Pediatric Head Injury

Executive Summary

• Secondary injury refers to the ongoing cascade of events that occurs in response to the initial injury and involves inflammatory mediators, continued brain cell death, and various metabolic derangements. The impact can be mitigated by early and aggressive management of the patient’s respiratory and cardiovascular status, since hypoxia, hypotension, and hypercapnia all contribute to further brain injury. Secondary injury leads to greater morbidity in pediatric patients than in adults due to factors such as higher brain metabolic demand and limited substrate availability.
• The occurrence of vomiting does not predict TBI. At least one episode of emesis is reported in up to 13% of head-injured patients, most of whom do not have significant intracranial injury unless vomiting is associated with other findings such as altered mental status or loss of consciousness. In one review, clinically important TBI (ciTBI) was only found in 0.2% of patients with isolated vomiting, while 2.5% of children who had vomiting accompanied by other findings had ciTBI.
• However, hematomas in infants, those that are located in a non-frontal region, and those that are larger than 3 cm have been associated with underlying intracranial injury.
• For a 1-year-old child, studies estimate the risk of developing a lethal malignancy from a single CT of the brain is up to 1:1500, compared with 1:5000 for a 10-year-old child.
• Given its superior ability to identify clinically important TBI and more modest CT scan rate, PECARN appears to be the most appropriate CDR for pediatric minor head injury.
• Any child with a GCS less than 13 should receive a cranial CT. In pediatric patients with a GCS of 13-15, follow the PECARN rule with all high-risk patients receiving a CT scan.
• Although consensus guidelines do support restricting strenuous activity and prescribing rest for 24 to 48 hours post-injury, “cocoon therapy” (or strict rest in a darkened room) has been associated with slower symptom resolution in patients when compared to those who adopted a stepwise return-to-activity strategy.
• Leptomeningeal cyst, also called “growing fracture,” is the result of extrusion of the leptomeninges and brain tissue through a defect in the dura, often associated with a skull fracture. Children diagnosed with a skull fracture should be referred for follow-up to be monitored for the development of this complication.

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The impact of traumatic brain injury (TBI) as a leading cause of death and morbidity in the pediatric population cannot be ignored, and significantly impacts any provider who cares for children.

Many children seek care in a variety of venues, and early identification, appropriate diagnostic evaluation, and guidance regarding return to normal activities and athletic participation are critical to optimize the long-term function of each child with a minor head injury.

Moderate to severe head injuries require early aggressive management to enable the child to achieve the best functional outcome possible. The authors review the spectrum of pediatric head injury, current evidence for diagnostic evaluation, and management of TBI.

— Ann M. Dietrich, MD, FAAP, FACEP, Editor

Introduction

Traumatic brain injury (TBI) is a leading cause of death and significant morbidity in the pediatric population. According to the Centers for Disease Control and Prevention, approximately 600,000 pediatric patients with TBI are treated annually in U.S. emergency departments, and an additional 250,000 cases are evaluated in outpatient, non-hospital settings.¹ These numbers do not include patients with mild TBI who may not present for medical care because of minimal post-traumatic symptoms.² Although less than 5% of patients have sustained clinically important intracranial injuries, approximately 62,000 patients are admitted annually for management of TBI. Neurosurgical intervention is required in less than 1% of these children.³ Approximately 5-10% of patients sustain substantial lifelong disability and require intensive therapy at home or placement in a long-term care facility after discharge.⁴ TBI has a significant economic impact due to costs for the initial management of acute injuries and long-term care of disabilities, with estimates being as high as $56.3 billion annually for adult and pediatric patients.⁵

The challenge in the initial assessment of head-injured pediatric patients is to identify the small subset that has sustained an intracranial injury requiring neurosurgical intervention. Computed tomography (CT) remains the gold standard diagnostic modality because it allows for rapid and accurate identification of traumatic brain injuries. Despite the low prevalence of clinically important traumatic brain injury (ciTBI), it is estimated that up to one-third of children presenting after mild TBI undergo a CT.⁶ Clinicians must consider the risks of radiation and the economic impact of indiscriminate use of CT scanning and should strive for a more prudent practice pattern. The goal for medical providers is not only to accurately diagnose patients with an acute traumatic brain injury, but also to minimize the role of secondary injury and to provide for appropriate disposition so that outcomes are optimized.

Etiology

There is a biphasic tendency in the prevalence of TBI: Children younger than 5 years and adults older than 60 years of age have a higher overall risk of TBI. Falls are the most common cause of accidental head trauma in the first two years of life. These occur usually from short heights and onto soft surfaces, and rarely result in intracranial injuries or changes in level of consciousness. Skull fractures, however, are rather common even if intracranial trauma is unlikely.⁷ Epidural hematomas can occur after falls, while acute subdural hematomas more commonly result from higher energy mechanisms, such as motor vehicle accidents, or as a result of non-accidental trauma (child abuse). In children between infancy and 10 years of age, acceleration-deceleration forces resulting from bicycle or car accidents are the common culprits of serious, even fatal, head injury. Head trauma resulting from a direct blow to the head (bicycle falls or sports-related injuries) is becoming more prevalent and, in general, causes local damage, unless this is complicated by a rise in intracranial pressure (ICP) with resultant mass effect and cerebral herniation. Motor vehicle accidents are a more common cause of TBI in adolescents and teens.⁷

Males are more prone to TBIs than females, although this gender gap is closing with more females participating in competitive sports.⁸ Gender also may play a role in mortality after TBI due to hormonal influences on inflammatory mediators. In a retrospective review of the National Trauma Data Bank Research Data Sets from 2007 and 2008, which reviewed cases of blunt trauma patients 18 years of age or younger admitted after isolated, moderate-to-severe TBI, Ley et al found that pubescent female gender predicted lower mortality compared with prepubescent females.⁹ This is the first study to demonstrate this finding, and the authors suggest that perhaps endogenous hormonal differences caused the observed difference in mortality.

Abusive Head Trauma. The term “shaken baby syndrome” was used in the past to describe a pattern of injury that included the triad of subdural hemorrhage, retinal hemorrhage, and rib fractures from vigorous shaking of an infant. This term has largely been abandoned in favor of the term “abusive head trauma” (AHT). Computer and animal models depict the injurious effects of shaking on brain parenchyma.¹⁰ Acceleration and deceleration forces from shaking affect the eyes by setting the vitreous in motion, thereby causing traction and shearing on the retina and the retinal vessels. This leads to retinal hemorrhages, and when the injury is severe, it causes splitting of retinal layers — a condition known as traumatic retinoschisis.

Factors relating to the child, family, and perpetrator contribute to the incidence of AHT.¹¹ Infants, in general, are more vulnerable to AHT due to their size, dependency on caretakers, and their inability to report abuse. Premature or disabled children are also more likely than other children to suffer this type of trauma, perhaps because their caretakers may feel additionally burdened. Niederkrotenthaler et al found in their study that, compared to nonabusive head trauma (NAHT) patients, children with AHT were more likely to be uninsured or covered by government-sponsored health coverage (e.g., Medicaid). In addition, this group had lengthier hospital stays and a higher mortality rate.¹²

A correlation has also been found between the peak of infant crying and incidence of AHT.¹³ Family factors such as younger parental age, family instability (non-married status), military service, and lower socioeconomic status have been found to contribute to a higher risk of pediatric abusive head trauma.¹⁴ Adult characteristics contributing to the risk of AHT include substance abuse, psychiatric disorders, and unreasonable expectations of the child’s behavior.¹⁰ Male caretakers, in particular the child’s father or mother’s boyfriend, are more likely to be perpetrators of AHT.^10,11,15

Pathophysiology of TBI

Primary injury occurs at the time of the initial injury. The exact nature of the forces applied to the brain is determined by the nature of the injury, with direct impact to brain parenchyma resulting from direct blows (falls, sports-related injuries), and diffuse injury resulting from acceleration-deceleration forces (MVAs, AHT), which cause shearing of white-matter tracts, axonal disruption, and cell death. Shear forces may also be transmitted to vascular structures, leading to intracranial hemorrhage.¹⁰ Secondary injury refers to the ongoing cascade of events that occurs in response to the initial injury and involves inflammatory mediators, continued brain cell death, and various metabolic derangements. It is important to note that the impact of secondary injury can be mitigated by vigilant attention to patient vital signs and respiratory status, since hypoxia, hypotension, and hypercapnia all contribute to further brain injury.

Secondary injury leads to greater morbidity in pediatric patients than in adults due to factors such as higher brain metabolic demand and limited substrate availability.¹⁶ Specifically, mechanical trauma leads to disruptive stretching of neuronal cell membranes and axons, causing a temporary ionic disequilibrium. Extracellular potassium increases, NMDA receptors are activated by an indiscriminate glutamate release, and intracellular calcium increases. This causes mitochondrial respiration dysfunction and protease activation and can initiate apoptosis. There is an acute energy crisis when ATP-dependent sodium-potassium transporter pump activity increases in an effort to restore ionic equilibrium, thereby increasing local cerebral glucose demand. This enhanced metabolic demand in the presence of mitochondrial dysfunction leads to the use of glycolytic pathways for energy instead of aerobic metabolism. Lactate accumulates extracellularly as a result of this hyperglycolysis, and the resulting acidosis worsens membrane permeability, ionic disequilibrium, and cerebral edema.^8,16

Severe TBI also changes cerebral blood flow (CBF), leading to a triphasic response that has been well-described. On post-injury day 0, patients experience hypoperfusion, on days 1 to 3 hyperperfusion can be expected, and on days 4 to 15 vasospasm can be encountered.¹⁶ Other studies show that with mild TBI, CBF immediately post-injury remains decreased for variable amounts of time, depending on the severity of the injury. In pediatric patients with mild TBI, studies show that CBF actually increases during the first day after mild TBI, and then decreases for many days afterward. There is an impaired autoregulation in CBF in the pediatric population, and in severe TBI it is associated with worse long-term outcomes.¹⁷

Clinical Features

Certain clinical features have been associated with the likelihood of TBI in children, based on observational studies.¹⁸

Historical features:

• Obtain a detailed history from caregivers, witnesses, or EMS personnel.¹⁹ A history should also be obtained from the patient if conscious and if developmental level allows.²⁰
• History should focus on mechanism and timing. Important historical mechanistic features include: height and surfaces of falls, description of object struck with, protective devices used (seatbelts or helmets), speed of vehicle, vehicle damage, injuries to other occupants or airbag deployment in patients involved in motor vehicle accidents.²⁰
• A history incompatible with the child’s age and development may be suggestive of abusive trauma (i.e., a 3-week-old rolled off the bed).¹⁹
• Important features to inquire about include: loss of consciousness and duration, headache, nausea, vomiting, visual disturbances, amnesia, or confusion. Symptoms and their progression or resolution are important to guide management in relationship to the time of injury and subsequent temporal changes or persistence of symptoms. Worsening of symptoms is suggestive of possible intracranial injury, while persistence of symptoms may be more consistent with concussion.¹⁹
• Symptoms of mild traumatic brain injury (mTBI) or concussion are broad and can include: headache, nausea, vomiting, balance problems, dizziness, visual problems, fatigue, sensitivity to light, sensitivity to noise, numbness, tingling, feeling mentally “foggy,” feeling slowed down, difficulty concentrating, difficulty remembering, irritability, sadness, emotional lability, nervousness, drowsiness, or change in sleeping pattern.²¹
• Loss of consciousness (LOC): LOC may occur in up to 39% of patients with head injury. However, when the LOC is brief and isolated and not associated with any other symptoms or signs, the risk of TBI is low, ranging from 0-2.5%.^22-23
• Post-Traumatic Seizure: Only 50% of children with a seizure after head injury have an abnormality on CT scan. Injuries most commonly seen are subdural hematoma, depressed skull fracture, and intracranial laceration.²⁴
• Vomiting: Although distressing for both parent and child, the occurrence of vomiting does not predict TBI. At least one episode of emesis is reported in up to 13% of head-injured patients, most of whom do not have significant intracranial injury unless vomiting is associated with other findings such as altered mental status or LOC.³ In one review, clinically important TBI was only found in 0.2% of patients with isolated vomiting, while 2.5% of children who had vomiting accompanied by other findings had ciTBI.²⁵
• Headache: Headache is a common presenting symptom in older children able to verbalize and localize their discomfort. Younger, preverbal children who have sustained a TBI may present with nonspecific complaints such as vomiting, intractable crying, or increased fussiness.

Physical Exam Findings

• Physical exam should focus on rapid assessment of ABCs (airway, breathing, and circulation).
• In children with a potentially clinically significant head injury, place a properly fitted cervical collar for potential cervical spine injury until cervical injury can be ruled out by imaging or clinical decision rule.
• Assess GCS at first evaluation. (See Table 1.)
• The neurological exam is often the most difficult part of the evaluation due to the inability or unwillingness of some children to comply with the exam. Enlisting the assistance of the parents can be helpful. Assess level of consciousness by gently arousing a sleeping child. Allow an agitated child time to calm down before proceeding with the exam.
• Scalp Hematoma: Isolated scalp hematomas in older children without other worrisome clinical signs are usually not associated with ciTBI. However, hematomas in infants, those that are located in a non-frontal region, and those that are larger than 3 cm have been associated with underlying intracranial injury.²⁵ A scalp hematoma in a child younger than 2 years of age is associated with an increased risk of skull fracture and intracranial hemorrhage.¹⁹
• Ophthalmologic findings: An ophthalmologic exam should be performed to evaluate for retinal hemorrhages, which can be a sign of AHT. Retinal injuries are estimated to be present in 65-90% of cases of AHT.²⁶ Retinal hemorrhages are more likely to be bilateral, cover the macula, and extend to the periphery of the retina in abusive head trauma compared to accidental trauma.²⁷ An evaluation by an ophthalmologist is helpful to assess for retinal hemorrhages when AHT is considered.¹⁹
• Fontanel fullness may indicate increased intracranial pressure in infants. Ears should also be evaluated for hemotympanum, and the nose for cerebrospinal fluid leak. Periorbital ecchymosis (“raccoon eyes”) (see Figure 1) and ecchymosis behind the ears (Battle sign) (see Figure 2) are rare but pathognomonic for basilar skull fracture.

Diagnostic Studies

CT remains the gold standard for the diagnosis of intracranial injury in pediatric patients with head trauma. The occurrence of intracranial lesions is rare in children (< 1%), but represents a “can’t miss diagnosis.”²⁸ However, ionizing radiation from CT carries an increased lifetime malignancy risk. For a 1-year-old child, studies estimate the risk of developing a lethal malignancy from a single CT of the brain of up to 1:1500, compared with 1:5000 for a 10-year-old child.²⁹ In addition, many children require sedation to obtain an adequate study, and this carries its own risks.³⁰ Between 1995 and 2005, cranial head CT rates more than doubled in the United States. Recent data, however, have shown a trend toward a modest decrease in age-adjusted CT rate, possibly due to a more widespread awareness of the potential health risks imposed by radiation exposure from CT. There is no identifiable correlation between CT rate and hospital-specific rates of intracranial hemorrhage, admission, and return visits.⁶ Several clinical decision rules (CDR) have been developed to help identify the risk of ciTBI in children, although none have been widely implemented. CATCH, CHALICE, and PECARN are three high-quality rules that show promise for increasing recognition of traumatic brain injury and reducing the frequency of cranial CT scans and, thus, radiation exposure and sedation risks.^30,31

CATCH

Canadian Assessment of Tomography for Childhood Head Injury (CATCH) was developed by the Pediatric Emergency Research Canada group. It used data derived from 3866 patients from 10 Canadian tertiary pediatric emergency departments who presented with blunt head trauma and a GCS of 13 or greater.

CATCH (see Table 2) is the only clinical decision rule that performed with 100% sensitivity for its primary outcome during its derivation study, although its CT rate approached 50%.³⁰ This high CT rate resulted in a low specificity that is likely due to the inclusion of the criteria of large, boggy hematoma and all motor vehicle crashes. When applied to a recent cohort in Denver, CATCH’s sensitivity was reduced to 91%, as it missed 2 out of 21 clinically important TBIs.³¹ This questionable accuracy and high CT rate makes the rule unlikely to be useful in the United States in its present form.

CHALICE

Children’s Head Injury Algorithm for the Prediction of Important Clinical Events Rule (CHALICE) (see Table 3) was derived by the U.K. Emergency Medicine Research group using 22,772 patients presenting to both pediatric and mixed emergency departments in the United Kingdom.

The authors of this study calculated that their decision rule had 98% sensitivity and 87% specificity for identifying those with significant pathology. The CHALICE rule seems to be the most conservative of the three CDRs, with a reported CT scan rate of only 14% in the original study. CHALICE has been implemented to varying degrees in the United Kingdom in the form of government-mandated guidelines. A recent comparison of these guidelines (derived from CHALICE) to a local U.K. emergency department’s current protocol did show, however, a significant increased CT rate, mainly due to the inclusion of the criterion “3 or more vomits.” This is likely due to an already low baseline rate of pediatric CT scans performed in the United Kingdom. Despite being the most specific rule, a sensitivity of only 84% for CHALICE has been reported. It missed 3 out of 21 clinically important traumatic brain injuries. It was, however, the most specific of the three rules during one comparison study.³¹

PECARN

Pediatric Emergency Care Applied Research Network (PECARN) rule was derived using 33,875 patients with blunt head trauma from 25 emergency departments in the United States. This represents the largest cohort for derivation of a CDR for pediatric head injury. PECARN uses two separate rules based on age, and sought to identify those patients at low risk for injury. The decision rule is reported as a flow diagram and identifies groups as “CT recommended,” “CT or Observation,” and “CT not recommended,” although some have suggested using high-, intermediate-, and low-risk categories. (SeeTable 4.)

The authors of the initial study reported a sensitivity of 99% and specificity of 54% for patients younger than 2 years, and a sensitivity of 97% and specificity of 59% for those older than 2 years of age.³⁰ These authors suggested that cranial CT rates for minor head injury would decrease by 24% in children younger than 2 years of age and by 20% in those older than 2 years of age with implementation of this algorithm. PECARN differs from the previous decision rules in that its goal was to identify patients for whom a CT was not indicated (low-risk group), while the other two CDRs identified patients for whom CT was strongly suggested. PECARN also identifies high- and intermediate-risk groups for TBI. For the intermediate group, it allows physician discretion or parental preference as to whether to observe the patient or perform a CT. PECARN is also the only CDR to undergo validation on a diverse population in a multicenter study similar in demographics to the derivation population. In this comparison, PECARN was the only rule to pick up all cases of ciTBI and was found to have the second best specificity and second lowest CT scan rate.³¹ PECARN has also been validated in different populations from the initial study, as it was recently applied in an adapted form to an Italian tertiary care pediatric ED with excellent safety and efficacy, as well as a high satisfaction rating by the medical staff.³² Given its superior ability to identify clinically important TBI and more modest CT scan rate, PECARN appears to be the most appropriate CDR for pediatric minor head injury.

CT vs. ED Observation

The use of observation has been shown to significantly reduce the use of CT scans and appears to be a safe strategy for some children with head injury. The rate of delayed diagnosis of intracranial injury, defined as a child with an initial normal GCS and physical exam found to have an intracranial injury on neuroimaging greater than six hours after injury, has been shown to be very low. In a study of approximately 18,000 children out of the Calgary Health region, no child was found to have an intracranial hemorrhage with deterioration of level of consciousness, but five children were found to have a delayed intracranial hemorrhage without a change in level of consciousness (~0.02%).³³ For intermediate-risk pediatric patients with blunt head injury, PECARN gives an option of CT scan vs. observation based on physician experience, multiple isolated findings, worsening signs or symptoms after ED observation, or parental preference. Until recently, little was known about parental preference between CT scan and observation. A recent study was done to address this issue and found that more than half of parents presenting to an ED with a head-injured child were unaware of the increased lifetime malignancy risk of CT scan and initially expected a radiological test to evaluate their child’s head injury. After an educational review of the risks and benefits of immediate CT scan compared to observation, a small majority of parents preferred observation to CT.³⁴ Consideration of cost and convenience had less impact on their decision than the welfare of their child, and those who opted to forego immediate CT did so because of concern about the risks of unnecessary testing and radiation risk. This highlights the role the emergency physician has in the education of patients and caretakers to insure informed decision-making. An open dialogue leads to shared decision-making and, given the risks of obtaining a CT scan, this approach should be pursued as the safest strategy.

A recent study of 1381 pediatric patients with blunt head trauma, showed that for every hour of ED observation, there was a time-dependent decrease in head CT rate across all PECARN risk categories. No cases of clinically significant TBI were missed as a result of observation.³⁵ Routine ED observation of most “intermediate” PECARN risk patients with head injury seems to be safe and has the potential to reduce the number of cranial CT scans performed. The optimal duration of observation has yet to be determined, but a recent study identified useful predictors of TBI as: any delayed headache commencing between 4 and 10 hours since injury; significantly worsening headaches presenting between 2 and 12 hours since injury, vomiting between 6 and 12 hours since injury, and headache without significant changes persisting ≥ 12 hours since injury. From this they created a rule for observation of children with head injury that had a sensitivity of 100% and specificity of 72.1% in detecting cases of clinically important TBI.³⁶ (See Table 5.)

While this rule requires validation and testing in different cohorts, it may provide a useful guideline for clinicians who choose to observe patients after closed head injury.

Ultrasound

It is estimated that 16% of non-trivial head injuries in children are skull fractures. Skull fractures are associated with a four-fold higher risk of intracranial injury and may indicate the need for advanced imaging and early neurosurgical consult.³⁷ History and physical examination findings, other than hemotympanum or “raccoon eyes,” may be unreliable tools for detecting skull fractures and intracranial injuries according to a recent ultrasound study in which physicians estimated the likelihood of underlying fracture before imaging.³⁸ Plain radiographs are no longer recommended due to their low sensitivity; they may miss up to 25% of skull fractures.^39-40 Bedside ultrasound has been shown to be useful for detecting skull fractures in children. Ultrasound is an imaging modality that has become increasingly more available to clinicians evaluating head-injured pediatric patients. It can be performed rapidly, requires no ionizing radiation, and has the additional benefit of being able to detect fractures that can be missed by CT scan, such as those that are minimally or nondisplaced.

In a recent study, clinicians receiving one hour of focused ultrasound training were able to detect skull fractures with a high specificity of 97% and a sensitivity of 88%. One non-depressed skull fracture that was adjacent but not directly underneath an overlying hematoma was not detected by ultrasound.³⁸ A different ultrasound protocol that included scanning over a wider area around a hematoma or other visible external injury may have prevented this error.⁴¹

Ultrasound will likely have an increasing role in the management of head-injured children in the future and may be useful as a screening tool but, at this time, a negative skull ultrasound cannot be used as the sole determinant of whether or not to obtain a head CT scan. However, in an otherwise well-appearing child, a positive skull ultrasound may indicate the need for CT scan to rule out intracranial injury.

Summary of Diagnostic Recommendations

In summary, any child with a GCS less than 13 may benefit from cranial CT. In pediatric patients with a GCS of 13-15, we recommend following the PECARN rule with all high-risk patients receiving a CT scan, while all low-risk patients should be given minor head injury discharge instructions and close follow-up with a pediatrician. Low-risk patients include those with a GCS equal to 15, normal mental status, and no signs of basilar skull fracture. Due to a heightened awareness of the radiation risk CT scan poses to pediatric patients, most of those in the intermediate category should initially be observed, with the exception of patients with other concerning findings or strong parental preference for immediate CT. For patients who undergo observation, it is reasonable to discharge after improvement of symptoms (either headache or dizziness). There also seems to be a strong indication to obtain a CT in those with worsening symptoms, a delayed headache, and vomiting after six hours from the injury. Ultrasound is emerging as a useful technique in assessing for skull fracture and can help risk-stratify the pediatric head-injured patient.^38,41,42

Management

The initial management of a patient with a traumatic brain injury first begins with meticulous attention to the maintenance of the patient’s airway, breathing, and circulation. Children with normal blood pressure and no alterations of consciousness may be managed with supportive care. Those with decreased consciousness (GCS < 9), marked respiratory distress, or hemodynamic instability require advanced airway management to enhance oxygenation and ventilation and prevent aspiration of gastric contents.⁴³ Cervical spine immobilization, when needed, must be maintained during advanced airway procedures. Nasotracheal intubation is not recommended in basilar skull fractures or patients with midface trauma. Rapid sequence endotracheal intubation with pre-oxygenation may be performed with every effort made to secure the airway on first attempt, since the number of attempts at tracheal intubation is directly related to increased morbidity and mortality. There has been concern about the potential for a rise in ICP resulting from succinylcholine and, for a time, rocuronium was recommended since it is a non-depolarizing agent. However, there is insufficient evidence at this time to support use of rocuronium instead of succinylcholine. In addition, succinylcholine has been shown to provide superior intubation conditions over rocuronium and should be the paralytic used unless there are contraindications to its use.⁸ In addition, rocuronium’s longer duration of paralysis makes it a less attractive alternative to succinylcholine.

Of note, hypoxemia leads to worse outcomes and should be prevented. Oxygenation is best monitored using continuous pulse oximetry over arterial blood gases since it provides more timely information. Supplemental oxygen should be administered when necessary to ensure adequate oxygenation. For initial monitoring of ventilation of children with traumatic brain injury, capnography is recommended to monitor end-tidal CO₂ in order to avoid excessive hyperventilation and resultant hypocapnia, thereby leading to vasoconstriction and decreased cerebral perfusion. Severe hypocapnia (PaCO₂ < 30 mmHg) has been associated with increased mortality. Temporary hyperventilation (PaCO₂ reduction to 30-35 mmHg) has been found to be acceptable only in patients with signs and symptoms of impending herniation.⁸ An arterial PaCO₂ of 35-40 mmHg should be the goal. Finally, fluid resuscitation of hypotensive patients can be achieved with the use of isotonic solutions and blood products, as dictated by Advanced Trauma Life Support (ATLS) protocol. Use of hypotonic solutions must be avoided, as they might cause increased cerebral edema and cellular destruction. After this initial resuscitation, the main goal of subsequent therapy should be to prevent secondary injury and further neurological decline.

In order to prevent secondary brain injury, intracranial pressure management is crucial. Raising the head of patients to 30° optimizes cerebral perfusion pressure and leads to a decrease of intracranial pressure (ICP) by improving venous drainage without affecting cerebral blood flow. If the initial head CT is abnormal and the initial GCS score is between 3 and 8, ICP monitoring is recommended in a pediatric intensive care unit at a trauma center. Mannitol and hypertonic saline may be administered to decrease ICP in patients with TBI. In their second edition of the guidelines for management of severe pediatric TBI, Kochanek et al (2012) set forth level II recommendations, based on two controlled, non-randomized trials, stating that hypertonic saline may be considered for the treatment of intracranial hypertension in severe pediatric TBI, at an effective acute dose varying between 6.5 and 10 mL/kg.⁴⁴ There is level III evidence, based on non-experimental descriptive studies, supporting its use as a continuous infusion during the patient’s ICU course. Mannitol, on the other hand, has not been extensively studied in the pediatric population in randomized controlled trials, but has been commonly used to manage elevated ICP in pediatric TBI cases.

Posttraumatic seizures can occur early (less than 1 week) and late (greater than 1 week) after the initial brain injury. The use of prophylactic therapy with anticonvulsants (valproic acid, phenytoin, or carbamazepine) following a severe TBI has been shown to prevent early posttraumatic seizures and is recommended to minimize the occurrence of seizures that would otherwise cause a secondary brain injury by increasing the injured brain’s metabolic demands.⁸ Finally, it is recommended that the glucose levels be maintained at less than 200 mg/dL, as hyperglycemia is a marker for TBI severity and worsens lactic acidosis, thereby leading to poorer outcomes.⁸

Barbiturates may also have a benefit in the management of these patients. In a retrospective cohort study of pediatric patients with refractory intracranial hypertension treated with high-dose barbiturates, Mellion et al found that almost 30% of treated children achieved control of refractory intracranial hypertension (defined as ICP > 20 mmHg despite first-tier therapies), and this control was associated with more favorable long-term outcomes.⁴⁵ Kochanek et al’s guidelines outline level III evidence for the use of etomidate to control intracranial hypertension.⁴⁴ However, concerns about adrenal suppression have limited widespread use. Furthermore, according to the current clinical trial, an avoidance of hyperthermia is recommended in patients with refractory ICP. However, Fraser et al found no benefit from early use of hypothermic therapy in pediatric TBI, and even noted a trend toward increased mortality associated with it in their 17-site randomized controlled trial.⁴⁶ Thus, more research is needed before the use of hypothermic therapy can be widely recommended as therapy for TBI.

Decompressive craniectomy in children with severe TBI and refractory ICP may be considered if some or all of the following criteria are met: diffuse cerebral swelling on CT imaging within 48 hours of injury, no episodes of sustained ICP greater than 40 mmHg prior to surgery, GCS greater than 3 at some point after injury, secondary clinical deterioration, and evolving cerebral herniation syndrome.⁸

There is much published literature as to how to best manage intracranial hypertension in patients with severe TBI. Smith et al discussed the role of emergency department skull trephination for epidural hematomas in awake but deteriorating patients. They found that ED skull trephination done by emergency physicians prior to transfer out of the ED resulted in shorter time to relief of elevated ICPs in these “talk-and-deteriorate” patients with CT-proven EDH with anisocoria. However, no difference was found in their neurologic outcomes.⁴⁷

A literature review of non-neurosurgeon drainage of epidural hematomas prior to transferring patients to neurosurgical care was performed using EMBASE, the Cochrane Library, and the Emergency Medicine Abstracts database.⁴⁸ The conclusions were that burr hole drainage by non-neurosurgeons seems to result in favorable outcomes for these patients, including a reversal or stabilization of a herniation syndrome, and should be part of an emergency physician’s training. A retrospective study encompassing a three-year period supports the use of early decompressive craniectomy in pediatric TBI patients to manage intracranial hypertension, rather than making this surgical treatment a last resort in these children’s care.⁴⁹ On the other hand, Sahuquillo concludes in his Cochrane review that secondary decompressive craniectomy ought to be used as a last resort — as a “rescue therapy” — for patients in whom optimal medical management for ICH has failed to control intracranial hypertension.⁵⁰ The one randomized, controlled, single-center trial discussed in this Cochrane review was done in the pediatric population, and it showed that decompressive craniectomy resulted in improved ICP control and mortality, and favorable functional outcomes. Still, the author concludes that this surgical intervention should be left as a rescue therapy once all the medical therapies have failed to achieve control of ICP in TBI patients. Finally, the recent DECRA (Decompressive Craniectomy in patients with severe TBI) study authors discovered that 70% of the early decompressive craniectomy group had unfavorable outcomes compared with 51% of the standard medical care group (p = 0.02). However, as Honeybul et al point out in their recent analysis of DECRA’s data, a transient and mild increase in ICP (> 20 mmHg for 15 minutes as recruitment criterion) might not imply significant ongoing secondary brain injury, and, therefore, no benefit was seen in this population with decompressive craniectomy.⁵¹

Given much controversy and debate over the optimal use of decompressive craniectomy to treat severe TBI patients, and literature reporting both support for and caution against this procedure (done by neurosurgeons or emergency physicians), further study is needed. An ongoing trial (RESCUEicp) may yield insight into the role of this surgical intervention when ICP continues to rise in TBI patients. Regardless, pediatric neurosurgeons should be consulted for all cases of intracranial injury and for open, multiple, or depressed skull fractures. There is some variation in the management of simple, linear skull fractures, with some advocating for admission while others suggest discharge with appropriate follow-up. Consultation with a specialist is still recommended to guide final disposition. In cases of skull fractures with CSF leakage, pneumococcal vaccination in unvaccinated children and prophylactic antibiotics should be administered.⁵² (See Table 6 for a summary of the management of moderate to severe TBI.)

Additional Aspects

Potential Complications. Concussion. Clinically significant brain injury in the absence of radiographic findings of head injury can occur after trauma and is often called “postconcussive syndrome” or concussion. The American Academy of Neurology (AAN) defines concussion as “a trauma-induced alteration in mental status that may or may not involve a loss of consciousness.”⁵³ Symptoms can be subtle and are variable from patient to patient. They are broadly divided into the following categories:^54,55

Somatic: nausea, headache, fatigue, sleep disturbance, visual changes, tinnitus, dizziness, balance problems, light or sound hypersensitivity;

Emotional/Behavioral: increased irritability, emotional lability, depression, anxiety, clinginess, personality changes;

Cognitive: lowered response time, slowed or hesitant thinking, mental “fogginess,” poor concentration, distractibility, memory/learning difficulty, disorganization, problem-solving difficulties.

Specifically in relation to concussion due to sports injury, posttraumatic amnesia (PTA) is important prognostically, as it may be associated with worse functional outcome. PTA of any duration is associated with a greater incidence of dizziness, and PTA lasting more than 30 minutes can indicate a more severe concussion.^55-57 Symptoms of concussion usually resolve within 7 to 10 days, although the recovery time may be prolonged in children.⁵⁸ Numerous recommendations on the management of concussion have been published, and are beyond the scope of this article. In general, optimal ED management requires accurate identification of patients with concussion, appropriate follow-up instructions, and referrals for neurocognitive testing. Although consensus guidelines do support restricting strenuous activity and prescribing rest for 24 to 48 hours post-injury,⁵⁹ “cocoon therapy” (or strict rest in a darkened room) has been associated with slower symptom resolution in patients when compared to those who adopted a stepwise return-to-activity strategy.⁶⁰

Cognitive and Behavioral Dysfunction

In the past, it was believed that children were more likely to recover from TBI due to their greater capacity for neuroplasticity. However, it has been determined that the effects of TBI are actually more long-term than those seen in adults. Since the pediatric brain is still developing, skills are being acquired, and neuronal pathways are being sculpted, any injury during this early period can have effects into adulthood. TBI in childhood may disrupt development of neurobehehavioral skills, with residual deficits manifesting years after the initial injury. Damage to the brain in very young children may impact not only currently established behavioral and intellectual capacity, but the ability to acquire new skills later in life. Cognitive outcome, as measured by IQ, is lower in patients who had a TBI in early childhood.⁶¹ This is in contrast to adults whose IQ largely remains intact after injury.⁶² Pediatric patients who sustain moderate to severe TBI are also at risk for the development of behavioral disorders. An increased rate of hyperactivity, conduct disorder, and poor self-control has been reported in children following head injury.⁶³ Psychosocial factors that put children at risk for sustaining traumatic brain injury also were found to impact recovery, with the development of social, behavioral, and cognitive deficits being associated with lower socioeconomic status. Intervention during the recovery period is vital to maximize the chance that the child makes some developmental gains despite their brain injury.

Chronic Post-traumatic Headache (CPTH)

One of the most common sequelae of TBI is chronic headache, which can persist months after injury and can be seen in up to 43% of patients after head trauma.⁶⁴ This can further debilitate a child already suffering from cognitive deficits, behavioral disorders, and other complications of the initial brain injury. CPTH is typically described as tension-type and episodic, occurring as frequently as twice per week. These headaches can be severe enough to disrupt daily activities and may lead to missed school days (and work days for parents). However, most cases follow a benign course and can be managed conservatively with symptomatic treatment. Complete resolution of headaches can be expected by 12 months.

Leptomeningeal cyst, also called “growing fracture,” is the result of extrusion of the leptomeninges and brain tissue through a defect in the dura, often associated with a skull fracture. Children diagnosed with a skull fracture should be referred for follow-up to be monitored for the development of this complication.

Central Diabetes Insipidus

Central diabetes insipidus (CDI) is a complication of TBI both in adults and pediatric patients. There are limited data on the incidence of CDI in children with TBI, but one retrospective study reported an incidence of 18% in their study population.⁶⁵ This is consistent with reported prevalences in adults, which range from 3%-26%. Central diabetes insipidus is defined as polyuria for at least two consecutive hours (urine output > 4 mL/kg/hr for children weighing less that 70 kg or > 300 mL/hr for larger children), hypernatremia (serum Na > 145 mmol/L), high serum osmolality (> 300 mOsm/kg), and low urine osmolality (< 300 mOsm/kg). The development of CDI early in the acute post-injury period is a poor prognostic sign, with mortality rates as high as 100%, compared to 14% in head-injured patients who do not develop this complication. It is likely a result of damage to the pituitary gland, based on autopsy findings of patients who ultimately died of blunt head injury.⁶⁶ Treatment of CDI includes desamino-8-D-arginine vasopressin or vasopressin infusion and management of increased intracranial pressure, which may include thiopental coma and surgical decompressive craniectomy.

Second Impact Syndrome

Although rare, fatal cerebral edema can develop after relatively minor head trauma if the trauma occurs while a patient is recovering from a prior injury and is still symptomatic. This scenario is referred to as “second impact syndrome.” The second blow to the head can be trivial. However, the patient can suffer neurological deterioration within seconds to minutes after impact due to diffuse cerebral swelling which results from increased cerebral blood volume (due to loss of autoregulation) and posttraumatic catecholamine release. In one review, only 17 cases were described, and all patients were 13-18 years of age. The prognosis for this condition is dismal. Potential interventions include osmotic agents. Surgery has no role.⁶⁷

Pitfalls

Abusive head trauma is a “can’t miss” diagnosis. Clinicians should be vigilant in screening for abusive head trauma because children who are returned to abusive homes are at high risk of suffering further injury and have a higher mortality rate. An evaluation for abuse should at least be considered when assessing any child younger than 2 years of age with TBI. In one study, 28% of patients with a missed diagnosis of abusive head trauma were reinjured. Nine percent of these ultimately died. Of note, children with missed AHT were significantly younger than those children whose AHT was correctly identified (mean age 180 days vs 278 days).⁶⁸

Healthcare providers may be hesitant to initiate an abuse evaluation due to concerns about parental stress, compromise of the physician-patient relationship, cost considerations, increased length of hospitalization, and increased exposure of the child to radiation from additional imaging studies.⁶⁹ A search for concomitant injuries suspicious for abuse will aid this decision-making process, as will identification of historical factors that may suggest abuse (delay in seeking care, multiple versions of history, history that is not developmentally appropriate for age of child, etc.).

An especially important historical factor is a report of a “sentinel injury” or a relatively minor injury noted previously by a parent or caretaker, such as scleral hemorrhage, frenulum tears, and facial bruising in otherwise immobile infants. In one study, 27.5% of children ultimately found to be victims of physical abuse had a previous sentinel injury reported by parents.⁷⁰ A more liberal approach to the use of CT and other radiographic modalities, such as skeletal survey, was recommended when a sentinel injury was reported in order to prevent further injury through early detection. If a skull fracture is detected either by CT or ultrasound in a child younger than 12 months, there must be a heightened suspicion for physical abuse. In one study, 5.6% of infants with apparently isolated skull fractures had additional fractures identified on skeletal survey.⁷¹

Concomitant injuries should also be excluded in patients with TBI because they are associated with worse clinical outcomes. Practitioners assessing injured patients in the emergency department should be thorough in the secondary survey of patients with TBI to avoid missing serious concomitant injuries. In one study of head-injured pediatric patients admitted to the pediatric intensive care unit, 63% sustained serious concomitant injuries, with the chest being the most common extracranial region injured.⁷² Somewhat surprisingly, only 3% had a concomitant neck injury. Patients with additional injuries were older children, those with higher BMIs, and those who had been involved in motor vehicle crashes. Significantly increased infection rates, a higher rate of acute CDI, and a doubling of ICU and hospital lengths-of-stay were seen in this group with missed concomitant injuries. A severe head injury may be deemed less serious, or even missed, in a patient with multiple trauma, such as that seen in the Waddell’s triad, a rare injury pattern that consists of chest-abdomen trauma, leg injury (typically femur fracture), and head injury. This is usually a result of a high-velocity injury such as a child pedestrian struck by a motor vehicle.⁷³

Disposition

Criteria for admission of children with head trauma include the following:

• Intoxication with substances that prevents adequate neurologic examination;
• Suspected or documented child abuse;
• Unreliable caregiver or poor social situation (i.e., unable to properly observe child at home);
• Abnormal CT scan findings, other than isolated skull fractures, warranting admission for observation or neurosurgical intervention;
• Coma, altered mental status, or seizures;
• Focal neurologic deficit;
• Underlying pathology such as coagulopathy or hydrocephalus.

Admission is also recommended for patients with a normal initial CT scan who remain symptomatic requiring antiemetics, intravenous fluid hydration, or pain control.

Data suggest that children with GCS scores of 14 or 15 and a normal initial CT scan can be discharged for observation at home rather than admission to the hospital for neurologic observation.⁷⁴ Neurologic deterioration and need for neurosurgical intervention after an initial negative CT scan is rare.⁷⁵ Therefore, transfer to a Level 1 trauma center with pediatric neurosurgical capabilities should be limited to those patients with positive CT findings.

Return to School. Children with TBI may need special education services for a period of time after the injury. Planning is best done with input from parents, educators, primary care physicians, and (as needed) neuropsychiatric specialists.

REFERENCES

1. Centers for Disease Control and Prevention. Injury Prevention & Control: Traumatic Brain Injury Data and Statistics 2014. Available at http://www.cdc.gov/TraumaticBrainInjury/factsheets_reports.html. Accessed June 5, 2014.
2. Gordon KE, Dooley JM, Wood EP. Descriptive epidemiology of concussion. Ped Neurology 2006;34(5):376-378.
3. Kuppermann N, Holmes JF, Dayan PS, et al. Pediatric Emergency Care Applied Research Network (PECARN), Identification of children at very low risk of clinically-important brain injuries after head trauma: A prospective cohort study. Lancet 2009;374:1160-1170.
4. Cakmachi H. Essentials of trauma: Head and spine. Pedatri Radiol 2009;39 Suppl 3:391-405.
5. Schneier AJ, Shields BJ, Hostetler SG, et al. Incidence of pediatric traumatic brain injury and associated hospital resource utilization in the United States. Pediatrics 2006;118(2):483-492.
6. Mannix R, Meehan WP, Monuteaux MC, et al. Computed tomography for minor head injury: Variation and trends in major United States pediatric emergency departments. J Pediatr 2012;160:136-139.
7. Mihic J, Rotim K, Marcikic M, et al. Head injury in Children. Acta Clin Croat 2011;50(4):539-548.
8. Hu CF, Fan HC, Chang CF, et al. Current approaches to the treatment of head injury in children. Pediatr Neonatol 2013;54(2):73-81.
9. Ley EJ, Short SS, Liou DZ, et al. Gender impacts mortality after traumatic brain injury in teenagers. Trauma Acute Care Surg 2013;75:682-686.
10. Herman BE, Makoroff KL, Corneli HM. Abusive head trauma. Pediatr Emerg Care 2011;27:65-69.
11. Liley W, Stephens A, Kaltner M, et al. Infant abusive head trauma: Incidence, outcomes and awareness. Aust Fam Physician 2012;41:823-826.
12. Niederkrotenthaler T, Xu L, Parks SE, et al. Descriptive factors of abusive head trauma in young children - United States, 2000-2009. Child Abuse Negl 2013;37:446-455.
13. Barr RG, Runyan DK. Inflicted childhood neurotrauma: The problem set and challenges to measuring incidence. Am J Preventive Medicine 2008;34(4 Suppl):S106-S111.
14. Keenan HT, Runyan DK, Marshall SW, et al. A population-based comparison of clinical and outcome characteristics of young children with serious inflicted and noninflicted traumatic brain injury. Pediatrics 2004;114(3):633-639.
15. Paiva WS, Soares MS, Amorim RL, et al. Traumatic brain injury and shaken baby syndrome. Acta Med Port 2011;24:805-808.
16. Shrey CW, Griesbach GS, Giza CC. The pathophysiology of concussions in youth. Phys Med Rehabil Clin N Amer 2011;22(4):577-602.
17. Chaiwat O, Sharma D, Udomphorn Y, et al. Cerebral hemodynamic predictors of poor 6-month Glasgow Outcome Score in severe pediatric traumatic brain injury. J Neurotrauma 2009;26(5):657–663.
18. Pandor A, Goodacre S, Harnan S, et al. Diagnostic management strategies for adults and children with minor head injury: A systematic review and an economic evaluation. Health Technol Assess 2011;15(27):1-202.
19. Hung GR. Minor Head Injury in Children. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 2011: 888-892.
20. Wing R, James C. Pediatric head injury and concussion. Emerg Med Clin North Am 2013;31:653–675.
21. Atabak SM. Updates in the general approach to pediatric head trauma and concussion. Pediatr Clin North Am 2013;l60:1107–1122.
22. Lee LK, Monroe D, Bachman MC, et al. TBI working group of PECARN. Isolated loss of consciousness in children with minor blunt head trauma. JAMA Pediatr 2014;168(9):837-843.
23. Palchak MJ, Holmes JF, Vance CW, et al. Does an isolated history of loss of consciousness or amnesia predict brain injuries in children after blunt head trauma? Pediatrics 2004;113(6):e507-e513.
24. Hauda WE. Trauma in Children. Tintinalli’s Emergency Medicine: A Comprehensive Guide. 2011:1676-1683.
25. Dayan PS, Holmes JF, Atabaki S, et al. Association of traumatic brain injuries with vomiting in children with blunt head trauma. Ann Emerg Med 2014;63(6);657-665.
26. Squier W. The “shaken baby” syndrome: Pathology and mechanisms. Acta Neuropathol 2011;122:519-542.
27. Bechtel K, Stoessel K, Leventhal J, et al. Characteristics that distinguish accidental from inflicted head injury in young hospitalized children. Pediatrics 2004;114:165-168.
28. Fabbri A, Servadei F, Marchesini G, et al. Analysis of different decision aids for clinical use in pediatric head injury in an emergency department of a general hospital. J Trauma 2011;70 (5):e79-e83.
29. Kennelly KE, Mannix R, Nigrovic LE, et al. Pediatric traumatic brain injury and radiation risks: A clinical decision analysis. J Peds 2013;162:392:397.
30. Lyttle, MD, Crowe L, Oakley E, et al. Comparing CATCH, CHALICE and PECARN clinical decision rules for paediatric head injuries. Emerg Med J 2012;29:785-794.
31. Easter JS, Bakes K, Dhaliwal J, et al. Comparison of PECARN, CATCH, and CHALICE rules for children with minor head injury: A prospective cohort study. Ann Emerg Med 2014;64(2):145-152.
32. Bressan S, Romanato S, Mion T, et al. Implementation of adapted PECARN decision rule for children with minor head injury in the pediatric emergency department. Acad Emerg Med 2012;19(7):801-807.
33. Nigrovic LE, Schunk JE, Foerster A, et al. The effect of observation on cranial computed tomography utilization for children after blunt head trauma. Pediatrics 2011;127:1067.
34. Karpas A, Finkelstein M, Reid S. Which management strategy do parents prefer for their head-injured child? Ped Emerg Care 2013;29(1):30-35.
35. Schonfeld D, Fitz BM, Nigrovic LE. Effect of the duration of emergency department observation on computed tomography use in children with minor blunt head trauma. Ann Emerg Med 2013;62(6):597-603.
36. Xiao B, Wu F, Ma H. Safety and efficacy of symptom-driven CT decision rule in fully conscious paediatric patients with symptoms after mild closed head trauma. Emerg Med J 2013;30;e10; 1-6.
37. Quayle KS. Minor head injury in the pediatric patient. Pediatr Clin North Am 1999;46:2289-2299, vii.
38. Rabiner JE, Friedman LM, Khine H, et al. Accuracy of point-of-care ultrasound for diagnosis of skull fractures in children. Pediatrics 2013;131:e1757.
39. Chung S, Schamban N, Wypij D, et al. Skull radiograph interpretation of children younger than two years: How good are pediatric emergency physicians? Ann Emerg Med 2004;43:718-722.
40. Lloyd DA, Carty H, Patterson M, et al. Predictive value of skull radiography for intracranial injury in children with blunt head injury. Lancet 1997;349:821-824.
41. Riera A, Chen L. Ultrasound evaluation of skull fractures in children. Pediatr Emerg Care 2012;28(5):420-425.
42. Parri N, Crosby BJ, Glass C. Ability of emergency ultrasonography to detect pediatric skull fractures: A prospective, observational study. J Emerg Med 2013;44(1):135-141.
43. Dunning J, Daly JP, Malhotra R, et al. The implications of NICE guidelines on the management of children presenting with head injury. Arch Dis Child 2004;89:763e7.
44. Kochanek PM, Carney, N, Adelson, PD, et al. Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents, second edition. Pediatr Crit Care Med 2012;13:S36-S41.
45. Mellion SA, Bennett KS, Ellsworth GL, et al. High-dose barbiturates for refractory intracranial hypertension in children with severe traumatic brain injury. Pediatr Crit Care Med 2013;14 (3):239-247.
46. Fraser DD, Close TE, Rose KL; Canadian Critical Care Translational Biology Group, et al. Severe traumatic brain injury in children elevates glial fibrillary acidic protein in cerebrospinal fluid and serum. Pediatr Crit Care Med 2011;12(3):319-324.
47. Smith S, Clark M, Nelson J, et al. Emergency department skull trephination for epidural hematoma in patients who are awake but deteriorate rapidly. J Emerg Med 2010;39 (3):377–383.
48. Nelson JA. Local skull trephination before transfer is associated with favorable outcomes in cerebral herniation from epidural hematoma. Acad Emerg Med 2011;18(1):78-85.
49. Patel N, West M, Wurster J, et al. Pediatric traumatic brain injuries treated with decompressive craniectomy. Surg Neurol Int 2013;4:128.
50. Sahuquillo J. Decompressive craniectomy for the treatment of refractory high intracranial pressure in traumatic brain injury. Cochrane Database Syst Rev 2006: CD003983.
51. Honeybul S, Ho KM, Lind CR. What can be learned from the DECRA study. World Neurosurg 2013;79:159-161.
52. Paul SP, Barratt F, Homer S. Treatment and management of head injuries in children. Emergency Nurse 2011;18 (10):23-26.
53. Quality Standards Subcommittee, American Academy of Neurology. Practice Parameter: The Management of Concussion in Sports (summary statement). Neurology 1997;48(3):581-585.
54. Kirkwood M, Yeats, K, Wilson, P. Pediatric sport related concussion: A review of the clinical management of an oft-neglected population. Pediatrics 2006;117:1359-1371.
55. Asplund C, McKeag D, Olsen C. Sport related concussion: Factors associated with prolonged return to play. Clin J Sport Med 2004;14(6):339-343.
56. Ahmed S, Bierley R, Sheikh JI, et al. Posttraumatic amnesia after closed head injury: A review of the literature and some suggestions for further research. Brain Injury 2000;14:765-780.
57. Collins M, Iverson L. On field predictors of neuropsychological and symptom deficit following sports related concussion. Clin J Sport Med 2003;13:222-229.
58. McCrory P, Johnston K, Meeuwisse W. Summary and agreement statement of the 2nd International Conference on Concussion in Sport, Prague 2004. Br J Sports Med 2005;39:196–204.
59. McCrory P, Meeuwisse WH, Aubry M, et al. Consensus statement on concussion in sport: The 4th International Conference on Concussion in Sport, Zurich, 2012. Br J Sports Med 2013;47:250-258.
60. Thomas DG, Apps JN, Hoffman RD, et al. Benefits of strict rest after acute concussion: A randomized controlled trial. Pediatrics 2015;135;213-223.
61. Crowe LM, Catroppa C, Babl FR, et al. Intellectual, behavioral, and social outcomes of accidental traumatic brain injury in early childhood. Pediatrics 2012;129;e262-e268.
62. Anderson V, Godfrey C, Rosenfeld JV, et al. Predictors of cognitive function and recovery 10 years after traumatic brain injury. Pediatrics 2012;129; e254.
63. Wetherington CR, Hooper SR, Keenan HT, et al. Parent ratings of behavioral functioning after traumatic brain injury in very young children. J Pediatr Psychol 2010;35(6):662-671.
64. Blume HK, Vavilala MS, Jaffe KM, et al. Headache after pediatric traumatic brain injury. Pediatrics 2012;129;e31.
65. Alharfi IM, Charyk Stewart T, Foster J, et al. Central diabetes insipidus in pediatric severe TBI. Pediatr Crit Care Med 2013;14(2);203-209.
66. Harper CG, Doyle D, Adams JH, et al. Analysis of abnormalities in pituitary gland in non-missile head injury: Study of 100 consecutive cases. J Clin Pathol 1986;39:769-773.
67. Buzzini SRR, Guskiewicz KM. Sport-related concussion in the young athlete. Curr Opin Pediatr 2006;18:376–382.
68. Jenny C, Hymel KP, Ritzen A, et al. Analysis of missed cases of abusive head trauma. JAMA 1999;281:621-626.
69. Hymel KP, Willson DF, Boos SC, et al. Derivation of a clinical prediction rule for pediatric abusive head trauma. Ped Critical Care Med 2013;14:210-220.
70. Sheets LK, Leach ME, Koszewski IJ, et al. Sentinel injuries in infants evaluated for child physical abuse. Pediatrics 2013;131(4):701-707.
71. Deye KP, Berger RP, Lindberg DM. Occult abusive injuries in infants with apparently isolated skull fractures. J Trauma Acute Care Surg 2013;74:1553-1558.
72. Stewart TC, Alharfi IM, Fraser DD. The role of serious concomitant injuries in the treatment and outcome of pediatric severe traumatic brain injury. J Acute Care Surg 2013;75:836-842.
73. Atabaki S. Prehospital management of traumatic brain injury in children. Clin Ped Emerg Med 2006;7:94-104.
74. Holmes JF, Borgialli DA, Nadel FM, et al; TBI Study Group for the Pediatric Emergency Care Applied Research Network. Do children with blunt head trauma and normal cranial computed tomography scan results require hospitalization for neurologic observation? Ann Emerg Med 2011;58:315-322.
75. Hamilton M, Mrazik M, Johnson DW. Incidence of delayed intracranial hemorrhage in children after uncomplicated minor head injuries. Pediatrics 2010;126:e33-e39.