Special considerations in infants and children

Handbook of Clinical Neurology, Vol. 127 (3rd series) Traumatic Brain Injury, Part I J. Grafman and A.M. Salazar, Editors © 2015 Elsevier B.V. All rights reserved

Chapter 15

Special considerations in infants and children 1

ANN-CHRISTINE DUHAIME1* AND RIMA SESTOKAS RINDLER2 Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA 2

Emory University Hospital, Neurological Surgery, Atlanta, GA, USA

INTRODUCTION Head injury in children is one of the most common causes of death and disability in the US and increasingly, worldwide. In this chapter we will review the epidemiology, injury classification schemes, age-dependent pathophysiology, clinical and imaging assessment tools, general management considerations, specific injury patterns, and outcomes relevant to pediatric patients.

EPIDEMIOLOGY OF PEDIATRIC HEAD INJURY While it is well known that traumatic brain injury (TBI) is the most common cause of injury-related death and disability in children in the developed world, it is also of increasing importance among the leading causes of death in developing countries (Krug et al., 2000; Segui-Gomez, 2003; Babikian and Asarnow, 2009; Centers for Disease Control and Prevention, 2010; World Health Organization, 2010). It is currently the ninth cause of disease burden worldwide, but is expected to rise to third place by 2020 with the projected rise of road traffic accidents in developing countries (World Health Organization, 2010). In the US, there are two large peaks in pediatric head injuries: during early childhood (ages 0–4 years; rate 1337/100 000) and adolescence (ages 15–19 years; rate 896/100 000) (Centers for Disease Control and Prevention, 2010; Faul et al., 2010). Over 600 000 children between ages 0 and 19 years visit the emergency department (ED) for head injury annually, with over 60 000 hospital admissions. Interestingly, the rate of fall-related TBI in 0–14-year-olds seen in the ED between 2002 and 2006 increased by 62%, but hospitalizations

decreased by 30%. This may be due to increased public awareness of the potential adverse consequences of head injury (Faul et al., 2010). Boys with head injuries outnumber girls two to one, and boys aged 0–4 years have the highest combined rates of emergency department visits, hospitalizations, and deaths from head injury of any age group. Approximately 6000 children die annually from head injury in the US (Faul et al., 2010). Mortality rate is highest for adolescents between 15 and 19 years old (19.2/100 000 per year), followed by children under 4 years (5/100 000 per year). Greater than 16 000 children die from all types of injuries, and approximately 80% of all injuries include TBI (Mayer et al., 1980, 1981; Centers for Disease Control and Prevention, 2007). Mortality from TBI of any severity requiring hospitalization is 2.5–4.5% for children versus 10.4% for adults (Alberico et al., 1987; Luerssen et al., 1988; Langlois, 2000). Severe pediatric TBI has a mortality rate that ranges from 16% to over 59% (Mayer et al., 1981; Kraus et al., 1987; Luerssen et al., 1988; Michaud et al., 1992). Additional information regarding epidemiology of adult head injury can be found in Chapter 1. Cause of head injury varies according to age, and reflects developmental abilities and risks associated with each stage of life. Falls account for approximately 50% of head injury in children ages 0–14 years, followed by collision events with a moving or stationary object (24.8%), and motor vehicle accidents (6.8%) (Kraus et al., 1986; Keenan and Bratton, 2006; Faul et al., 2010). The youngest children have the highest rate of fall-related head injuries (Walker et al., 1985; Levin et al., 1992). However, the most common cause of severe TBI and death in this age group is nonaccidental trauma, which accounts for between 24% and 63% of head

*Correspondence to: Ann-Christine Duhaime, MD, Director, Pediatric Neurosurgery, Massachusetts General Hospital, Nicholas T. Zervas Professor of Neurosurgery, Harvard Medical School, 15 Parkman Street, 331 Wang Ambulatory Care Center, Boston, MA 02114, USA. Tel: +1-617-643-9175, E-mail: [email protected]

220 A-C. DUHAIME AND R.S. RINDLER injuries requiring hospitalization (Billmire and Myers, Classification of head injury in adults is further 1985; Duhaime et al., 1992; Keenan et al., 2003). described in Chapter 2 of this book. Motor vehicle accidents and assault occur most often Categorization of injuries by severity, including in adolescents greater than 15 years old (Luerssen et al., “mild,” “moderate,” and “severe” subcategories, is a 1988; Faul et al., 2010). School-aged children are also commonly utilized distinction at all ages, but has limitacommonly injured from sports and recreational activitions because of the similar initial clinical appearance of ties (Luerssen et al., 1988; Mehan et al., 2008). The numwidely differing injury types (Maas et al., 2012). In addiber of sports and recreation-related ED visits for head tion, assessment of injury severity in infants and young injury in this age group increased by 60% in the last children is challenging, and will be discussed in more decade (Gilchrist et al., 2011). Bicycle-related head injudetail in the section on Assessments below. Accurate ries decreased significantly from 1990 to 2005; however, evaluation is further hindered by prehospital treatments despite increasing helmet use, head injury still accounts and interference by pharmacologic agents (Keenan and for over 40% of bike-related deaths (Mehan et al., 2008). Bratton, 2006; Adelson et al., 2012). Additional considAn increasing cause of pediatric mortality is use of allerations in children include a higher incidence of impact terrain vehicles (ATV); fatalities and nonfatal injuries seizures and early seizures, which can cloud clinical increased by 14% and 25%, respectively, in recent years, assessments of injury severity (Yablon, 1993). Finally, despite passage of ATV safety legislation for children parents may have different interpretations of what is a (Carr et al., 2004; Helmkamp et al., 2008). “mild” or “severe” injury, and these terms must be used The financial cost of managing pediatric TBI is trewith caution when communicating with families to avoid mendous. In 2005, over $2.6 billion was spent on hospital confusion. A common example is an isolated skull fraccare for pediatric TBI alone, with an average hospital ture, which many parents would consider a “severe” admission costing over $56 000 (Centers for Disease injury when the word is used in the lay context, but from Control and Prevention, 2012). Annual cost of work lost a Glasgow Coma Scale classification is typically considin this age group was estimated at over $6 billion. The ered “mild” with respect to prognosis for a good neurototal combined cost of care for emergency department logic outcome. The reason this can be important is that visits, hospitalizations, and death from pediatric TBI parents may perceive the physician who describes the was over $3 billion in the US in 2005. Currently, no injury as “mild” as underestimating the seriousness of long-term, prospective population studies have been the event or their degree of concern, a risk when using conducted to determine the number of children left with terms which have both a general usage and a specific permanent disabilities as a result of TBI (Langlois, medical meaning. 2000). One older report estimated that 28 000 children With respect to pathoanatomic classification, chilare left with permanent physical, cognitive, or psychosodren can sustain all types of skull injuries, intracranial cial disabilities annually (Kraus et al., 1990). It was estihematomas, and parenchymal injuries seen in the adult mated that years of potential life lost for children who population (Saatman et al., 2008; Duhaime et al., died from TBI in the US exceeded 420 000 in the year 2012b). In addition, they have some unique injury pat1985 (Kraus et al., 1990). The specific costs of long-term terns that occur exclusively or much more frequently care and follow-up are unknown, but are estimated to be in younger age groups. These are typically seen in the high (Kraus et al., 1990; Langlois, 2000). It is even more context of specific mechanisms occurring during certain difficult to estimate years of lost productivity related to developmental stages in childhood, and include “pingmilder head injuries, which occur in much larger numpong” fractures, diastatic fractures with dural tears, bers, and which may cause more subtle deficits that only crush injuries, cervicomedullary distraction injuries, subbecome evident as children mature and are expected to dural hematomas with hemispheric brain swelling, and perform at a higher capacity. periorbital penetrating injuries. These injury types and associations will be described in more detail below. As in adults, children’s injuries can be classified by INJURY CLASSIFICATION SCHEMES: mechanism, according to the type and magnitude of SPECIAL CONSIDERATIONS IN the causative forces involved, which may include focal CHILDREN impact/contact forces, inertial forces such as translaAs in adults, head injury in children can be categorized tional and rotational acceleration/deceleration, and by injury severity, by pathoanatomic type, and by mechstatic (low velocity) loading forces. However, the anism. In all three of these realms there are several sigresponse to these forces may differ during immaturity nificant differences between adults and children, because of age-dependent differences in morphology particularly at the youngest end of the age spectrum. and tissue mechanical properties, as well as differences

SPECIAL CONSIDERATIONS IN INFANTS AND CHILDREN in injury threshold. A few general differences in the response to these forces based on age-dependent morphology are worth noting. First, the skull in infants and young children is significantly more deformable early in life, which means that impact forces to the head can result in greater deformation of the underlying brain parenchyma. For instance, the skull of a young child subjected to high force impact, such as a fall from a significant height or a motor vehicle crash, may transiently deform inwards, tearing the dura and contusing or lacerating the cortex, leading to both short-term and more long-term consequences. Secondly, because the magnitude of angular acceleration is highly dependent on the mass of the brain, infants and young children experience less angular deceleration than do adults subjected to similar mechanisms of injury. In addition, the consequences of mechanical input may vary with age because of differences in injury threshold for a given degree of tissue deformation, systemic and parenchymal injury response, as well as differences in repair processes. Injury thresholds are difficult to study in human children, but there is some evidence from large animal models that the infant brain may be more resistant to focal deformation, but may be more vulnerable to inertial strains (Raghupathi and Margulies, 2002; Missios et al., 2009). Finally, as an additional consideration regarding injury mechanisms in infants and young children, in some contexts these may be classified as “accidental” and “nonaccidental” with respect to how the injury is thought to have occurred. Specific examples of common pediatric injury mechanisms will be covered in more detail below. The terminology for inflicted injury has evolved over time, as concepts of the mechanisms and pathophysiology have been informed by clinical and research studies. While the term “shaken baby syndrome” is still used by some clinicians, the broader terms “nonaccidental trauma,” “inflicted injury,” and “abusive head trauma” have been endorsed as preferable by a number of authors and organizations because they encompass the wide variety of mechanisms that may occur, and avoid an overly narrow mechanistic definition which can be both controversial and misleading (Christian and Block, 2009).

PATHOPHYSIOLOGIC DIFFERENCES RELEVANT TO INJURY A number of basic physiologic differences occurring during different stages of development influence both susceptibility and response to injury, as well as optimal management.

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Baseline systemic physiologic norms Hemodynamic pressure parameters are lower in children in an age-dependent manner, including central venous pressure. Likewise, heart rate and respiratory rate are higher, while intracranial pressure norms are lower. For this reason, cerebral perfusion pressure (CPP) normal values are smaller in younger patients. While adult goals of CPP of 60–70 are commonly cited, in young children comparable CPP goals may be 40 or 50, although whether treatment aimed at maintaining these values changes outcome remains incompletely studied (Barzilay et al., 1988; Chambers et al., 2001; Figaji et al., 2009; Kapapa et al., 2010; summarized in Kochanek et al., 2012).

Blood volume and shock Infants and young children have markedly smaller blood volumes than do older children and adults (e.g., a newborn’s blood volume is approximately 300 mL, while adults average 5–6 L), which can predispose to shock associated with injuries which would be well tolerated in older patients, such as scalp lacerations, subgaleal hematomas, and long-bone fractures (Nathan and Orkin, 1998). Because of their robust compensatory abilities, the presence of clinical signs of shock indicates that a young patient has decompensated and is in imminent danger; thus, these signs should prompt rapid and appropriately aggressive intervention, beginning with fluid resuscitation.

Brain physiology and age-dependent vulnerability The infant brain has a water content of approximately 90%, compared to adult brain water content of 75%. Myelination increases throughout childhood, particularly steeply in the first several years of life (Brody et al., 1987; Miller et al., 2003), but is not complete until the third to fourth decade of life (Giedd, 2004; Lebel and Beaulieu, 2011). These differences can confound interpretation of imaging findings in infants, sometimes resulting in overly pessimistic assessment of the implication of relative brain hypodensity on CT scan, or misinterpretation of normal structures (falx, transverse sinus, blood vessels) as hemorrhage. Normal cerebral blood flow values are low in newborns (30–45 mL/100 g brain per minute), increase and peak during the first years of life (70 mL/100 g brain per minute), and decrease to adult levels during adolescence (50 mL/100 g brain per minute) (Chiron et al., 1992). This is relevant to the interpretation of clinical research on cerebral blood flow changes after injury, as well as to interpretation of imaging findings. While

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it has been widely stated that children have a higher incidence of brain edema compared to adults, this remains difficult to discern in light of differences in mechanism, injury type, and treatments between ages and over time (Bruce et al., 1981; Aldrich et al., 1992; Lang et al., 1994; Ciurea et al., 2011). Animal studies suggest that brain swelling may vary with specific maturational stage (Duhaime et al., 2003). Patterns of brain swelling associated with specific injuries and management implications will be discussed in more detail below. Neurotransmitter maturation, receptor density and subtype distribution, and other age-dependent changes in intrinsic brain physiology have been hypothesized to contribute to the increased incidence of seizures seen in infants and children associated with traumatic brain injury (Moshe´, 1987; Yablon, 1993; Asikainen et al., 1999; Chiaretti et al., 2000). Many post-traumatic seizures in infants are subclinical or very subtle, leading to a high incidence of under-recognition unless EEG monitoring is obtained (Korff and Nordli, 2005; Bratton et al., 2007). These differences also contribute to a higher rate of failure to control seizures when anticonvulsants commonly used for treatment or prophylaxis in adults are administered (Lewis et al., 1993; Schierhout and Roberts, 2001). A high incidence of impact seizures in milder injuries has also been noted (Yablon, 1993; Chiaretti et al., 2000). Some authors have questioned whether impact seizures represent disinhibition of the cortex rather than true epileptic events, while others suggest true epilepsy-like phenomena (McCrory and Berkovic, 2000; Shaw, 2002). Whether infants and children have increased or decreased susceptibility to more severe consequences of injury at various maturational stages remains an incompletely answered question, and likely depends on which insult of which magnitude during which stage of development. Studies in animals and in premature infants and children have shown different susceptibilities to global hypoxic-ischemic insult, with various cell layers and brain regions showing relative resistance to injury at different ages (Fraser et al., 2007; Yang et al., 2011). Human infants show preferential damage of deep gray matter in both premature and full-term neonates, with premature neonates also showing susceptibility to periventricular white matter damage, and full-term neonates having increased risk for parasagittal watershed territory infarcts (Moorcraft et al., 1991; Huang and Castillo, 2008). Postneonatal hypoxic-ischemic insults result in diffuse gray matter damage, with spared perirolandic structures and structures supplied by the posterior circulation. In older children, deep gray matter nuclei, cortices, hippocampi, and cerebellum are more likely to be damaged by this type of diffuse insult (Huang and Castillo, 2008). Some authors have

extrapolated from relatively poor outcomes in some infant injuries, such as inflicted trauma, to suggest increased vulnerability to mechanical trauma, but this interpretation is complicated by the fact that many of these injuries fall into particular categories and patterns which happen less frequently in older children, so whether the outcomes depend on age or injury type remains unclear (Alberico et al., 1987; Luerssen et al., 1988; Ewing-Cobbs et al., 1998, 1999). In addition, the degree to which such injuries actually represent absolute or relative hypoxic-ischemic insult rather than mechanical trauma per se is incompletely understood (Geddes et al., 2001a, b; Ichord et al., 2007). Researchers utilizing rodent models have commented on potential vulnerabilities due to metabolic changes during maturation (Prins and Hovda, 1998). With respect to mechanical trauma, age-dependent vulnerability may depend on the model used, and thus vary with the pathophysiology of the specific injury type. For example, when scaled for the mass of the brain in large animal models, focal cortical deformational injury (contusion) is associated with a smaller injury in infants compared with adolescents, but inertial injury (axonal strain) demonstrates greater injury in the immature brain (Raghupathi and Margulies, 2002; Missios et al., 2009). How these differences might apply to human children remains incompletely understood.

CLINICAL ASSESSMENT TOOLS FOR INFANTS AND CHILDREN General considerations While there is considerable overlap in standard methods for neurologic examination of patients of different ages, there are special considerations that are helpful in optimizing the examination in infants and children. First, the clinician is more likely to get a representative examination when young children who are alert are observed initially while held on the lap of the parent/caretaker. An overall assessment of mental status can be ascertained even in preverbal children by the level of engagement, interaction, and spontaneous activity. Motor abnormalities and range of motion can be observed during spontaneous play, often easiest in a playroom setting or by observing the child during exploration of the examination room. Children who are sleeping and who can be mobilized often can be brought to alertness most easily by turning on lights, removing blankets and covers, sitting the child up, and providing something to drink; many neurologic functions can thus be tested while observing these behaviors. In contrast, noxious stimulation may cause children to cry or to withdraw, making subsequent examination more difficult. Similarly, in adolescents, noxious stimulation of a sleeping patient

SPECIAL CONSIDERATIONS IN INFANTS AND CHILDREN 223 with neurologic impairment may prompt aggression or both verbal and motor scoring, the latter of which withdrawal and impede further examination. depends on the ability to follow verbal commands. FurSerial examinations are key to detecting changes thermore, young children are unable to reliably localize before serious deterioration has occurred. Changes may a noxious stimulus and do not demonstrate a distinct take the form of decreased frequency, duration, or decortication response until 9–18 months of age, thus complexity of spontaneous verbal or motor activities, preventing accurate motor scoring using the GCS or decreased amplitude or excursion of movements, or any of its commonly used pediatric modifications decreased latency between verbal commands or noxious (Newton, 1998; Kirkham et al., 2008). Seizures are comstimulation and their associated response. In very young mon in infants and young children, and may be subtle, children, increased irritability, increased tone, and arching mimicking spontaneous motor activity. Finally, the may herald incipient deterioration. In some children, GCS is unable to fully assess patients that are sedated, decreased heart rate is the only sign of increasing intracraparalyzed, intubated, or have swollen eyes secondary nial pressure. Of note, these types of subtle changes may to trauma (Newton, 1998). These shortcomings may connot alter the neurologic score, which typically rests on the tribute to an underestimation of injury severity, as well as best a patient can do (detailed below), but will be detected to missed or suboptimally managed injuries in children. by an experienced examiner. Training bedside nurses and For these reasons, numerous pediatric coma scales other front line members of the care team to attend to and have been developed over the last several decades. These communicate these changes is worthwhile, as is simultainclude multiple variations on the adult Glasgow Coma neous examination of the patient by the outgoing and Scale, such as the American College of Surgeons pediatincoming bedside evaluators, to avoid uncertainty about ric GCS (James and Trauner, 1985; American College of whether an examination has changed over time. Surgeons, 1997). Some scales modified or replaced the For children who are more seriously injured, who are GCS verbal and motor subscales to include more ageintubated, or who require sedating analgesics for conrelevant measures, such as crying, consolability, or other comitant injuries, examination can be more challenging. observations such as a “grimace” subscale (Tatman While many approaches are possible, and are outlined in et al., 1997). Others included clinical measures of brainmore detail in the section on this topic below, it has been stem activity such as ocular and oculovestibular our general practice to provide sedation/analgesia using responses (Gordon et al., 1983; Raimondi and continuous low-dose narcotic infusion, most often using Hirschauer, 1984). Despite these modifications, these fentanyl. In most children, this provides adequate analscales continue to present challenges by including gesia and sedation but still enables serial examinations, ambiguous and subjective terms (e.g. “irritable cry,” which can detect changes of the types noted above. In “consolable”), as well as behavioral measures inapplicaaddition, unless there are critical contraindications, such ble to the youngest children (e.g., localization and decoras need for paralytics for effective ventilation, we typitication). Many of these scales have limited interrater cally discontinue all narcotic infusions at 6 hour intervals reliability and few scales have been validated for predicto obtain a nonsedated examination. tive ability in children younger than 2 years (Yager et al., 1990; Holmes, 2005; Kirkham et al., 2008; Fortune and Shann, 2010). In addition, because of the widespread Neuroassessment scales familiarity with the Glasgow Coma Scale in the hospital Numerous pediatric neuroassessment tools have been setting, and assessment of children by subspecialists who developed over the last several decades to aid in examinmay care for both adults and children, scales that have ing children who have sustained traumatic injuries. The scoring ranges or features that are considerably differmost widely used neuroassessment tool for adults and ent from those used in adults may be challenging for verbal children is the Glasgow Coma Scale (GCS), with teams to adopt routinely. its 3–15 total based on eye opening, verbal, and motor The Children’s Hospital of Philadelphia Infant Coma scores. However, the GCS is problematic for use in Scale (also known as the “Infant Face Scale,” or IFS) was infants and young children because it utilizes some meadesigned as an attempt to overcome some of these obstasures that fail to take normal developmental changes into cles in infants and young children with traumatic brain account (Simpson and Reilly, 1982; Raimondi and injuries (Durham et al., 2000). In parallel with the Hirschauer, 1984). Cortical activity may be reflected by GCS, the IFS is a 15 point scale composed of “eye,” different behavioral repertoires early in life; young chil“motor,” and “verbal/face” measures, with lower scores dren are preverbal, and are often frightened and unable indicating more severe neurologic dysfunction. In place to cooperate in the hospital setting even when they have of the verbal score, the IFS assesses a child’s responsive developed some language skills (Tatman et al., 1997; facial expression and crying behavior, which reflects corKirkham et al., 2008). These circumstances confound tical function. The motor scale reflects age-related and

224 A-C. DUHAIME AND R.S. RINDLER trauma-associated motor behavior, including a category history and physical examination findings to identify for “seizure-like activity” for patients demonstrating low risk patients and guide imaging (Kuppermann rhythmic spontaneous movements, which typically indiet al., 2009; Goldberg et al., 2011). In general, these cate a more serious injury in infants and young children. approaches have suggested that CT imaging is not indiHowever, while the IFS has been demonstrated to have cated in children < 2 years if the child demonstrates a norimproved interrater reliability compared to the pediatric mal mental status, no parietal, occipital or temporal scalp GCS, there remains no single, gold standard neuroashematoma, no loss of consciousness, no evidence of sessment tool that has been adequately validated to skull fracture, normal behavior as described by caretaker, reflect injury severity and to predict outcome for the and has no high-risk mechanism of injury (Kuppermann youngest patients. et al., 2009). Some of these concerns have been obviated by increasing utilization of MRI for trauma screening and follow-up, as described in more detail below. IMAGING CONSIDERATIONS IN In addition to trauma screening for initial triage, CT PEDIATRIC TRAUMATIC BRAIN INJURY remains the modality of choice for detailed imaging of Since the 1970s, computerized tomography (CT) scanthe bony anatomy. Therefore, for penetrating injuries, ning has been used as the primary screening tool for identification of skull or facial fractures (often relevant detection of intracranial lesions after traumatic brain in the evaluation of possible child abuse), and odontoid injury. More than 2.7 million children undergo CT scans or other spine fractures, CT scans remain the modality in the US each year, including many children with head most often utilized. Finally, CT angiography may be utitrauma whose injuries appear clinically mild, but who lized to assess vascular injuries, most often screening for may still harbor a progressive lesion. There has been arterial dissection (discussed in more detail below). increasing recognition that the amount of ionizing radiHowever, this involves a significant volume of contrast ation involved in these studies is significant and potenthat must be instilled rapidly, creating limitations in tially deleterious to infants and children, being linked younger children with smaller caliber intravenous lines to increased cancer risk as well as long-term cognitive (Atkinson, 2006). effects (Brenner et al., 2001; Hall, 2002; Hall et al., The development of MRI techniques using short 2004). Besides the concern about radiation exposure, acquisition times as well as “moving target” software the degree to which CT scans are degraded by motion to correct for patient motion now make MRI a feasible makes sedation in children a frequent necessity, engenalternative for trauma screening for brain as well as dering additional time, risk, and expense (Jevtovicspine imaging (Forbes et al., 2001; Missios et al., Todorovic et al., 2003; Zou et al., 2011). For these 2008). Specific protocols that limit sequences to those reasons, the use of alternative technologies for detection needed to make surgical and general management deciof traumatic intracranial lesions is a desirable goal. One sions may be utilized, although sensitivity and specificity approach has been to reduce the dose given to children for acute injury screening compared to standard or undergoing CT scans, a strategy in use in many trauma reduced-dose CT protocols are still under study centers (Frush, 2002; Goske et al., 2010). Another (Kochanek et al., 2012). approach has been to use decision rules to determine In the subacute and chronic phase of injury, MRI which children fit a pattern of injury for which a CT scan offers useful insights into a number of pathophysiologic has a reasonable yield in detecting clinically significant processes that may be used to guide both management lesions (Goldberg et al., 2011). and prognostic prediction. Diffusion-weighted imaging While most centers continue to use CT scans for chilcan define areas of ischemia before CT scan, and dren with more significant head injuries or multisystem blood-sensitive or edema-sensitive sequences such as trauma, guidelines for the use of CT scan for screening T2 and susceptibility-weighted imaging can provide children with milder injuries continue to be developed detail about contusion evolution and associated mass and refined. The incidence of intracranial findings in effect as well as traumatic axonal injury. Diffusion tenasymptomatic, mild TBI in children is between 3% and sor and diffusion spectrum imaging provide details 7% (Quayle et al., 1997; Gruskin and Schutzman, about cellular and even subcellular disorganization, 1999). The percentage of children with mild TBI requirand spectroscopy reflects metabolic changes. Various ing surgical intervention is very low (0.1–0.6%) (Schunk types of connectivity maps and functional paradigms et al., 1996). However, prospective cohort studies have interrogate brain function, plasticity, and repair shown that between 35% and 53% of children with mild (Hunter et al., 2012). MR angiography and venography TBI undergo CT head imaging (Kuppermann et al., as well as perfusion techniques can provide detailed 2009). This is likely due to an effort to not miss signiinformation about vascular structures and blood supply, ficant but rare intracranial pathology. Thus, some instiand MRI of the spine assesses both ligamentous and tutions have implemented prediction rules based on parenchymal damage.

SPECIAL CONSIDERATIONS IN INFANTS AND CHILDREN Several other imaging modalities are used clinically or experimentally in traumatic brain injury in children. Ultrasound can be used in infants to follow hemorrhages and ventricular size, most often in relation to birth trauma (Ment et al., 2002; Leijser et al., 2006). Nearinfrared spectroscopy, transcranial Doppler, and other bedside imaging modalities have been used for real-time, portable brain interrogation (Byrd and Seibert, 1999; Koch and Kernie, 2011). Radioisotope brain scans have great utility as an adjunct to the determination of brain death, discussed in more detail below (Nakagawa et al., 2012). Additional details on the different neuroimaging modalities can be found in Chapters 17–19 of this book.

MANAGEMENT OF PEDIATRIC HEAD INJURY: GENERAL PRINCIPLES While major technical advances in imaging and monitoring provide new tools to refine understanding of injury evolution, the foundation of head injury management continues to rest first and foremost on clinical evaluation. Recognition of patterns of injury based on the history and presentation, knowledge of potential pathways of pathophysiologic progression, and awareness of subtle early signs of deterioration help the treating team avoid preventable deleterious secondary events and thus optimize outcome.

Initial triage and management of pediatric head injury To inform initial triage and management of traumatic brain injury, and to facilitate communication and planning among different specialties caring for injured children, the authors utilize a structured basic data set of specific elements from the history, physical examination, and imaging findings. Injuries are categorized in an algorithm designed to prevent specific types of complications, and to match the tools needed to monitor these changes with the specific clinical injury pattern. This approach was designed to be applicable to all ages of patients, and is presented here in the pediatric context (Table 15.1, Fig. 15.1). The scheme helps divide injuries into “swelling prone” and “nonswelling prone” categories, based on their overall propensity to be associated with dangerous tissue shifts associated with deterioration. These principles are consistent with international efforts to classify and manage patients along multimodality schemes rather than just utilizing severity of injury to guide therapy (Saatman et al., 2008; Whyte et al., 2010; Maas et al., 2012).

Basic minimum acute data This data set includes information about the history of the injury most often provided by family or by emergency medical personnel, including time of injury,

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mechanism details, best examination at the scene, as well as information about physiologic factors that might exacerbate the primary injury, such as apnea or shock. Included in this checklist are features of the history that are basic but can be missed if information is not gathered from those who were present at the scene, especially when patients are treated in the pre-hospital setting with sedation and/or paralytic agents. Specific data include whether the patient had a clear history or physical evidence suggestive of an impact to the head, whether the examination was symmetric or asymmetric, and whether the patient was clearly seen to move the legs. The initial physical examination at the hospital is performed via standardized age-appropriate tools, as detailed in the Assessment section above. It is also very helpful early in the patient’s course to obtain an actual or estimated weight, for subsequent use in fluid and medication administration. The third component of the evaluation of most neurosurgical patients is imaging; at a referral center, many patients will arrive with imaging done at an outside facility. It is essential to know the interval between the injury and the imaging, as this will help determine how likely further deterioration might be and whether follow-up imaging will be needed. From these data, the first major question to be addressed by the surgeon is whether there is a mass lesion requiring immediate intervention, that is, one causing neurologic symptoms or significant tissue shifts, either at the present time or with predictable worsening during the acute phase of management. To help predict the latter possibility, the information from the various sources of data is used to categorize two broad injury patterns, as described below.

Swelling-prone and nonswelling-prone injuries Injuries in the “swelling-prone” category (Table 15.1) include those in which parenchymal response to injury is often associated with a significant risk of dangerous tissue shifts and herniation syndromes, due to the nature of the injury and its location. These include acute subdural hematoma in a normal (i.e., nonatrophic) brain; multifocal large contusions; temporal or posterior fossa lesions; high energy contact injury; gunshot wounds; or any injury exacerbated by hypoxic-ischemic injury. Patients with injuries that generally have lower risks of catastrophic tissue shifts include diffuse axonal injury; isolated focal lesions distant from herniation sites such as the brainstem or falx; chronic subdural hematomas; and lesions in patients with pre-existing tissue loss such as diffuse brain atrophy or encephalomalacia. While there are exceptions to these general categories, and while there are some inclusions that are not strictly related to brain swelling per se but may have similar

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Table 15.1 Head injury: initial assessment and management for neurosurgical consultants Head Injury: Initial Assessment and Management for Neurosurgical Consultants I. Basic minimum acute data History - Time of injury - Mechanism - Kinematics; energy, speed, height - Struck head? - Best exam at scene - Loss of/level of consciousness - GCS - Asymmetry (pupils, motor) - Moved legs? - Exacerbators - Apnea - Shock - Prolonged extraction - Other injuries - Resuscitation Exam - Via standardized tool (GCS, motor, pupils, other) Imaging - Time of imaging - Is there a mass lesion causing symptoms or significant tissue shift now or with predictable worsening?

Swelling-prone injuries

Non-swelling-prone injuries

Acute subdural hematoma (not in atrophic brain) Multifocal/large contusions Temporal or posterior fossa lesions High energy contact injury Gunshot wound + Exacerbators

“Pure” diffuse axonal injury Isolated focal lesion not near brainstem, falx Chronic subdural hematoma Atrophic/encephalomalacic brain

GCS, Glasgow Coma Scale.

consequences to adjacent important structures, they remain a starting point for strategies to tailor intervention to typically associated risks. Specific interventions will be described in more detail below.

ACUTE PHASE MANAGEMENT OF PEDIATRIC HEAD INJURY Evidence-based guidelines documents for pediatric head injury The idea that treatments should reflect an objective review of scientific evidence has been a central concept in all areas of care for several decades, and this includes management of traumatic brain injury. In the mid-1990s

a group of clinicians, mostly neurosurgeons, reviewed a large portion of the available literature and published “Guidelines for the Management of Severe Head Injury in Adults” (American Association of Neurological Surgeons, 1996). In 1997, a similar group of pediatric neurosurgeons and representatives from related fields attempted a similar effort reviewing literature specific for children, but so few data on children were available that the effort did not result in a publication (Luerssen, 1997). In 2003 another group again attempted a literature review on pediatric head injury, and this did result in a publication, although as in the prior effort, it was acknowledged that significantly more data would need to be obtained before firm recommendations could be

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Initial management algorithm, head injury

Is there a mass lesion causing symptoms or significant tissue shift now or with predictable worsening? yes

no

OR

Is there a swelling-prone injury (see Table 15.1) with significant risk of increased ICP or dangerous tissue shift during the acute course? no (see Table 15.1)

yes

Can patient be examined reliably, serially? (follows commands, localizes) yes

Consider decompressive craniotomy and/or ventriculostomy; ICP monitor

no

Follow

ICP monitor

Lesion type with significant potential for progression without clinical correlate** Exam or symptoms worsening/failing to improve? Focal

Non-focal

Imaging

Check Na, EEG, imaging

** Unoperated epidural hematoma, significant contusion, others at discretion of treating physician

Fig. 15.1. Initial management algorithm for head injury.

made about most clinical questions (Kochanek, 2003). In 2012 an update on acute medical management of severe traumatic brain injury in infants, children, and adolescents was published, and this included some additional evidence, although for many common management decisions there remain scant data on which to base firm conclusions as to an optimal approach (Kochanek et al., 2012). In this updated version, the authors did not suggest a particular order of therapies or intensity escalation as was present in the earlier version of the document, as there is little information on optimal combinations of treatments for specific injury types or injury evolution. In addition, some treatments are utilized at different times, depending on the needs at hand; for example, hyperosmolar therapy may be used during resuscitation and again later in the course; similarly, paralytics may be needed in some children, most often those with extracranial injuries, but are never needed in many children. Thus, understandably, there are differences in management schemes depending on patient specifics and on and personal preferences among centers and individual practitioners. The evidence reviews cited above play an important and useful reference role in capturing the state of evidence at the particular time of its writing.

We will briefly outline some of the practical points regarding medical and surgical management specific for pediatric patients.

Evacuation of mass lesions, surgical decompression, and cerebrospinal fluid drainage The main indication for consideration of early surgery is the presence of a mass lesion requiring immediate intervention, that is, one causing neurologic symptoms or significant tissue shifts, either at the present time or with predictable worsening during the acute phase of management (Table 15.1). Following the algorithm in Fig. 15.1, a second indication for consideration of surgery is the presence of a swelling-prone injury, as described in Table 15.1, which the surgeon considers to carry significant risk of increased intracranial pressure (ICP) or dangerous tissue shift during the acute course. Thus a small subdural with significant associated mass effect or brain swelling, a significant contusion in the posterior temporal region or posterior fossa, or a high energy contact injury with multifocal contusions that can be predicted to swell over time all might prompt consideration for

228 A-C. DUHAIME AND R.S. RINDLER decompression. On the other hand, contusions far from Seizure prophylaxis sites of herniation or in atrophic brain are less likely to There are few data specific for children with traumatic be associated with dangerous tissue shift. A number of brain injury, so extrapolating from adult data, pediatric relatively small series and meta-analyses have been perclinicians may use prophylaxis during the first week formed regarding decompressive craniectomy in children, after injury in those children in whom a high incidence as well as one randomized trial in which bilateral temporal of seizures is known to occur and in those in whom a decompressions without dural opening were done for seizure would complicate management or increase refractory ICP (Taylor et al., 2001; Guresir et al., 2012; morbidity (Bratton et al., 2007). The benefit of seizure Weintraub et al., 2012). As with other treatments, there prophylaxis has been difficult to prove in children, in are differences among centers with respect to indications part because of the complex pharmacologic manageand timing of surgery as well as surgical technique, with ment and heterogeneity of pediatric head injury trials most series describing large cranial and dural openings. In (Young et al., 2004). Thus for each patient, the risk aggregate, these studies appear to demonstrate efficacy of side-effects from antiepileptic medications is of decompression for decreasing intracranial pressure, weighed against the risk of seizures in the early postinand some evidence of improved outcome, especially when jury period. Children with cortical contusions, brain lacsurgery is performed early for focal rather than diffuse erations, subdural and subarachnoid hemorrhage, and pathology. Significant complications and need for addiintraparenchymal hemorrhages are considered higher tional interventions are also noted in most series, includrisk for early seizures, as are infants with subdural ing an increased risk of post-traumatic hydrocephalus and hematomas and other injury types. Infants have a high late wound complications including infection and bone incidence of subclinical seizures and may require conresorption (Kan et al., 2006; Adamo et al., 2009; Suarez tinuous EEG monitoring to determine that seizures are et al., 2011). Optimal timing of cranioplasty remains conoccurring (Barlow et al., 2000; Chiaretti et al., 2000; troversial, though there is some evidence to suggest early Liesemer et al., 2011). Because of the associated bone replacement maybe associated with decreased comincrease in cerebral blood flow with seizures, children plication rates, particularly in children (Chang et al., 2010). with early tissue shifts near the brainstem, such as One unique feature in pediatric traumatic brain injury patients with mid- or posterior temporal contusions, is the use of decompressive craniectomy in the setting of may deteriorate precipitously in the setting of a clinical inflicted injury; one series showed outcomes in this setseizure; therefore, careful prophylaxis in such patients ting were worse than in children with accidental mechashould be considered. nisms, likely reflecting an increased severity of injury in The agent of choice for post-traumatic seizure prothis setting (Oluigbo et al., 2012). This injury type will be phylaxis may vary with age, but because of a favorable discussed in more detail below. risk profile and simpler pharmacokinetics compared to Cerebrospinal fluid drainage, usually via ventriculostother antiepileptic drugs, many centers use levetiraceomy, is another widely used method to decrease intracratam as the agent of choice in children. For infants, nial pressure, although its effects have not been studied choice of agents varies among centers and practiin a strict comparative fashion to other means of intracrationers, weighing in maturational changes in receptor nial pressure management in adults or in children. Aneccharacteristics that may make some newer agents more dotally, many surgeons have come to use this treatment effective. as the next step after hyperosmolar therapy for patients Children have a significant risk of impact seizures with swelling-prone injuries. The surgeon may choose to with concussive-type head injury; these do not appear place a drain at the time of evacuation of a mass lesion or to predict an increased risk of long-term seizures, and at the time of decompressive craniectomy; intraoperative some workers hypothesize that these are not “true” seiultrasound may be helpful in facilitating placement zures but rather reflect transient functional decerebraunder these circumstances. Alternatively, ventriculostion (Hahn et al., 1988; McCrory and Berkovic, 2000; tomies can be placed at the bedside in patients who have Perron et al., 2001). Prophylaxis may decrease the risk injuries in which drainage is thought likely to help prevent of recurrent early seizures (those occurring within the dangerous increases in pressure. Lumbar drainage in first week), but has not been demonstrated to alter the addition to ventricular drainage has been reported, but incidence of late seizures in adults (Temkin et al., to date has not been used widely (Levy et al., 1995). There 1990). Children who have early seizures in the setting are few data to suggest an optimal method for weaning of risk factors for prolonged seizures, such as contupatients from ventricular drainage, and in some situasions or other parenchymal lesions, may benefit from tions, such as large subgaleal CSF collections associated consultation by a child neurologist who can follow the with hemicraniectomy, conversion to an indwelling shunt outpatient course. Often clinical as well as EEG criteria may be chosen to facilitate mobilization, wound healing, are used to help decide duration of treatment. and rehabilitation.

SPECIAL CONSIDERATIONS IN INFANTS AND CHILDREN

Intracranial pressure monitoring Despite widespread use of intracranial pressure monitoring in the US for patients with the more severe forms of traumatic brain injury characterized by unconsciousness, a recent evidentiary review of the pediatric literature was unable to clearly confirm a positive effect on outcome in published series (Kochanek et al., 2012). In the adult head-injured population, treatment based on intracranial pressure monitoring did not lead to better outcomes than did protocol-based treatment using serial clinical examination and imaging (Chesnut et al., 2012). It seems likely that the addition of age-dependent factors to the heterogeneity inherent in traumatic brain injury would likely make the task of finding evidence that monitoring improves outcomes across the spectrum of injury in children even more difficult. Larger collections of data which enable stratification across injury types and host factors hold promise of being able to demonstrate for which subset of patients and under which circumstances monitoring is likely to provide benefit (Saatman et al., 2008). At present, it would seem prudent to consider ICP monitoring in any patient in whom assistance with following the emerging pathophysiology of brain swelling or detecting delayed mass lesions would be helpful, especially in patients for whom frequent serial examinations or repeated imaging are not feasible or practical. Clear data on the exact role of specific thresholds of ICP or perfusion pressure in children remain elusive (Kochanek et al., 2012). With respect to monitoring technology in children, the same methods available for adults are those most widely used (fiberoptic, strain gauge, or fluid-coupled transducers). Noninvasive monitoring has been attempted by numerous groups, including a variety of technologies, but to date none has garnered widespread acceptance (Wiegand and Richards, 2007).

Osmotherapy The use of hypertonic saline for resuscitation and for treatment of intracranial pressure via a euvolemic dehydration strategy has been studied in adults by many authors, and in children by a number of groups, generally with positive results reported. This has led to a trend for less use of mannitol and more use of hypertonic saline in children with traumatic brain injury (Simma et al., 1998; Khanna et al., 2000; Sakellaridis et al., 2010; Bennett et al., 2012). Hypertonic saline has the advantages of not decreasing intravascular volume with resultant hypotension, and also a higher serum osmolarity can be tolerated compared to using mannitol, because it is associated with less renal damage. Concentrations and dosing schedule vary in different reports, but 3% saline in a continuous infusion, often after an initial

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bolus, is a common strategy (Luu et al., 2011; Kochanek et al., 2012). Hypertonic saline does have risks, including renal toxicity and cental pontine myelinolysis thought to be due to rapid shifts in osmolarity. For this reason, the lowest dose that accomplishes the goal of intracranial pressure control or decreased brain swelling as judged by clinical examination or imaging is advised. This strategy also allows “room to go” if swelling increases over time.

Analgesia, sedation, and pharmacologic paralysis There are few data specifically for children to guide the clinician in this area, except for the contraindication for prolonged use of propofol as noted by the US Food and Drug Administration related to the so-called “propofol syndrome” in children (Wooltorton, 2002; Kochanek et al., 2012). Various centers use different sedating and analgesic agents as intermittent or continuous infusions, often including narcotic analgesics and benzodiazepines (Jenkins et al., 2007). It has been the authors’ practice to use a continuous infusion of fentanyl as a single agent as an initial approach, at the lowest dose needed for appropriate analgesia for noxious stimulation associated with intubation and other interventions, as well as pain associated with the injury itself. In most instances, this dose will also allow for serial neurologic examinations, and at a steady state, allows the bedside team to detect changes over time. The narcotic is also fully and rapidly reversible if questions arise about changes in the neurologic examination. In the authors’ experience, midazolam can be added for additional sedation, either intermittently or as an infusion, but can alter the examination in a less predictable manner, making changes somewhat more difficult to detect. In addition, some children have paradoxical or other unpredictable reactions to various sedatives that may cloud clinical assessment (Desai et al., 2010). Dexmedetomidine, a newer a-2 selective agonist with similarities to clonidine, has the advantage of being able to provide sedation with less respiratory depression than narcotics or benzodiazepines. It has been used successfully in pediatric intensive care units as a primary sedative agent or as a bridge to extubation in ventilated children. While most published series of use of dexmedetomidine in pediatric intensive care unit settings have excluded patients with neurologic dysfunction, the agent has been used for surgical sedation and awake craniotomies in children, and is gaining more widespread use in the PICU setting (Carollo et al., 2008; Czaja and Zimmerman, 2009). Paralytic agents are also used by various centers for differing indications; in the authors’ center, they are used rarely, mainly to manage intracranial hypertension

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in the context of potentially dangerous tissue shifts in cases in which pressure elevation appears to be specifically related to motor activity such as posturing. Other instances include multitrauma or critical pulmonary illness in which ventilatory control is facilitated by muscle relaxation. In patients with head injury in whom sedation and muscle paralysis must be utilized for other reasons, ICP monitoring must be strongly considered, as well as regular intermittent weaning of medication for clinical examination whenever possible; these measures help guard against unrecognized deterioration. For children who have pain related to injury who do not need narcotic administration or other major sedative, nonsteroidal analgesics and acetaminophen (paracetamol) are the mainstay of pain management. While the former have a theoretical risk of increasing bleeding risk, they have been used successfully for postcraniotomy pain management in children without an apparent increase in bleeding risk (Bauer et al., 2010).

Additional treatment methods Hypothermia has been shown to be protective for neonatal hypoxic-ischemic insult and adult cardiac arrest (Doherty et al., 2009; Arrich et al., 2012; Shankaran et al., 2012). In adult as well as pediatric traumatic brain injury, discerning an overall protective effect has been more difficult, in part because of its association with increased risk in trials of traumatized patients (Clifton et al., 2001; Adelson et al., 2005; Hutchison et al., 2008; Kochanek et al., 2012; Mancera and DeCou, 2012). Thus, at present, use of therapeutic hypothermia in traumatic brain injury has not been widely adopted, though avoidance of hyperthermia is recommended. Barbiturates have been used for decades for treatment of severe traumatic brain injury in adults and children, usually as a “late tier” therapy, and/or in combination with other interventions (Eisenberg et al., 1988; Glick et al., 2011). There are few data available to guide the clinician in the use of barbiturates in children, and it is generally considered at the option level in selected cases (Kochanek et al., 2012).

SPECIFIC INJURY PATTERNS IN CHILDREN “Ping-pong” fractures Smoothly indented “ping-pong” skull fractures occur most often in infants and young children from contact mechanisms. They occasionally occur before birth due to contact of the fetal head with bony prominences, and also can be seen in association with labor and delivery. In infancy they occur from low-height falls, and once children become ambulatory, are most often

associated with falls from standing height against a firm pointed surface, such as the corner of a low table. They are rarely, if ever, associated with underlying brain injury. Ping-pong fractures can be treated conservatively and allowed to remodel, or can be treated with vacuum application, or by burr hole surgery through which the indented bone is elevated with an instrument (Tan, 1974; Steinbok et al., 1987).

“Growing” skull fractures These enlarging, pulsatile bone defects occur in association with diastatic linear skull fractures with underlying dural tears. They are found most often in children whose injury occurs within the first few years of life, typically from a high-force contact mechanism such as a fall from a significant height or a motor vehicle crash. Diagnosis may be delayed for several years, when the pulsatile defect and underlying encephalomalacic “leptomeningeal cyst” is confirmed by examination and radiologic findings. The development of a growing skull fracture can be predicted acutely by the findings of a diastatic fracture with underlying contusion and dural tear on MRI (Husson et al., 1996). Early repair may prevent progressive erosion of the fracture edges and extensive retraction of the dural edges.

Crush injuries These occur from static (slow) loading conditions, most often when young children pull heavy objects onto their heads, or when they are struck and run over by a vehicle, usually backing out of a driveway (Duhaime et al., 1995; Gonzalez Tortosa et al., 2004). Multiple basilar and calvarial skull fractures can occur in association with crush injuries, and despite a remarkable ability of even an immature skull to withstand this type of force, variable neurologic consequences can ensue if the brain experiences deformation from forces resulting in skull failure. Death may occur from concomitant distraction injuries to the upper cervical spinal cord.

Subdural hematomas in infants and young children These can occur from accidental, or, more often, nonaccidental trauma. A complete discussion of this topic is outside the scope of this chapter, but in general, subdural hematoma in young children can be associated with a spectrum of neurologic findings, and can present with minimal signs and symptoms all the way to coma and death (Chiesa and Duhaime, 2009; Christian and Block, 2009). A subset of infants and toddler-aged children will demonstrate associated patchy hypodensity and some will show widespread cortical damage in one

SPECIAL CONSIDERATIONS IN INFANTS AND CHILDREN

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Fig. 15.2. Two-year-old child with inflicted injury. (A) Acute computed tomography (CT) scan showing thin but extensive right subdural hematoma (arrow) and midline shift. (B) Magnetic resonance imaging (MRI) 1 week after hemicraniectomy performed on day of admission, showing marked right brain swelling. (C) CT scan 2 weeks after injury, showing reduction in right brain swelling, and preservation of left hemisphere. The right hemisphere went on to marked atrophy, and the child was ambulatory with a left hemiparesis and mild to moderate cognitive impairment.

or both hemispheres, the so-called “big black brain” (Dias et al., 1998; Duhaime and Durham, 2007). This typically results in whole-hemispheric brain swelling and, ultimately, profound atrophy in survivors. Children with the unilateral form of severe brain injury and swelling may be treated with hemicraniectomy, which may prevent secondary infarction of the contralateral frontal lobe due to subfalcine herniation and frontal compartment syndrome (Figaji et al., 2006; Adamo et al.,

2009; Oluigbo et al., 2012) (Fig. 15.2). Children with the bilateral form of hemispheric hypodensity have poor outcomes regardless of intervention (Duhaime et al., 1996; Graupman and Winston, 2006).

Cervicomedullary distraction injuries Infants and young children have relative vulnerability for injury in the upper cervical spine, most often

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Fig. 15.3. Cervical distraction injuries. (A) Lateral cervical plain film in 10-month-old child in car seat who was in a high speed car crash, showing space between occiput and C1, and between C1 and C2 (arrows). Extensive basilar subarachnoid hemorrhage could be seen on computed tomography (CT) scan. (B) CT scout view, 3-year-old child in car seat during high speed crash, showing suggestion of increased distance between occiput and C1 (arrow). (C) Hemorrhage can be seen in retroclival space and in the anterior subarachnoid space at C1–2 on axial noncontrast CT scan.

ligamentous rather than bony in nature (Kriss and Kriss, 1996; Pang, 2004). One setting in which this may be seen is high-speed motor vehicle crashes in which the child is restrained in an infant seat with a harness, in which the only major motion possible is distraction of the cervical spine. This can lead to high cervical cord injury, but in some instances children will present relatively intact but with an unstable spine, which can be overlooked if findings are not recognized. These can include subarachnoid or extra-axial hemorrhage at the cervicomedullary junction, retroclival hemorrhage, and widened

interspinous distances on plain cervical films or the lateral scout film of a CT scan (Fig. 15.3). Placing a young child into a too-large cervical collar can exacerbate this injury, and sandbags with tape are a safer method of immobilizing the spine if a proper sized collar is not immediately available. MRI is the test of choice for defining this type of injury. Treatment is variable, and depends on the specifics of the injury and the age of the child. Some children can be treated with prolonged cervical immobilization and eventually heal without surgery.

SPECIAL CONSIDERATIONS IN INFANTS AND CHILDREN

Skull penetration injuries Because of the thin skull of infants and young children, penetrating injuries can occur with relative ease, especially around the face and orbits. Sometimes penetration has occurred with no recognition by caretakers. The injury may come to light when bleeding or a CSF leak is noted, or when delayed infection occurs. Special radiographic techniques can be helpful to discern penetrating objects, such as plant matter (e.g., pencils or sticks), which may contain air.

Arterial dissections Presumably because of flexibility of the spine, children may present with dissections after relatively minor trauma. The diagnosis may be made when transient ischemia or infarction occurs in a delayed fashion after a relatively minor injury. A high level of suspicion must be maintained for dissection in any child or adolescent with delayed onset of new neurologic symptoms (Kim et al., 1997).

Concussion A full discussion of head injury at the milder end of the severity spectrum in children is beyond the scope of this chapter, but a few comments on concussion in children are warranted. The term “concussion” has had different meanings over time and in various contexts, and has been used by different specialties to describe a variety of clinical entities. For this reason, the authors have proposed the term “concussion spectrum” to designate the variety of signs, symptoms, and consequences falling under this general heading (Duhaime et al., 2012a). At present, the exact structural and physiologic correlates of various subtypes of symptom clusters, the short, intermediate, and long-term consequences, and the various host and injury risk factors that determine these outcomes in children remain incompletely understood. Management has focused on symptom alleviation, and on decreasing the risk of more serious consequences including the rare but potentially devastating situation known as “second impact syndrome” (Saunders and Harbaugh, 1984). This latter appears most often to occur in the setting of acute subdural hematoma with headache, which is exacerbated by a second impact event. Whether children as a group are more susceptible to the effects of single and/or repeated head impact remains incompletely understood. This is an area of intense interest and it is likely that more data will lead to refinement in classification, risk stratification, understanding of pathophysiologic mechanisms, symptom treatment, and prevention efforts in the coming years.

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PROFOUND INJURIES AND BRAIN DEATH IN CHILDREN A number of professional organizations have created guidelines for the determination of brain death in children (Task Force on Brain Death in Children, 1987; Nakawara et al., 2012). Most of these have depended largely on serial clinical examinations, with adjuvant methods including EEG, angiography and nuclear flow studies. Other confirmatory tests have been suggested but not fully validated, including MRI, transcranial Doppler, CT angiography, and brain tissue oxygenation, having been reported in a mixture of adult and pediatric settings (Zurynski et al., 1991; Aichner et al., 1992; Frampas et al., 2009; Figaji and Kent, 2010). The treating physician is often called upon to meet with the family of a child when a devastating but potentially survivable injury has occurred, or when brain death has been diagnosed or is felt likely to be imminent. It goes without saying that the way in which this information is communicated has a profound influence on how the entire experience is perceived, and has long-lasting effects on how a family is able to cope with what for many is the worst event imaginable. This interaction is often most challenging when a child has minimal residual function but does not meet brain death criteria, and when decisions still must be made regarding level of intervention. The senior author has found it helpful in this situation to review options with wording along the following lines: “Some families in this situation choose [path A], and others feel the best thing to do is to choose [path B].” This “third party” approach can help caretakers grasp that decisions can vary among families and that different options are available and equally legitimate.

OUTCOMES AND REHABILITATION While outcomes are difficult to predict in TBI overall because of the heterogeneity of injury type, severity, mechanism, secondary insults, and patient factors, the effects of age have been the focus of several studies (Walker et al., 1984, 1985). Overall, given a similar injury severity and type, most reports suggest that children have a better prognosis than do adults, with lower likelihood of persistent vegetative state or death (Alberico et al., 1987; Costeff et al., 1990; Mushkudiani et al., 2008). However, data can be found that younger children have both worse and better outcomes, depending on the specific age and case mix, with series having more inflicted injuries showing worse outcomes in younger children (Sarsfield, 1974; Mahoney et al., 1983; Alberico et al., 1987; Luerssen et al., 1988; Levin et al., 1992; Duhaime et al., 1993; Duhaime et al., 1996). Sorting out the effects of age as an independent variable maybe

234 A-C. DUHAIME AND R.S. RINDLER facilitated by ongoing efforts to enter children into large Although children have lower mortality from TBI, databases which may allow for stratification and suffimany of those who survive will demonstrate long-term cient numbers of patients to analyze different prognosdisabilities (Kraus et al., 1987; Luerssen et al., 1988; tic variables (Maas et al., 2007; Miller et al., 2012). Costeff et al., 1990). Studies examining health-related General factors that predict worse outcome among quality of life have shown that all severities of TBI children include age under 4 years or adolescence (likely can decrease these measures (Rivara et al., 2011). Cognirelated mostly to mechanisms of injury in these ages), tion and communication may be impaired, especially in low Glasgow Coma Scale score, long post-traumatic children who are comatose or obtunded on admission amnesia, prolonged coma, and secondary insults includ(Rivara et al., 1994; Yeates et al., 2001; Ewing-Cobbs ing hypotension, hypoxia, and hypothermia (Office for and Barnes, 2002; Levin et al., 2008). Children with National Statistics 2002; Office for National Statistics, TBI may have lower social well-being with difficulties 2004; McHugh et al., 2007). Genetic factors also likely in interpersonal relationships, decreased activity level play a role in outcome, although gene-association and and community participation, lower academic or work outcome studies are still in their infancy (Kurowski performance, impaired driving, and increased substance et al., 2012a; see Ch. 4). The most widely studied gene abuse (Rivara et al., 1994, 2011). Up to 50% of children regarding trauma is the apolipoprotein E4 (APOE E4) with TBI may eventually experience significant behavallele, which has been shown to predict worse outcome ioral disturbances, which may persist or worsen with in adult TBI patients (Teasdale et al., 1997; Smith time. Familial environment appears to moderate this et al., 2002; Nathoo et al., 2003). APOE studies in chileffect (Yeates et al., 2001; Taylor et al., 2002; Li and dren are even more limited, with only a handful of studLiu, 2012). Other neurologic issues may include posties conducted to date that show inconsistent results. Two traumatic seizures, cranial nerve deficits, motor deficits, studies associated APOE E4 with poor outcome after and spasticity (Kuhtz-Buschbeck et al., 2003). Physical severe pediatric TBI especially in younger children; disabilities are strongly predicted by open or multiple another showed benefit after moderate to severe head head fractures, closed fractures, and motor vehicle acciinjury; and yet another indicated no difference in neurodents. Long-term general medical consequences of pedipsychological outcome in school-aged children after atric head injury include nutritional issues, endocrine mild TBI (Blackman et al., 2005; Teasdale et al., 2005; disruption, and heterotopic ossification from immobility Brichtova and Kozak, 2008; Moran et al., 2009). (Rivara et al., 2011). One retrospective study did not find an association Outcome differs depending on the pathoanatomic between the APOE E4 gene and cerebral swelling at nature of the injury. Brain swelling has been cited as a autopsy after pediatric TBI (Quinn et al., 2004), and negative prognostic indicator (Walker et al., 1985; another prospective observational study suggested that Levin et al., 1992). Subdural hemorrhage is associated children with the APOE E4 allele may not tolerate high with 40% mortality rate because of its strong association cerebral perfusion pressure as well as those without with more widespread brain injury (Luerssen et al., 1988). the allele (Moran et al., 2009). At this time, however, Focal contusions and epidural hematomas have lower it is difficult to make inferences from these studies bemortality rates, with the exception of frontal epidural cause they use different methodologies, investigate hematomas, which are often associated with severe different end points, have small sample sizes, and conparenchymal injury (Alberico et al., 1987). Even mild tain other limitations that may confound results TBI with intracranial hemorrhage is associated with (Kurowski et al., 2012a). worse quality of life, communication, activity, and The role of other genes in recovery after adult TBI self-care 2 years postinjury (Rivara et al., 2011). Not surhave been investigated, including interleukin- and prisingly, secondary insults such as hypotension or hypdopamine-related genes (see Ch. 5); however, to date, oxemia are associated with increased morbidity and only catecholamine-related genes have been investigated mortality (Chesnut et al., 1993; McHugh et al., 2007). in children (Kurowski et al., 2012a). Preliminary data There is no consensus on the best method for assessing suggest that catecholamine-related genes may be associfunctional outcome in children (Langlois, 2000). Over the ated with executive functioning in young children last several years, there has been a substantial interna12 months after head injury, but these data are yet to tional effort to standardize data collection in TBI research be validated (Kurowski et al., 2012b). Large genetic assoincluding recommendations for outcome assessment ciation studies, including genome-wide association studtools for the pediatric population (McCauley et al., ies, are necessary to identify and elucidate the role of 2012). Commonly used tools are the Galveston Orientaother genes on outcome after pediatric TBI, which tion and Amnesia Test (GOAT) or the Children’s Orientamay be helpful for informing prognosis and managetion and Amnesia Test (COAT) to assess basic alertness ment in this population in the future. and attention. The Wee-FIM tests overall functional

SPECIAL CONSIDERATIONS IN INFANTS AND CHILDREN outcome, as does the Pediatric Glasgow Outcome ScaleExtended (GOS-E Peds) (Beers et al., 2012). The CDC recommends use of the Child Health Questionnaire (CHQ) and the Pediatric Evaluation of Disability Inventory (PEDI) (Langlois, 2000). Postinjury rehabilitation encompasses a wide range of medical and therapeutic services that are formulated based on each patient’s individual needs as well as community availability. Inpatient services are aimed at improving mobility and independence in activities of daily living. However, metrics for pediatric rehabilitation interventions are not always available, and facilities often vary in their adherence to prespecified quality of care indicators (Rivara et al., 2012). Despite the high incidence of pediatric TBI, there have been few studies investigating the effect of timing or intensity of rehabilitation or family social support services on recovery (Chua et al., 2007). Early, intensive, multidisciplinary rehabilitation programs for severe TBI and cognitive rehabilitation appear to decrease total length of stay and improve neurocognitive abilities in adults after severe TBI, but few data exist for adult patients with specific injury types, with less severe injury, or for pediatric patients (Chesnut and Marshall, 1991). The vast majority of pediatric TBI rehabilitation occurs in the outpatient setting, including home and school. While over 60% of children hospitalized for TBI have been found to receive at least one outpatient service, a significant portion of children remain with unmet or unrecognized rehabilitation needs, especially for cognitive services (Slomine, 2006). Early reintegration into a structured learning environment may be encouraged in schools, small groups, or through individualized educational programs. Socialization, mobility, computer-based and internet-based cognitive activities, and sports activities have been utilized for this purpose (Chua et al., 2007; Wade et al., 2010). The greatest portion of overall recovery takes place within the first 6 months to 1 year, with a slowing of recovery and plateauing occurring in the years that follow; nonetheless, children tend to have a longer recovery phase than do adults, showing continued improvement even 3 years out from injury (Brink et al., 1970; Mahoney et al., 1983; Costeff et al., 1990; Boyer and Edwards, 1991; Jaffe et al., 1995). Despite long-term deficits, even the most severely impaired children often show great improvement in overall functional status within the first few months of rehabilitation (Kramer et al., 2013). Most motor recovery occurs early on, with cognitive and intellectual recovery continuing into later years (Brink et al., 1970). One significant challenge of tracking children’s progress after TBI is differentiating between “true recovery” and normal developmental progression. A child’s brain,

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especially the prefrontal cortex, continues to develop well into the third decade of life. As a result, neurobehavioral sequelae of head injury that were not apparent or were considered developmentally appropriate in the younger child may become unmasked as the adolescent or young adult begins to meet increasing intellectual and functional demands in everyday life. Such “late” neurobehavioral deficits might include hyperactivity, inattention, aggressiveness, social withdrawal, apathy, and decreased motivation. In a small cohort of adolescents with TBI, transition into adulthood was characterized as follows: about twothirds graduated high school, one-third were employed, and almost three-quarters had social problems (Kriel et al., 1988). Overall quality of adult life at very long-term follow-up (mean 13.3 years) after pediatric injury decreases as severity of injury increases; however, this could be due to a number of other factors such as cognition, personality, and injury factors (Anderson et al., 2011). These neurobehavioral sequelae can be seen early in the acute to subacute phases in severely injured patients, but may be more subtle and easily missed in those with milder injury and may become more apparent with the passage of time (Filley et al., 1987).

FOLLOW-UP CONSIDERATIONS FOR CHILDREN While the members of the initial responding team may transfer much of the care of the head-injured child to other specialties over time, it is often the members of the acute care team who are most connected to the care of the child in the minds of the family members. For this reason, at least some opportunity for follow-up with members of the acute care team (e.g., trauma surgeon, neurosurgeon, and/or other acute care providers) can be very helpful for the family and for the patient. Parents often remember specific phrases used in the acute phase, and benefit from clarification and having a chance to express and review their understanding of the events. Misconceptions can be discussed, and expectations reoriented consistently among members of the treating team. Various phases of response to recovery can be anticipated, including elation at early improvement, followed by frustration at persisting and often silently disabling long-term deficits. The acute responders may be able to explain who in the complex care team is best at addressing what problem, and can refer patients and families for specific therapies and/or family counseling. Of additional benefit to follow-up for the acute responders caring for children is the opportunity to watch the child’s recovery unfold over time. Each case adds data to the clinician’s experience, and facilitates more informed and sensitive counseling when new patients present with traumatic brain injuries.

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SUMMARY Traumatic brain injury in the pediatric population is a major public health problem and is one of the most common diagnoses facing pediatric practitioners in various specialties. The treating clinicians can have a major and satisfying impact in avoiding preventable deterioration and in optimizing outcome for the patient and family. A number of important differences distinguish infants, children, and adolescents, but data are still lacking in a number of key areas regarding tailored treatment. Large database approaches as well as translational research offer promise for expanding our understanding of the best way to continue to improve outcomes for the large numbers of children affected by traumatic brain injury worldwide.

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