Handbook of Clinical Neurology, Vol. 112 (3rd series)Pediatric Neurology Part IIO. Dulac, M. Lassonde, and H.B. Sarnat, Editors© 2013 Elsevier B.V. All rights reserved

Chapter 95

Traumatic brain injury

KAREN MARIA BARLOW*

Division of Pediatric Neurology, Faculty of Medicine, University of Calgary,Alberta Children’s Hospital, Calgary, Canada

EPIDEMIOLOGY

Incidence

The global incidence of traumatic brain injury (TBI) isincreasing; this is largely due to increasing motor vehicleuse worldwide. Indeed the World Health Organizationpredicts that by 2020 traffic accidents will be the thirdgreatest cause of global burden of disease. TBI has beenreferred to as the “silent epidemic” by the Centers forDisease Control and Prevention (CDC) and others, be-cause of its vast incidence, associatedmortality andmor-bidity, and the pressing need for additional research(Langlois et al., 2004).

Not only is there a significant cost to the individual andhis or her family associated with TBI but there is also asignificant cost to society. Pediatric TBI is a substantialcontributor to the health resource burden in the UnitedStates, accounting for more than $1 billion in totalhospital charges annually (Schneier et al., 2006). Each yearin the United States, TBI in children (0–19 years of age) isassociated with 7000 deaths, 60000 hospitalizations,and> 500000 visits to an emergency department with aresultant cost of more than $1 billion in inpatient charges(Keenan and Bratton, 2006).

Injuries are the leading cause of death in children,accounting for 62% of all deaths in this population, withup to 50% of injury-related deaths being linked to TBI(Langlois et al., 2004; Keenan and Bratton, 2006). Al-though hospitalization for TBI has decreased over thelast 20 years, the admissions for moderate and severeTBI seems to have changed little although there has beena marked decrease in the hospitalization rate for mildTBI. In childhood the greatest risk of sustaining a TBIis in the first 5 years of life and the later teenage years(see Fig. 95.1; Yates et al., 2006). Some 1035 per

*Correspondence to: Dr. Karen Maria Barlow, Assistant ProfessoUniversity of Calgary, Alberta Children’s Hospital, C4-335, 28

Tel: þ1-403-955-2296, Fax: þ1-403-955-2922, E-mail: karen.barlow

100000 children less than 4 years of age are seen inthe ER each year, and 5.7 per 100000 die. Children in ur-ban areas and from lower socioeconomic circumstancesare seen more frequently (Yates et al., 2006). Adolescentshave the highest rates of hospitalization and death. Malesare more likely than females to sustain TBI at all ages(Langlois et al., 2004). Other risk factors includeattention-deficit disorder and behavioral difficulties.For an excellent review of the epidemiology of pediatricTBI see Keenan and Bratton (2006).

Etiology

The mechanism of injury varies with age, severity, andpopulation studied; the commonest causes are falls,motor vehicle accidents, sport/recreation activities, andassault/abuse. Falls are the commonest cause of injuryat all ages, especially the young child (and the elderly).In the author’s center, falls accounted for 55% of 1271consecutive children with TBI presenting to a pediatricemergency room (Fig. 95.2) (Barlow, personal communi-cation). As age increases, injury acquired during varioussporting activities and due to motorized vehicle acci-dents (MVAs) increases. Severe injuries are more oftencaused by MVAs except in the infant, where assault orabuse is the commonest cause. Inflicted (or abusive)TBI occurs in 21.4/100000 children under 1 year and suchinjuries in general carry a poor outcome (Barlow andMinns, 2000).

Sports-related TBI

Medical professionals and government bodies are in-creasingly recommending a healthy lifestyle which in-cludes a balanced diet and plenty of exercise. This isencouraged in the home and in the school. Sports-related

r, Pediatrics and Clinical Neuroscience, Faculty of Medicine,88 Shaganappi Trail NW, Calgary, AB, Canada T3B 6A8.

@albertahealthservices.ca

Age group

Mixed rural – female

Mixed rural – male

Urban – male

Urban – female00

–04

05–0

9

10–1

4

15–1

9

20–2

4

25–2

9

30–3

4

35–3

9

40–4

4

45–4

9

50–5

4

55–5

9

60–6

4

65–6

9

70–7

4

75–7

9

80–8

4

85+

Ra

te p

er 1

00 0

00 p

opn

02040

6080

100

120140

160

180200

Fig. 95.1. Attendance rates for moderate–severe head injury

per 100000 population for each 5-year age band by sex and

area of residence. From Yates et al. (2006) with permission.

Assault

Assault1%

Sports related33%

Fall55%

MVA

MVA2%

Other

Other9%

Sports related

Fall

Fig. 95.2. A pie chart demonstrating the etiology of TBI in

children (0–17 years) presenting to a pediatric emergency

room.

Table 95.1

Glasgow Coma Score (GCS)

Eye opening

Spontaneous

To speechTo painNil

E4

321

Best motor response

ObeysLocalizes

WithdrawsAbnormal flexionExtensor response

Nil

M65

432

1Verbal response

Orientated

Confused conversationInappropriate wordsIncomprehensible soundsNil

V5

4321

Total EþMþV 3–15

892 K.M. BARLOW

activities that are associated with TBI increase in inci-dence at 13 years of age (Keenan and Bratton, 2006).The use of legislation to implement the use of helmetswhile cycling has been shown to decrease hospitalizationsand deaths due to TBI (Wesson et al., 2008). As weencourage healthy lifestyles, preventativemeasures needto be strongly encouraged and perhaps legislated for.

SEVERITYOF TBI

It is rare that the degree of primary insult to the brain canbe quantified. Indirect measures such as the speed of thevehicle involved, height of the fall, and details of the con-tact surface can be collected to approximate the degreeof energy and momentum involved in the injury. There-fore, a variety of methods are used to try and quantifythe severity of the injury and these rely on physiologicalmeasurements postinjury.

Glasgow Coma Score

TheGlasgowComa Score (GCS) assigns scores to degreeand type of eye opening, speech, and motor response(Teasdale and Jennett, 1974) (Table 95.1). The minimumscore is 3 (no response on any item) and maximum scoreis 15,which indicates noabnormalities in those three areasof assessment. This is a simple, quick, and reliable scorewhen used by the experienced; however, it has poor

interrater reliabilitywhenused by the inexperienced.Var-iation in the time of assessment can also lead to varyingscores. Most investigators now use the first GCS post-resuscitation or on admission to the emergency room.AGCSof 3–8 is categorized as a severe injury, 9–12mod-erate, and 13–15 a mild injury. The verbal component ofthe score poses a special challenge in infants and prever-bal children. Onemodified scoring system for use in pre-verbal children (1–36 months) is demonstrated inTable 95.2 (Raimondi and Hirschauer, 1984). Anotherpromising system is the FOUR score (Cohen, 2009).

Posttraumatic amnesia

The duration of impaired consciousness is also an indi-cator of severity of TBI. Posttraumatic amnesia (PTA) isthe period of clouded consciousness with disturbedmemory function following TBI. There are differentways to assess this. One way is to interview patients ret-rospectively and ask them to recall their first memoriesafter the accident. Other more accurate methods involvethe measurement of cognitive and memory functions ona daily basis postinjury. One example is the Children’sOrientation and Amnesia Test (age 3–15 years). It con-sists of 16 items evaluating three domains of cognitivefunction: general orientation to person and place, recallof biographical information; temporal orientation; andmemory (immediate, short-term, and remote) (Ewing-Cobbs et al., 1990). PTA as estimated by COAT scorescorrelates with GCS and is more strongly related tooutcome at follow-up (Ewing-Cobbs et al., 1990). Mild

Table 95.2

Children’s Coma Score (Raimondi and Hirschauer, 1984)

Eye opening

Ocular pursuit

Extraocular muscles intact, reactive pupilsFixed pupils or EOM impairedFixed pupils and EOM paralyzed

E4

321

Best motor response

Flexes and extendsWithdraws from painful stimuli

HypertonicFlaccid

M43

21

Verbal response

CriesSpontaneous respirationsApneic

V321

Total EþMþV 3–11

TRAUMATIC BR

injury is classified as a length of PTA of less than24 hours, moderate injury is between 1 and 7 days, andsevere injury is where the PTA is longer than 7 days.

Mild TBI comprises 80–90% of all TBIs in childrenwhereas moderate (7–8%) and severe (5–8%) TBIs makeup a relatively small proportion (Keenan and Bratton,2006). Mild injuries are difficult to classify using theCOAT as it requires two assessments separated by24 hours. A modified version of the Westmeed PTAscore has been validated for use in mTBI assessed inthe emergency room (Table 95.3) (Shores et al., 2008).As many TBIs occur in the context of multiple injuries,

Table 95.3

Revised Westmead PTA Score (R-WPTAS)

Answer S

What is your name?*

What is the name of this place?*(if no answer give names of 3 hospitalsto choose from)

Why are you here?*

What month are we in?*What year are we in?*What town/suburb are we in?

How old are you?What is your date of birth?What time of day is it? (prompt:

morning, afternoon, evening)Picture 1 Show pictures

for 5 secondsPicture 2Picture 3

Total

*Overlapping questions between GCS and R-WPTAS. Answer: record ve

logical observations, respectively

other scores used to classify injury severity are also use-ful. When multitrauma has occurred the outcome isnearly always worse, due to secondary insults associatedwith multiple injury such as hypotension associated withblood loss, hypoxia due to pulmonary contusions, etc.Some commonly used scores assessing multitraumainclude the Abbreviated Injury Score, Trauma InjurySeverity Score (TRISS), and the Pediatric Trauma Score.

BIOMECHANICSANDPATHOPHYSIOLOGY

Primary brain injury is used to refer to the primary injuryto the brain and is not dependent on the etiology of theinjury. The mechanisms of primary brain injury may beone or more of the following:

Impact loading. Usually sustained in a fall or an impactfrom an object, this involves direct unidirectionalforces with local injury (skull fracture, epidural he-matoma, and/or underlying contusions). Some con-tusions may be relatively remote from the contactpoint, the “contre-coup” phenomenon, due to the“wave-like” propagation of forces through theparenchyma. The structure of the interior skull vaultplays a significant role in the localization of coupand contre-coup contusions, contre-coup injuriesbeing commonly seen in the inferior frontal and an-terior temporal lobes. Coup and contre-coup injuriesare rarely seen in the infant.

Inertial loading. Injuries that lead to rotationof theheadonthe neck lead to angular acceleration–decelerationforces within the cranium. A seminal series of

AIN INJURY 893

T1 Answer ST2 Answer ST3

Total Total

rbatim answer; ST1, ST2, ST3 score at first, second, and third neuro-

Fig. 95.3. CT scan demonstrating an extradural hematoma.

Ninety per cent are due to injury to themiddlemeningeal artery

beneath the relatively weak pterion region of the temporal

bone. Blood accumulating between the dura mater and the

skull results in the classical lentiform shape.

ARLOW

experiments in primates by Ommaya et al. (1968)demonstrated a marked increase in the severity of in-juries sustained if the headwas allowed to pivot on theneck after the animal had been rapidly accelerated.These animals showed increasing intracranial pathol-ogy as rotational acceleration–deceleration forcesincreased. The lowest rotational forces to produce in-jury led to tearing of the subdural bridging veins (andresultant subdural and subarachnoid hemorrhages).Increasing forces led to shearing injury of axonsand capillaries at the gray–white matter junctionresulting in axonal injury and petechial hemorrhage.The highest forces were associated with the greatestamount of intracranial pathology often involvingthe midbrain and brainstem; at this point the animalbecame apneic and hypotensive, surviving only withartificial resuscitation (Ommaya et al., 2002).

Other mechanisms of brain injury include penetratinginjuries (e.g., gunshot wounds), compression injuries(e.g., MVAs and abusive injuries), and blast injuries(e.g., military events, usually young adults).

The biomechanical forces in the pediatric populationoften differ from those of adults due to the relativelylarge head size, reduced muscular strength, and in-creased flexibility in the neck, which allow larger angularacceleration–deceleration forces to be transmitted to thebrain. As there is less CSF space around the brain, andunderdeveloped bony ridges of the anterior and middlecranial fossae, focal lesions are not seen as frequently ininfants and very young children, whereas diffuse injuryis more common. Therefore, the types of primary injuryvary by age and mechanism of insult. For example,inflicted TBI is associated with subdural hemorrhages,diffuse axonal injury, and focal or diffuse cerebralischemia (demonstrated using diffusion-weighted imag-ing) (Suh et al., 2001). Conversely, adolescents have asimilar pattern of injuries to adults, where contusionsand axonal injury are the most common pathologies.

894 K.M. B

COMMONPATHOLOGIES

Epidural hematomas

Epidural hematomas (EDH) accumulate beneath theinner skull table and above the dura (see Fig. 95.3). Theyare nearly always associated with trauma (linear forces)and are seen with or without a skull fracture. EDH is un-common in TBI, occurring in 1–6% of hospital admis-sions, and is rare in the infant and neonate as the durais very firmly adherent to the inner skull (Case, 2008).Consciousness may or may not be altered and a smallproportion of these children (approximately 10%) deteri-orate several hours after the injury, i.e., a lucid intervalfollowed by unconsciousness. Treatment may involve

surgical evacuation through a burr hole or craniotomy,especially if the maximum diameter of hematoma ismore than 18 mm, there is midline shift, or increasedintracranial pressure. The outcome is usually excellentor very good (Case, 2008).

Subdural hematomas and hemorrhages

Subdural hematomas (SDH) are common in pediatricTBI and occur most frequently in the infant when theyare associated with inflicted TBI. Nearly all SDHare due to trauma or avulsion of a dural bridging veinnear the venous sinuses. This can be due to impact(with or without skull fracture), or due to rotationalacceleration–deceleration forces seen with shakingwhiplash injury, but are also seen in normal neonatesprobably due to the overlapping of skull bones duringchildbirth (Levin et al., 1997; Whitby et al., 2004). Theseneonatal subdural hemorrhages are usually subclinicaland resolve within 1 month. The common causes of ac-cidental subdural hemorrhages at older ages – vehicularaccidents, falls from height, and sporting events – arenot common causes of subdural hemorrhage in infantsand young children.

BR

It should be noted that some accidents involvingyoung children do lead to angular acceleration–deceleration forces to the head (such as falls fromswings in motion, etc.) where subdural hemorrhagescan be seen and that occasionally these have causeddelayed deterioration and death. Therefore, the impor-tance of taking a good history cannot be stressedenough, examining for factors such as: height of fall,type of flooring (carpet, wood, etc.), activities whereacceleration–deceleration forces could occur (i.e., rock-ing horses or swings), and the speed of vehicle, etc.Physicians working in the area of child abuse are advisedto review biomechanics associated with infantile TBI.

The clinical presentation of subdural hemorrhage isvery variable and much of this is due to the associatedparenchymal injuries acquired at the time of injury. Out-side of the period of infancy, SDHs present slowly andare often associated with drowsiness, lethargy, increas-ing headaches, and irritability. Although some requireneurosurgical evacuation, most gradually resolve withconservative management. Some develop into a chronicsubdural hematoma or subdural hygroma (see Fig. 95.4).

TRAUMATIC

Diffuse axonal injury and traumaticaxonal injury

Diffuse axonal injury (DAI) is a term originally used todescribe the injuries seen as a result of shearing forcesthat occur with rotational acceleration–deceleration inju-ries. These are most commonly seen in motor vehicle ac-cidents and inflicted TBI. In addition to direct trauma,axons are also damaged by the secondary biochemicalcascades occurring over hours to days. Pathologicalstudies of DAI have revealed microscopic featurescorresponding to wallerian-type axonal degeneration,

Fig. 95.4. ACT scan of an inflicted traumatic brain injury in a 6-mo

and retinal hemorrhages. CT demonstrates an acute SDH (!). A ch

to CSF on CT but can be easily differentiated on MR (*).

which most prominently affects the corpus callosum,subcortical white matter, and dorsolateral aspect ofthe upper brainstem. As magnetic resonance imaging(MRI) techniques have improved, it is recognized thatmany similar radiological features can also be seen withmilder injuries but with a much reduced burden of injuryand the term “traumatic axonal injury” (TAI) has beenused for these more limited injuries.

AIN INJURY 895

BRAIN INJURIESDUE TOFALLS

As falls are the commonest mechanism of childhood in-jury and TBI, they deserve special mention. The greatmajority of childhood short distance falls do not resultin significant TBI. However, whether or not a particularTBI in a child has been caused by a fall is a commondilemma, because the history of a fall is a commonscenario falsely provided by caregivers in cases wherethe TBI is actually an inflicted injury.

Short falls

A large literature on short falls in young children has accu-mulated to assist in understanding what injuries occur incommon household falls during childhood and is summa-rized in an excellent review by Chadwick et al. (2008).The short falls that occur in and around the home are fromdistances of less than 1.5 m without any angularacceleration and are primarily associated with either noinjury or focal impact injuries such as scalp laceration orcontusions. About 1–3% of short falls in young childrencause a skull fracture. These fractures are generally simplelinear fractures, do not cross suture lines, and are rarely as-sociated with intracranial hemorrhage or neurological def-icit. The best current estimate of themortality rate for short

nth-old boy who presented with seizures, increasing head size,

ronic subdural hematoma can be seen which is almost isodense

AR

falls affecting infants and young children is less than 0.48deaths per 1 million young children per year (Chadwicket al., 1998). Any complex skull fracture (crossing suturelines, stellate, and/orassociatedwithsignificant intracranialpathology) occurring as a result of a household fall shouldbe viewed as suspicious and investigated further.

Falls from height

Falls from a height are a major cause of accidental injuryand death, especially in urban children where they arevulnerable to falling from tall buildings. One study of61 children under 16 years of age, admitted to a hospitalafter falling from a height (e.g.., window fall), found a50%mortality rate in thosewho fell from the fifth or sixthstorey (Barlow et al., 1983). Many of these deaths are pre-ventable and a target for both legislation and population-based safety education strategies.

BRAINMETABOLISM FOLLOWINGTBI

After a biomechanical injury to the brain there is an abruptand indiscriminate release of neurotransmitters leading tounchecked neuronal ionic flux. Excitatory transmitters(i.e., glutamate) lead to further neuronal depolarization,potassium efflux, and calcium influx. These ionic shiftslead to marked changes in cellular physiology (Giza andHovda, 2001). These changes include: energy metabolicdysfunction, alteration in neurotransmission, free radicalproduction, and changes in gene expression and resultantprotein synthesis. Failure to restore homeostasis and cor-rect cellular toxicity leads to intracellular water accumu-lation, i.e., cytotoxic cerebral edema (vasogenic cerebraledema occurs when the blood–brain barrier is disruptedresulting in extracellular water accumulation).

Cerebral energy metabolic dysfunction has been dem-onstrated in TBI, at least in adults, with disturbances inglycolytic and oxidative metabolism that vary in regionand over time. Hypermetabolism of glucose is thoughtto be caused by large transient transmembrane ionicfluxes and consecutive neuroexcitation. This hypermeta-bolism of glucose is not adequately met by concomitantincreases in cerebral blood flow, and leads to flow–metabolism uncoupling with the evolution of secondaryischemic insults. Although less is known about thechanges in these metabolic pathways in pediatric TBI,when we consider the increased cerebral glucose metabo-lism of children (peaking between 4 and 8 years of age),combined with the significant impairments in cerebralautoregulation that occur following pediatric TBI, the po-tential for cerebral energy crisis is greater.

It is likely that extracellular glutamate is increased inpediatric TBI, due to failure of membrane-bound ionpumps and calcium-mediated exocytosis, which leadsto increased intracellular calcium. This global activation

896 K.M. B

of glutamate receptors is an important cause of neuronalinjury. Further, increased reactivity of the postsynapticAMPA and NMDA-type glutamate receptors occurs fol-lowing pediatric TBI. This again leads to excitotoxicity,epileptic activity (posttraumatic seizures occurmore fre-quently in children, especially infants), and/or delayedcalcium-dependent cell swelling, damage, and death.

Free radicals are another important cause of cellulartoxicity. Increased calcium is sequestered in themitochon-dria resulting in the productionof amitochondrial-derivedsuperoxide which combines with NMDA-derived nitricoxide. The result is a highly reactive peroxynitrite whichcauses rapidly fatal cellular processes such as lipid perox-idation and DNA fragmentation.

SECONDARY BRAIN INSULTS

The strong association of a worse outcome with multi-trauma in most TBI outcome studies quickly led re-searchers to identify important causes of secondarybrain insults. These insults arewhere there is further injuryto the brain subsequent to the trauma itself. The most im-portant of these include hypoxia, hypotension, decreasedcerebral perfusion, and hypercarbia. These can occur notonly because of injury to other parts of the body but alsobecauseof involvementof theneurological cardiovascularand respiratory centers. Other mechanisms include hypo-natremia, seizures, posttraumatic vasospasm, secondaryhemorrhage,apoptosis, andperfusion–reperfusion injury.In the infant especially, hypoglycemia is another potentialsource of secondarybrain injury.Ashighlighted in thepre-vious section, secondary injuryalsooccursdue tocascadesof excitotoxicity with or without seizures, free radicalproduction, and a metabolic energy crisis.

Cerebral edema as well as extraparenchymal andintraparenchymal hemorrhages can lead to brain shiftacross structures leading to known problems seen in theherniation syndromes. These are often ominous and lifethreatening, and acute measures are needed to preventdeath. These shifts take place supratentorially (cingulate,uncal, central) and infratentorially (upward cerebellar andtonsillar herniation).

● Cingulate (subfalcine) herniation occurs when there

LOW

is herniation of brain tissue under the falx cerebri to-ward the contralateral hemisphere. This can lead toocclusion of the ipsilateral and contralateral anteriorcerebral arteries. The resultant cerebral ischemia andinfarction leads to further cerebral edema and moreserious herniation, such as transtentorial (central)herniation.

● Uncal herniation occurs when the uncus is pushed

medially and then caudally under the tentorium witheventual compression of the brainstem. Initially thereis compression of the ipsilateral third cranial nerve

BR

(parasympathetic fibers are affected first leading to afixed dilated pupil), followed by compression of theipsilateral posterior cerebral artery and resultant is-chemia. Compression of the contralateral crus cerebri(corticospinal and corticobulbar tracts) leads to ipsi-lateral hemiparesis, an important localizing sign.Withincreasing pressure and progression of the herniation,the brainstem becomes distorted. This is associatedwith a decorticate posture (another ominous sign), re-spiratory depression, and death.

TRAUMATIC

● Transtentorial (central) herniation occurs when

there is a downward shift of both temporal lobesand midbrain through the tentorium cerebelli. Thiscan stretch branches of the basilar artery (paramedianartery), causing them to tear and bleed, known asDuret hemorrhages. The result is usually fatal. Radio-graphically, downward herniation is characterized byobliteration of the suprasellar cistern.

● Tonsillar herniation or “coning” is due to a down-

ward shift of the cerebellum and brainstem, andacutely this is associated with ischemia to the me-dulla, hypotension, bradycardia, and apnea. The pat-tern of decerebrate posturing is an ominous sign.

NEUROIMAGING

In addition to the clinical examination and assessment,neuroimaging techniques are invaluable in the investiga-tion and treatment of TBI. The most frequent modalitiesused are CT and MRI. CT has a pivotal role in the man-agement of the patient with TBI in the emergency roomand the intensive care unit. It is excellent for investigat-ing the presence of intracranial hemorrhage, skull frac-tures, and cerebral edema with or without parenchymalshift, and determining the need for immediate surgicaland/or medical intervention. MRI provides better paren-chymal, posterior fossa, and brainstem resolution but isnot as readily available at night.

Advanced MR modalities such as susceptibility-weighted imaging (SWI), diffusion-weighted imaging(DWI), diffusion tensor imaging (DTI), and magneticresonance spectroscopy are increasingly being used toexpand our understanding of the pathophysiologicalmechanisms in acute TBI, detect axonal injury andrecovery, as well as increase our ability to predict out-come (Ashwal et al., 2006).

Susceptibility-weighted imaging

The paramagnetic qualities of blood products can beexploited using a modality called SWI. This is more sen-sitive in detecting hemorrhagic DAI lesions after TBI in

children compared with conventional MRI, allowing agreater appreciation for the extent of injury (see Fig. 95.5).

Magnetic resonance spectroscopy

Magnetic resonance spectroscopy (MRS) is a noninvasiveneuroimaging tool that allows in vivo analysis of neuro-chemicals and their metabolites in humans. Metabolitelevels vary by anatomical region and change rapidly asthe brain develops requiring the use of normal age-matched reference data for interpretingMR spectra fromchildren. MRS provides a sensitive assessment of neuro-chemical alterationsafter brain injuryandhas thepotentialfor providing early prognostic information regarding theclinical outcome in pediatric patients with head injury.

Diffusion-weighted imaging

DWI uses the differences of the diffusion rate of watermolecules in different areas of the brain. DWI can dif-ferentiate between lesions with decreased and increaseddiffusion compared with normal brain tissue. Restricteddiffusion is believed to reflect cytotoxic edema in con-trast to the increased diffusion that typically occurs withvasogenic edema. DWI is sensitive in the early detectionof acute cerebral ischemia and may reveal pathologywhen conventional MRI is normal. It is particularly use-ful in inflicted TBI where more extensive injuries areseen in over 80% when compared to conventional MRI.

Diffusion tensor imaging

DTI allows evaluation of white matter fiber tracts byassessing the degree and directionality of the diffusionof water in brain tissue. The diffusion of water is re-stricted by a number of variables, including myelin, cellmembranes, intracellular microtubules, and axonal pack-ing. Fractional anisotropy seems to be the most sensitivemarker of posttraumatic changes in a wide range of cog-nitive and motor outcomes (Ewing-Cobbs et al., 2008).

MANAGEMENT

The primarymanagement of TBI aims to prevent ormin-imize as many of the secondary brain insults as possibleand to maintain normal cerebral homeostasis to allow asmuch recovery and repair as possible. Adelson et al.(2003a) have published evidence-based guidelines forthe management of severe pediatric TBI.

Immediate resuscitation

Thirty per cent of deaths can be avoided by startingtreatment before reaching hospital. Treatment for TBIstarts at the site of injury where paramedics provide re-suscitation “in the field.” Any child with a severe

AIN INJURY 897

Fig. 95.5. (A) Left: fluid-attenuated inversion recovery (FLAIR) sequence onMRI demonstrates a cortical contusion underlying a

skull fracture in a 12-year-old girl who fell from a horse. It is more easily seen using susceptibility-weighted imaging, SWI (right).

(B) SWI improves the detection of blood products associated with diffuse axonal injury when compared to gradient echo MR in a

14-year-old boywith prolonged impairment of consciousness following a rotational acceleration–deceleration injury sustained in a

motor vehicle accident.

898 K.M. BARLOW

alteration in consciousness (GCS < 9) should have air-way management and ventilation. Intubation shouldbe performed only if there are skilled personnel avail-able. The aim of treatment is to provide adequate oxy-genation, normocapnia, and maintain a normal bloodpressure. Fluid resuscitation is often performed, espe-cially where there is multitrauma or decreased periph-eral perfusion. Analgesia should be used as well aselevating the head of the bed to 30 degrees to increasevenous drainage from the head.

Ventilation and normocapnia

Hyperventilation and hypocapnia was once thought tobe of benefit in managing increased ICP associatedwith TBI. However, hypocapnia leads to cerebral

vasoconstriction and decreased brain perfusion, whichcan lead to increased mortality and should be avoidedespecially in the acute resuscitation period. As it mayalso be detrimental to be exposed to hyperoxia as wellas hypoxia acutely, in the future we may see specificventilation techniques (such as high volume, low PEEP,and slow rate) in the management of TBI.

Neurosurgical intervention

Neurosurgical management is often vitally important inpediatric brain injury and may include: elevation of de-pressed skull fractures; evacuation of extraparenchymalor intraparenchymalhemorrhagewhere there issignificantcerebral shift or persistent hemorrhaging; and insertionof an intracranial pressure monitoring device when

GCS £ 8 Surgery if indicated

Insert ICP monitor

Maintain CPP (age-appropriate)

Yes

Sedation and analgesicsHead of bed at 30°

Is ICP elevated?

Carefullywithdraw

ICP treatment

Considerrepeat

CT scan

Is ICP elevated?

Is ICP elevated?

Second-tier therapy

Mild hyperventilation (PaCO2 30–35 mm Hg)

Mannitol

May repeat if serumosmolarity < 320 m0sm

May continue if serumosmolarity < 360 m0sm

Hyperosmolar saline

Neuromuscular blockade

Drain CSF if ventriculostomy present

Yes

Yes

Yes

NoYes

NoYes

NoYes

NoYes

Yes

NoYes

Yes

NoYes

Is ICP elevated?

Is ICP elevated?

Is ICP elevated?

Fig. 95.6. Algorithm for first-tier management of elevated

intracranial pressure (ICP) in children following severe trau-

matic brain injury. CPP, cerebral perfusion pressure; CSF,

cerebrospinal fluid; GCS, Glasgow Coma Scale. From

Madikians and Giza (2009) with permission.

BR

necessary. These devices can be intraventricular, whichalso allows drainage of CSF, or intraparenchymal, whichmay also allows the surgeon/intensivist to performmicro-dialysis and measure metabolic markers of cerebral func-tion. Occasionally decompressive craniectomy (eitherunilateral or bilateral) may be performed as a life-savingmeasure when it is felt that the patient may still have achance of a good outcome.

Microdialysis

Microdialysis is still a research tool but one that we arelikely to hear more about in the future. To performmicro-dialysis a fine catheter lined with a dialysis membrane isplaced into the cerebral cortex. A number of metabolitescan be measured such as glucose, lactate, pyruvate, andglutamate. The microdialysate fluid is analyzed hourly.Markers of energy failure (e.g., elevation of the ratio oflactate to pyruvate) can then be investigated (Hilleredet al., 2005). Hopefully these techniques will allow us totailor the treatment to the individual in the future.

Intracranial pressure monitoringand treatment

ICP is dynamic and is determined by the balance of intra-cranial content volumes, i.e., CSF, blood, and brain.These volumes are often disturbed after TBI and canlead to increased ICP. Common mechanisms include: in-tracranial hemorrhage; increased cerebral blood flow(CBF) seen with vasodilation (hypoxia or hypercapnia),and/or “malignant cerebral edema”; cerebral edema(focal, i.e., contusions, and/or diffuse, i.e., diffuse axo-nal injury, hypoxic–ischemic injury, vasogenic cerebraledema); cerebral venous sinus thrombosis or decreaseddrainage; and increased CSF (due to obstruction in theventricular system) or decreased absorption from sub-arachnoid space (due to brain swelling, herniation, orsubarachnoid blood).

Cerebral perfusion pressure (CPP) is themean arterialblood pressure minus the mean intracranial pressure.CPP varies with age in children, and this should be takeninto account during the management of severe TBI.Elevated ICP and decreased CPP are critical variables as-sociated with poor outcomes and death. The adverseeffects of elevated ICP seem to be due to global ischemia(due to decreased CPP and CBF) or focal ischemia due tocerebral herniation. The benefit of ICPmeasurement hasnot been proven but is frequently performed in severeTBI, although less often in children.

ICP-guided/CPP-guided therapy

Many of the treatments of TBI are aimed at decreasingICP, “ICP-guided” therapy, and/or maintaining

TRAUMATIC

adequate CPP, “CPP-guided” therapy (Madikians andGiza, 2009). The interventions are based on maintainingeither normal ICP or normal CPP. One pilot study sug-gested improved outcome in the CPP-guided therapygroup when compared to the ICP-guided therapy group(Prabhakaran et al., 2004). Figures 95.6 and 95.7 demon-strate the first- and second-tier management strategiesbased on the guidelines for the management of pediatricsevere TBI (Adelson et al., 2003b; Madikians and Giza,2009). Although low CPP is associated with poor out-come, it is not clear which factor is more relevant: thetotal exposure to low CPP or a threshold value. Markersof energy failure such as the lactate–pyruvate ratio in thecerebral microdialysate may assist in the individual

AIN INJURY 899

Second-tier therapy

Yes

Yes

Yes Yes Yes YesYes Yes

Yes

Increased ICP despite first-tier treatment?No surgical lesion on CT?

Unilateral swelling? Bilateral swelling?

• Salvageable patient?• Evidence of swelling on CT?• Working ventri-

culostomy?• Open cisterns on current CT?

• Active EEG?• No medical contraindications to barbiturates?

• Evidence of ischemia?• No medical contraindications to hypothermia?

• Evidence of hyperemia?• No evidencce of ischemia?

• Consider hyper- ventilation to PaC02 < 30 mm Hg• Consider monitoring CBF, Sj02, AJD02

Consider lumbardrain

Consider unilateraldecompressivecraniectomy withduraplasty

Consider bilateraldecompressivecraniectomy withduraplasty

Consider high-dose barbituraters

Consider moderatehypothermia(32°–34°C)

Fig. 95.7. Algorithm for second-tier management of elevated intracranial pressure (ICP) in children following severe traumatic

brain injury, showing options for treatment of increased ICP intractable to first-tier interventions. AJDO2, arterial–jugular venous

difference in oxygen content; CBF, cerebral blood flow; EEG, electroencephalogram; SjO2, jugular venous oxygen saturation.

From Madikians and Giza (2009) with permission.

900 K.M. BARLOW

titration of CPP in the future. Hyperosmolar therapy(mannitol and hypertonic saline) are often used. Theirmechanisms of action include the induction of fluidshifts from the intracellular space to extracellular spaceand perhaps an antioxidant activity. For an excellentevidence-based review of specific therapies used in themanagement of pediatric TBI readers are referred toMadikians and Giza (2009).

Hypothermia

The role of cerebral cooling as a neuroprotective strategyis still uncertain. Hutchison et al. have performed thelargest multicenter randomized trial investigating cere-bral cooling in severe TBI (Hutchison et al., 2008). Nobenefit and potentially worsened outcome was foundin the treatment group. Further studies are ongoing withimproved control of perfusion and blood pressure dur-ing the re-warming period.

Hyperglycemia

The control of blood glucose following TBI has been thetopic ofmuch research in recent years.Hyperglycemia is anormal stress response frequently seen in severe TBI andis associated with increased catecholamine levels. Somestudies have suggested that glucose levels higher than11.1 mmol/L are associatedwith a 3.4-fold increase inmor-tality and intensive glucose control can decrease this (vanden Berghe et al., 2001; Griesdale et al., 2009). Stress hy-perglycemia may simply be a marker of injury severity,and a recent large randomized trial demonstrated thatintensive glucose control was not beneficial in reducingmortality (Griesdale et al., 2009). Worryingly, tight glyce-mic control has been associated with markedly decreasedglucose levels in cerebral microdialysate and elevation inmarkers of energy failure (Vespa et al., 2006). Therefore,

before adopting strategies aimed at tightly controllingblood glucose following TBI in children, there needs tobe further investigation.

OUTCOME

When discussing outcome of TBI in children it is impor-tant to mention the concept of plasticity as parents andfamilies these days will frequently ask about this. Plastic-ity is the capacity to vary in developmental pattern, phe-notype, or behavior according to varying environmentalconditions. Kennard first introduced the principle of neu-roplasticity in 1936 when she discovered that youngerchimpanzees were more likely to recover skilled actionsof the upper limb after focal destructive lesions whencompared to adult chimpanzees. She attributed this tothe fact that the brain was still developing. Kennard alsofound that the young chimps still had difficulty withcomplex motor tasks and she went on to report thatthey often developed problems later (Kennard, 1936).Nevertheless, her research led many to believe thatchildren had a greater potential for recovery after a braininjury than adults.

Plasticity may be beneficial or detrimental. For in-stance, the response of the brain to enriching environ-mental conditions in both animals and humans hasbeen shown to lead to increased dendritic arborizationand cognitive enhancement, and is most robust duringbrain maturation (Rosenzweig and Bennett, 1996). Incontrast, excessive stimulation of particular pathways,as may occur during seizures or other types of brain in-jury, can also promote abnormal neural connectionswhich interfere with normal cognitive development. Un-fortunately, since the 1990s it has becomemore apparentthat younger children with a TBI seem to have a worselong-term prognosis than older children and adults. This

12 months

Time since injury

0-3 months80

85

90

95

Ful

l Sca

le IQ

100

105

24 months

Mild TBI Mod TBI Severe TBI

Fig. 95.8. Full-scale IQ from acute stage to 24 months post-

injury in 70 previously neurodevelopmentally normal children

with mild (n¼24), moderate (n¼31), and severe (n¼15) TBI

(Catroppa and Anderson, 2003).

TRAUMATIC BR

may be because anatomical factors in children increasethe likelihood of diffuse injury, and plasticity has neverbeen demonstrated in diffuse injury.

There is a “dose–response” relationship between the se-verity of injury and the outcome (see Fig. 95.8). Followingsevere TBI in children, significant deficits in all areas ofcognition are seen and are especially marked in intellectualfunctioning and executive functioning (including proces-sing speed, attention, fluency, and problem solving), aswell as verbal immediate and delayed memory. Childrenwith moderate to severe TBI generally show significantimprovement in their neuropsychological functioningduring the first year postinjury, yet recovery often beginsto plateau after that (see Fig. 95.8) (Catroppa andAnderson, 2003).

Children with severe TBI not only fail to catch upwiththeir peers, but also appear to fall farther behind overtime and it appears to have the greatest effect in youngerchildren (Ewing-Cobbs et al., 2003). This reduced rate ofnormal developmental progress has been described as a“double hazard” injury model (i.e., severe TBI and youn-ger age at injury) (Anderson et al., 2005). Indeed, longi-tudinal studies suggest that children with severe TBI fallaway from their academic “growth curves” over timewith a significant and persistent decrement in academicskills compared to their peers.

Attention

Attention is needed in order to make a selection betweencompeting stimuli and enabling a response to the se-lected stimulus (activation) rather than another, i.e., in-hibit a response to a distracting stimulus (distractorinhibition). Attention is, therefore, required for most

neuropsychological tasks. While memory and attentionare not the same processes, many reviews in the litera-ture consider them together because persistent deficitsin areas of attention may contribute to any memory dif-ficulties seen.

Difficulty with attention is one of the commonestproblems encountered after TBI, and one that tends topersist (Dennis et al., 2008). Attentional difficulties canbe quite debilitating, as they have a deleterious impacton school performance and social/emotional function.Some children will satisfy criteria for attention-deficit/hyperactivity disorder (ADHD). ADHD is present in86–94% of children who had preinjury ADHD. WhereADHD occurs as a consequence of TBI, this is knownas secondary ADHD (S-ADHD). S-ADHD can be seenas early as 3 months postinjury and may persist for years.The occurrence of S-ADHD ranges from 14–18% at 12–24monthspostinjury (inchildrenwithoutpreexistingADHD).The inattentive symptoms peak at 6months postinjury andlater decline, whereas hyperactive-impulsive symptomsfluctuate for2 years andmaydiminish or persist. S-ADHDusually respondswell to similar stimulant therapies used inprimary ADHD.

Academic outcome

Parents identify the main difficulties for their children atschool as memory, attention/concentration, learningnew information, and school work. Ewing-Cobbs et al.examined school performance in children with severeTBI and found that 79% of the cohort had either re-peated a grade or were receiving special assistance inschool by a 2-year postinjury follow-up (Ewing-Cobbset al., 1998). Remarkably, many teachers are unawarethat a child in their class has suffered a TBI, and evenwhen they are aware they often do not realize that theTBI is related to the child’s educational difficulties.Not surprisingly, many children do not have any supportin the school system. In order to avoid this, there needs tobe ongoing long-term communication between parents,school, and the rehabilitation services.

Behavior

Cognitive and somatic symptoms tend to decline duringthe first year following the TBI. However, the secondyear is frequently troubled by emotional and behavioralproblems. Personality change is a well known, althoughnot well documented, clinical feature that is seen afterTBI and one that is the most distressing for families inthe long term. There are five major subtypes of person-ality change due to TBI: affective lability, aggression,disinhibited, apathetic, and paranoid. Sometimes thesepersonality changes are transient (most often affectivelability or aggression), may change with time, or begin

AIN INJURY 901

ARLOW

in the second year postinjury. Max et al. have found thatthis occurs in 22% of children in the first 6 months post-injury, and then declines to 12% in the 6–24-month periodpostinjury (Max et al., 2006). It is associated with injuryseverity and location, particularly injury involving thesuperior frontal gyrus. The onset is often associated withother changes such as the onset of S-ADHD, a majordepressive episode, or oppositional-defiant disorder.

902 K.M. B

Family outcomes

Any discussion of outcome of children with TBI wouldbe deficient if we did not take into account the outcomeof the family. The family creates an important learningenvironment for the child, and especially so after TBIwhere a poorer preinjury family environment seems tohave a detrimental effect on outcome (Yeates et al.,1997). Parents of children with TBI report higher levelsof psychological distress. They frequently have a heavyburden of care and often have physical and financial aswell as emotional difficulties postinjury and the effect isbidirectional: a poor outcome from TBI is associatedwith higher family distress and higher family distressseems to negatively impact the outcome from the TBI.Supporting the family, often for several years afterthe injury, is clearly an important part of the rehabilita-tion program.

Mild TBI

The terminology in mild TBI and its classification hasbeen the topic of much debate. Mild TBI is definedas an admission GCS score of 13–15, loss of conscious-ness (LOC) or altered mental state lasting less than20 minutes, absence of focal neurological deficits, andposttraumatic amnesia of less than 24 hours (The MildTraumatic Brain Injury Committee, 1993). The definitionis somewhat controversial in younger children where itcan be difficult to assess an altered mental state andperiod of amnesia.

As 16% of children have had at least one head injuryrequiring medical attention by 10 years of age, mTBI is asignificant public health concern (Langlois et al., 2004).Although there is widespread agreement that mTBI maybe associated with significant neuropsychological prob-lems, there is disagreement about whether such prob-lems can be attributed to the brain injury itself. Someresearchers suggest that preinjury factors such as age,alcohol abuse, education, neuropsychiatric history, andpostinjury factors such as stress and litigation affectthe recovery of persons with mTBI and contribute totheir disabilities (Iverson, 2006).

Postconcussion syndrome

Postconcussion syndrome (PCS), themost common entityto be diagnosed in peoplewho have suffered TBI, is a con-stellation of symptoms that includes physical, cognitive,emotional, and behavioral symptoms. The ICD-10 diag-nostic criteria for PCS require a history of TBI and at leastthree of the following: headache, dizziness, fatigue, irri-tability, insomnia, concentration difficulty,memory diffi-culty, and intolerance of stress, emotion, or alcohol(Boake et al., 2005). The DSM-IV criteria are similar ex-cept that the symptoms need to persist for 3 monthspostinjury.

The author (KMB) reports a large, prospective, con-trolled cohort study examining symptoms after mTBI inchildren (Barlow et al., 2010). Fourteen percent of chil-dren over 6 years of age were symptomatic at 3 monthspostinjury compared to 1% of children with extracranialinjury. Contrary to other studies, family functioning,and maternal adjustment did not explain the persistenceof symptoms. Some 2.3% of children continued to havesymptoms at 12 months, suggesting that the long-termoutcome is very good even though a few may havelong-term difficulties.

The morbidity associated with PCS should not beunderestimated, especially in this crucial time of neuro-logical and psychological development, and many scorepoorly on measures of functional impairment. The man-agement children whose symptoms persist longer than3 months can be difficult, especially as there is little re-search to support treatment options, and referral to aspecialist in rehabilitation is recommended. A usefulcomprehensive review of the literature and treatment op-tions by the Ontario Neurotrauma Foundation, “Guide-lines for Mild Traumatic Brain Injury and PersistentSymptoms,” can be found at http://www.onf.org.

INFLICTEDTBI (SEE CHAPTER 96)

Unfortunately inflicted TBI is not uncommon. The an-nual incidence is around 24.6 per 100000 infants (95%confidence interval 14.9–38.5) (Barlow and Minns,2000). Although the information is scarce, there are sim-ilar incidences in the UK and USA. It usually occurs invery young infants with a median age of 2–3 months(range: 2 weeks to 34 months) but can occur in toddlers,and there have been reports of “shaken” adults. Malesare more commonly injured (60%) and it occurs in allsocioeconomic circumstances. Inflicted head injury usu-ally takes place in the home and nearly always withoutother witnesses (91%). The perpetrators are most oftenmale, commonly the father or boyfriend, whereas the per-petrator is the mother in 15% and the babysitter in 5–30%of cases. The clinical picture includes an encephalopathy

BRAIN INJURY 903

presenting with one or more of the following: subduralhemorrhage, cerebral edema, retinal hemorrhages, andrib and/or metaphyseal fractures. It occurs in the contextof an inappropriate or inconsistent history and often withadditional evidence of other malicious injuries.

Children with inflicted TBI have a particularly pooroutcome. The mortality rate ranges from 11% to 30%and is higher than accidental head injuries in a similarage range, 6–12% (Barlow and Minns, 2000; Keenanand Bratton, 2006). These children have a higher morbid-ity than any other group of children or adults followingTBI, with 68% of children being abnormal on long-termfollow-up (Barlow et al., 2005). The range of neurologicalsequelae is great and mirrors the variety and extent of pa-thologies seen. The children need long-term medicalfollow-up asmany of the difficulties may not be apparentuntil the child reaches school age.

TRAUMATIC

CONCLUSION

This chapter provides an overview of many of the uniqueproblemsassociatedwith childhoodTBI. There needs to bemore research to help guide management strategies in thefield, in the intensive care unit, and in the home and school.Multidisciplinary care is vital and key team membersinclude: emergency medical teams, intensivists, neuro-surgeons, neurologists, pediatricians, psychiatrists, neuro-psychologists, psychologists, and neurorehabilitationtherapists. The most important members of the team,however, are thechildandfamily.Successfulmanagementwill be responsive to their needs and respectful of theirvalues at the different stages of recovery.

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