure control
and added to risk of pneumonia and length of stay in the intensive care unit.43

1 gm/kg) and has limited clinical trials. Mannitol most likely


reduces overall brain water,44 but carries potential side effects
of hypovolemia,45 and renal failure,46 particularly when serum
osmolality exceeds 320 mOsm/L, due to an increased risk of
acute tubular necrosis.47 Hypertonic saline in the pediatric population is usually limited to 3% saline, although adult practices
can use concentrations as high as 23.4%. A slightly higher
osmolar threshold of 360 mOsm/L can be tolerated with hypertonic saline.48,49 A double-blind crossover study reported that
hypertonic saline lowers intracranial pressure and reduces the
total number of other interventions required for intracranial
pressure in children with traumatic brain injury compared to
normal saline (0.9%).50 A recent meta-analysis of adult studies
found a small, but potentially clinically significant advantage
of hypertonic saline over mannitol for controlling intracranial
pressure,51 but with current evidence available, the choice
between mannitol and hypertonic saline remains at the discretion of the treating physician.

Osmotic Therapy
Mannitol and hypertonic saline are hyperosmolar agents often
used to lower intracranial pressure. Mannitol gained early
acceptance and establishment in clinical protocols (typically

Cerebrospinal Fluid Drainage


The Monro-Kellie hypothesis refers to the concept that the
skull is a fixed space filled with brain tissue, cerebrospinal

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Guilliams and Wainwright

39

fluid, and blood,52 and an increase in one component should


cause a decrease in another component. An external ventricular drain for cerebrospinal fluid, allowing for an increase in
swelling brain tissue, can be helpful in lowering intracranial
pressure.1,53

Hyperventilation
Prophylactic, or chronic hyperventilation should be avoided.1,54
Hyperventilation induces hypocarbia (PaCO2 < 35 mmHg),
which leads to cerebral vasoconstriction and a reduction
in cerebral blood flow. As there is rarely excessive cerebral
blood flow in pediatric traumatic brain injury, hyperventilationinduced reduction in cerebral blood flow often leads to
ischemia.55,56 One retrospective study found that children
with 3 or more documented episodes of hypocarbia had an
increased odds ratio of 3.93 for mortality compared to children who remained normocarbic.57 As a temporizing rescue
to counteract impending herniation, hyperventilation can
be used, but only for a brief time until other therapies can
be enacted to control elevated intracranial pressure. The
2012 guidelines recommend advanced neuromonitoring to
specifically investigate possible cerebral ischemia if hyperventilation is used.1

Temperature Control
The adverse effects of fever58,59 and promising results from
animal and early adult studies created optimism for therapeutic hypothermia in the pediatric neurotrauma. However, 3
major clinical trials of hypothermia for pediatric traumatic
brain injury have not demonstrated improvement in outcomes.
The first study of therapeutic moderate hypothermia (32-33 C),
started within 8 hours, failed to demonstrate benefit in longterm outcomes.60 A second large trial, also using moderate
hypothermia within 8 hours, suggested worsened outcomes
and a trend toward increased mortality.61 More recently, the
third major trial was terminated early for futility after interim
analysis.62 Therefore, hypothermia should not be used for
prophylactic management of severe traumatic brain injury.
Brief moderate hypothermia (32-33 C) can be considered to
control elevated intracranial pressures,1 but preferably at a
center with significant experience with cooling and rewarming children.

Corticosteroids
There is no evidence to support steroid use in pediatric traumatic brain injury. In one study, children who received dexamethasone had no benefit in intracranial pressure or 6-month
outcomes compared to children who received placebo.63 The
treatment group also had a trend toward increased incidence
of bacterial pneumonia. The 2012 guidelines specifically recommend against corticosteroid use in severe traumatic brain
injury.1

Decompressive Craniectomy
A decompressive craniectomy with duraplasty is often considered for pediatric traumatic brain injury patients with
medically refractory intracranial hypertension or signs of
herniation.1 Research on decompressive craniectomies in
both children and adults is heterogenous with regard to type
(eg, unilateral, bilateral, subtemporal, frontotemporoparietal)
and timing. This creates difficulty in drawing conclusions
about effectiveness or benefit. One small pilot study of very
early surgery reported lower intracranial pressures and
improved 6-month outcomes in children.64 However, other
studies have not found quite as robust results. A randomized
controlled trial in adults with diffuse injury and refractory
intracranial hypertension found early decompressive craniectomy to lower pressure but have worse 6-month outcomes
compared to controls.65 Further research is needed to clarify
patient selection, timing, and long-term outcomes.

Glucose and Metabolism


Glucose control in severe traumatic brain injury requires a
careful balance between hypoglycemia and hyperglycemia.
Hypoglycemia (<70 mg/dL, or 3.9 mmol/L) is not optimal for
brain metabolism regardless of brain injury, but the lower
limit in traumatic brain injury is difficult to define as the brain
can have an increased demand for glycolysis after injury.66 In
adults, tight glycemic control, keeping systemic glucose
below 120 mg/dL (6.7 mmol/L), is associated with increased
frequency of cerebral hypoglycemia, increased lactate/pyruvate ratios, and glutamate release.67,68 On the contrary, hyperglycemia >300 mg/dL (16.6 mmol/L) was associated with
100% mortality rate in one pediatric traumatic brain injury
cohort.69 An optimal target for blood glucose levels has not
been established, and the current guidelines defer to the treating physician.

Noninvasive Advanced Monitoring


Electroencephalogram (EEG) Monitoring and
Anticonvulsant Therapies
Posttraumatic seizures can cause additional secondary injury
early after traumatic brain injury. The posttraumatic brain can
be excitotoxic due to elevated peak glutamate, glycine, and
aspartate levels.70 Status epilepticus and particularly refractory status epilepticus are associated with a significant
increase in mortality in adults and children.71-74 Nonconvulsive seizures and status epilepticus are often unrecognized
in comatose patients75 and can be detected in up to 50% of
patients in an intensive care unit when examined with continuous EEG monitoring.76-78 The majority of these seizures will
not be detected during a routine EEG and prolonged monitoring is needed.78-80 No standards have been established for the
use of continuous EEG in the children with traumatic brain
injury. However, it is clear that nonaccidental head trauma
(also known as abusive head trauma) is associated with a

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higher incidence of convulsive and nonconvulsive status epilepticus, which require continuous EEG monitoring to guide
effective treatment.81 A recent prospective study of 87 children with mild to severe traumatic brain injury with continuous EEG monitoring identified seizures in 43%, and 16% of
all cases had subclinical seizures.82 Subclinical seizures were
more likely to be found in younger children and children with
abusive head trauma. While there is at present no accepted
standard for its use, the collective results of these studies support the use of continuous EEG in young children following
traumatic brain injury, and particularly in victims of abusive
head trauma.
There are very limited data to guide the use of or selection
of anticonvulsants for the treatment of posttraumatic seizures.
Retrospective and observational studies suggest a benefit of
decreased posttraumatic seizures and survival among patients
treated with phenytoin in the acute phase of injury.83,84 A randomized, double-blinded study of adults with severe injury
showed a benefit of phenytoin for early (<7 days) seizures,
but no benefit for seizure prevention between 8 days and
24 months85 or 90-day mortality.86 A randomized, doubleblinded study compared phenytoin to placebo for the prevention of early posttraumatic seizures in children with moderate
to severe head injury,87 comprising 62% severe traumatic
brain injury cases. In this study, subjects younger than 16
years who had suffered blunt head trauma were randomized
to either IV phenytoin or placebo within 60 minutes of arrival
to the emergency room. Surprisingly, there were no differences between group in the primary endpoint (seizures within
48 hours of drug administration), occurring in 7% of the phenytoin group and 5% of the placebo controls. The study was
limited by the low rate of early posttraumatic seizures, which
was lower than reported in other series. The distinction
between early and late posttraumatic seizures is arbitrary, and
the application of a 7-day window to different ages and
mechanisms of head trauma in children is not based on data.
Routine seizure prophylaxis for 7 days after severe traumatic
brain injury with phenytoin is reasonable. After 7 days, there
is no evidence for benefit. The effects of prolonged treatment
of the mechanisms of epileptogenesis are not known, and
there is the potential for adverse drug reaction. There are no
data to guide the selection of newer anticonvulsants for the
management of posttraumatic seizures or to address the
mechanisms of epileptogenesis.
Near-Infrared Spectroscopy. Light is absorbed at different wavelengths in oxygenated and deoxygenated hemoglobin. This
allows infrared electrodes and sensors to estimate percentage
of deoxygenated blood within a capillary bed. When placed
on the forehead, the probe provides an estimation of global cerebral tissue oxygen saturation. A downward trend can suggest
an inability to supply needed oxygen demands, whereas an
upward trend can suggest either luxury perfusion or a cellular
dysfunction and inability to utilize supplied oxygen. Normal
value ranges have been validated in normal children.88 Recent
correlations of near infrared spectroscopy with CT perfusion

scans89 in adults proffer it as a potential surrogate marker of


cerebral blood flow. Further studies are needed to determine
how to optimally use the data for the care of pediatric traumatic
brain injury.
Transcranial Doppler. Transcranial Doppler measurement can
provide additional information about cerebral blood flow. The
middle cerebral artery is insonated to determine a range of
cerebral blood flow velocities. One caveat is that transcranial
Doppler studies are not always routinely performed and are
highly operator dependent, requiring a well-trained sonographer for interpretable results. A pediatric cohort found
alterations in either end-diastolic velocity or pulsatility index
([peak systolic velocity end diastolic velocity] / mean cerebral blood flow velocity) upon admission to be predictive of
intracranial hypertension.90 However, another pediatric study
found the pulsatility index to have poor correlation to intracranial pressure in children.91 Another potential use for transcranial Doppler is in screening patients with mild to moderate
traumatic brain injury for risk for secondary neurological deterioration. An adult observational prospective study found alterations in diastolic velocity and pulsatility index on admission
to be predictive of secondary neurologic deterioration within a
7-day observation period.92 It is not yet known whether or not
this predictive value holds true in children.

Moderate Traumatic Brain Injury


A moderate traumatic brain injury (Glasgow Coma Score 9-13)
can be challenging to manage as staff and family can have
false reassurance for how well the patient is doing. Children
with moderate brain injury should be hospitalized, and often
benefit from admission to an intensive care unit for close
monitoring. There are no published consensus guidelines on
the management of children with moderate brain injury. However, the principles of neuroprotective strategies used in severe
traumatic brain injury still apply. Urgent imaging can screen for
lesions requiring neurosurgical intervention or characterize the
extent of the injury. Careful, frequent observation of blood
pressure, oxygenation, electrolytes, and neurologic exam can
optimize cerebral metabolism and minimize secondary insults.
Hypotension and hypoxia are common in the early phases and
should be aggressively treated.93 These children remain at risk
for seizures, bleeding, edema, and secondary neurologic deterioration requiring rapid intervention and resuscitative efforts.
A subtle change in the neurologic examination is often the first
clue of deterioration.

Transitioning Out of the Intensive Care Unit


In addition to advocating for neuroprotective strategies and
lending expertise in detailed neurologic examination, child
neurologists are a key part of the acute care management team
because of their role in bridging the patient and family out of
the intensive care unit into the home and outpatient environment. Long-term outcomes of moderate or severe traumatic

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41

brain injury are as heterogeneous as the injuries themselves,


ranging from early mortality to near return to baseline. The
baseline in the developing brain is a moving target; in
young children, the full extent of deficits cannot be apparent
until months or years later after developmental milestones are
not achieved. The majority of children will have still significant cognitive impairment at the time of discharge from a
rehabilitation program.94 Formal neuropsychological testing
assesses postinjury strengths and weaknesses to guide appropriate modifications to optimize return to home and school.
Seizures and seizure-like events are important long-term consequences of brain injury, as almost half of all types of
traumatic brain injury (including mild) have posttraumatic
epilepsy, and one-quarter have nonepileptic events.95 New
anxiety or mood disorders are frequently found in the first few
months after a brain injury,96 and behavioral and educational
difficulties can persist even 10 years postinjury.97 Having
firsthand knowledge of the inpatient history can give tremendous insight into outpatient issues, particularly medication
and symptom management. As a patient leaves the intensive
care unit for either ward or rehabilitative services, the child
neurologist can provide ongoing management and anticipatory guidance of seizures,95,98 spasticity and movement
disorders, autonomic instability,99 cognitive and school challenges,100-102 headaches,103 and sleep disturbances.104

intensive care unit.3 Acute management should include meticulous control of physiology with goal-directed intracranial
pressure and cerebral perfusion pressure therapies. During
this period the child neurologist can help integrate the results
of noninvasive cerebral monitoring, such as EEG, nearinfrared spectroscopy, and transcranial Doppler, with changes
in the neurologic exam and the pathophysiologic processes
leading to tissue injury. Understanding the pathophysiology
of secondary injury is essential to providing an effective
approach to neuroprotection. Finally, the child neurologist
has a unique long-term perspective within the multidisciplinary team caring for these patients in the intensive care unit
by continuing to provide care and guidance to the patient
and his or her family during the long process of recovery
with its attendant complications of epilepsy, cognitive, and
motor deficits.
Author Contributions
KPG and MSW drafted and edited the manuscript.

Declaration of Conflicting Interests


The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship,
and/or publication of this article.

Future Directions
The dearth of new data available to support new recommendations in the revised 2012 Brain Trauma Foundation guidelines highlights the difficulty of studies of severe traumatic
brain injury in children. It is clear that more sophisticated
approaches are needed to integrate intracranial pressure and
cerebral perfusion pressure data with other measures of
cerebral metabolism, as well as other physiologic and biochemical parameters.105,106 The availability of transcranial
Doppler, near infrared spectroscopy, and brain tissue oxygen
monitoring will allow care to be directed at maintaining optimum cerebral metabolism and autoregulation, not solely targeting a specific intracranial pressure value. Although the
prospects for new neuroprotective therapies for pediatric
traumatic brain injury are bleak,107 the advent of comparative
effective research approaches for research has the potential to
advance research in this field without development of new
drugs.108 Many important questions remain, including the
type and timing of neurosurgical interventions, and the optimal use of continuous EEG monitoring and antiseizure
medications. An international, multicenter comparative effectiveness study for severe pediatric traumatic brain injury is
currently in progress (http://www.adapttrial.org/).

Summary and Conclusions


The child neurologist plays an essential role in the acute and
long-term management of moderate and severe traumatic
brain injury and other acute brain injuries in the pediatric

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