Pediatric neurotrauma.

Traumatic brain injury (TBI) is the leading cause of death and disability in children over 1 year of age. Knowledge about the age-specific types of injury and how to manage children with neurotrauma is essential to understanding and recognizing the extent and degree of injury and to optimize outcomes. In this article, we review the epidemiology, pathophysiology, and clinical management of pediatric neurotrauma.

INTRODUCTION

Pediatric neurotrauma is the leading cause of death in children more than 1 year of age[1] and disability following pediatric neurotrauma is common, with a profound impact on functional long- term outcomes.[2] Neurotrauma includes traumatic brain injury (TBI) and spinal cord injury (SCI).

Epidemiology

TBI should be considered in all children following trauma, particularly in those with a suspicious mechanism of injury, loss of consciousness, multiple episodes of emesis, tracheal intubation, and extracranial injuries. Most children with multiple trauma have TBI and most trauma deaths are associated with TBI. Following TBI, 10-15% children are classified as severe with an associated mortality rate of 50%.[3] However overall mortality is lower in children as compared to adults (2.5% vs. 10.4%), but certain factors predict worse outcomes [Table 1].

Table 1

Predictors of poor outcomes after pediatric TBI

Each year, more than 450,000 children present to emergency departments (EDs) because of TBI. Fortunately, the majority of children (90%) suffers only from minor injuries and can be released home after triage in the ED. Nevertheless, 37,000 children with TBI require hospitalization, and up to 2,685 children with TBI per year do not survive their sustained injuries.[4]

Boys and adolescents present more frequently to the ED for TBI with a male to female ratio of 3:2.[4] Moreover, boys have a four times higher risk of fatal TBI compared to girls. Apart from gender and age, race also appears to have an impact on the risk of suffering from TBI. Recently, Haider and colleagues studied 7,778 pediatric patients between 2 and 16 years from the National Pediatric Trauma Registry[5] and concluded that African-American children have a less favorable clinical and functional outcome after TBI. Racial disparities in outcomes may be explained as the result of differences in health care and/or health status. The mortality rate was however identical for all studied races. The observed types of TBI and mechanisms of injury differ with child age and development. According to the CDC, falls are the most common mechanism for TBI. In the age group of 1-4 years, up to 94-132/100,000 children require hospitalization because of fall-related TBI. In school age, injuries are frequently due to the increasing mobility and need for transportation. Children increasingly suffer TBI from bicycle crashes; however, the other causes include car collision while walking or riding a bicycle.[6] In adolescence, injuries resulting from automobile crashes increase dramatically and are the most common cause with 4.70/100,000 deaths per year. In toddlers, falls result in direct contusions while in older children and adolescents, motor vehicle accidents can result in all types of head injury, especially diffuse, shearing injuries. Sports-related head injuries can also be important in these older age groups and represent a unique type of repetitive mild injury that can have cumulative effects.[7] In children younger than 13 years of age, it is estimated that passenger-side airbags kill more children than save with different mechanisms, depending on the age of the children.[8] In an infant in a rear-facing child-safety seat, the resultant injury causes skull fractures, brain contusion, and hemorrhage, whereas in a forward-facing front-seat, child injuries are not just confined to the cranium, and additional fractures or ligamentous injuries of the cervical spine are common.[9] Centers for Disease Control and Prevention (CDC) in the United States reports TBI-related death rates for the different age groups as follows: 5.7/100,000 (0-4 years), 3.1/100,000 (5-9 years), and 4.8/100,000 (10-14 years). This rate increases approximately fivefold (24.3/100,000) for patients between 15 and 19 years.

Patterns of injury

Children are more susceptible to TBI because they have a larger head to body size ratio, thinner cranial bones providing less protection to the intracranial contents, less myelinated neural tissue which makes them more vulnerable to damage, and a greater incidence of diffuse injury and cerebral edema compared to adults. Children have a higher incidence of increased intracranial pressure (ICP) following TBI than adults (80% vs. 50%). Diffuse TBI is the most common type of injury and results in a range of injury severity from concussion to diffuse axonal injury (DAI) and permanent disability.[10]

Pediatric TBI can be categorized into two types of injury: (1) primary injury, which is the consequence of the initial trauma or impact of force; and (2) secondary injury, which occurs as a complication of secondary insults following primary injury. Secondary injury is often underestimated but may be responsible for a significant secondary worsening of the prognosis and outcome.[11] Primary injuries can be extraaxial (e.g., epidural hematoma [EDH], subdural hematoma [SDH], subarachnoid hemorrhage [SAH], and intraventricular hemorrhage [IVH]), intraaxial (e.g., diffuse axonal injury [DAI], cortical contusion, and intracerebral hematoma), or vascular (e.g., vascular dissection, carotid cavernous fistula, arteriovenous dural fistula, and pseudo aneurysm).[12] Secondary injuries include both acute (e.g., diffuse cerebral swelling, brain herniation, infarction, or infection) and chronic injuries (e.g., hydrocephalus, encephalomalacia, cerebrospinal fluid [CSF] leak, and leptomeningeal cyst).[12]

Inflicted TBI

Inflicted TBI (iTBI), sometimes called nonaccidental injury, is a unique, devastating category of TBI typically occurring in young children under 2 years of age. Population-based studies estimate that 30/100,000 children younger than 1 year require hospitalization because of iTBI per year. In infants, inflicted trauma is a major cause of TBI and is associated with skull fractures, SDH, SAH, DAI with or without cerebral edema, and delayed hypoxic-ischemic injury. Child abuse injuries are also age dependent with more DAI in neonates (due to the “shaken baby mechanism”) and more focal lesions in older children when they are “beaten up.” In addition, strangulation or chest compression while shaking may result in additional hypoxic-ischemic injuries superimposed to the focal injuries.[13] Most iTBI deaths involve TBI. Children with iTBI commonly present with altered consciousness, coma, seizures, vomiting, or irritability. Histories are often lacking and injuries out of proportion to history or developmental milestone should alert clinicians to consider this diagnosis. The outcome is poor after iTBI.[14]

Physiology and pathophysiology

Cerebral metabolic rate, Cerebral blood flow, and Cerebral auto-regulation

Global cerebral metabolic rate (CMR) for oxygen and glucose is higher in children than in adults (oxygen 5.8 vs. 3.5 mL/100g brain tissue/min and glucose 6.8 vs. 5.5 mL/100 g brain tissue/min, respectively). Unlike in adults, CBF changes with age and may be higher in girls compared to boys. Following TBI, cerebral blood flow (CBF) and CMRO2 may not be matched, resulting in either cerebral ischemia or hyperemia but recent work demonstrates that the incidence of cerebral hyperemia is only 6-10%, and that CMRO2 may be normal, low, or high after TBI. Metabolic failure is an integral component of the pathological aftermath of TBI. The oxygen extraction fraction (OEF) is a valuable parameter for the characterization and description of metabolic abnormalities. Ragan and colleagues used a recently developed magnetic resonance (MR) technique for the measurement of oxygen saturation, to determine the whole-brain OEF in both pediatric TBI patients and in healthy controls. Injury and outcome were classified using pediatric versions of the Glasgow outcome Scale (GCS) and Glasgow Outcome Scale-Extended (GOS-E), respectively. They found that patients with TBI had depressed OEF levels that correlated with the severity of injury. In addition, the OEF measured within 2 weeks of injury was predictive of patient outcome at 3 months after injury. In pediatric TBI patients, low OEF-a marker of metabolic dysfunction–correlates with the severity of injury and outcome.[15]

Similar to adults, the incidence of impaired cerebral auto-regulation is higher following severe compared to mild TBI (42% vs. 17%), and children with impaired cerebral auto-regulation early after TBI may have poor long-term outcome.[16] One potential explanation for this association may be hypotension, which is common after pediatric TBI, and may lead to cerebral ischemia.

Intracranial pressure

In adults, normal ICP is between 5 and 15 mmHg compared to 2-4 mmHg in young children. Unlike the adult with relatively poor cranial compliance, the infant with open fontanels may be able to accommodate slow and small increases in intracranial volume by expansion of the skull. However, the rapid expansion of intracranial volume, small as it may be, can explain the not uncommonly encountered rapid deterioration in infants following TBI. The current indications for ICP monitoring and treatment threshold for increased ICP are given in Table 2.

Table 2

Select 2012 brain trauma foundation guidelines for the management of severe brain injury

Cervical spine and spinal cord injury

Approximately half of the children with cervical spine injury have concomitant TBI and the presence of TBI increases the risk of spine injury. The incidence of spinal cord injury (SCI) is low (1%) in children because of greater flexibility of their tissues compared to adults. Motor vehicle crash is the most common cause although sports injuries are a second common mechanism in adolescents. Half of all children with SCI die at the scene of the injury. In total, 60-70% of cervical spine injuries occur in children >12 years of age. Young patients have injuries to the upper cervical spine and this is related to the fulcrum of cervical motion (C1-C3). In children >12 years of age, the fulcrum moves down to C5-C6. A complete plain radiographic assessment of the cervical spine includes an anteroposterior image, lateral views of the cervicothoracic junction and odontoid views. Due to the increased proportion of upper cervical injuries in young children, adding cuts through C3 to the initial head CT should be considered. A child with normal cervical spine radiographs should be maintained with cervical spine immobilization until he/she can be thoroughly examined.

In children, cervical spine fractures can occur without a neurological deficit and a neurological deficit can occur without a fracture. A neurological deficit without a fracture has been termed SCIWORA (spinal cord injury without radiological abnormalities). SCIWORA was a diagnosis made in the pre-MRI era and, nowadays, most children have an MRI. SCIWORA can occur in the cervical or thoracic spine and the onset of neurological deficit is delayed in about one-fourth of children with SCIWORA. Symptoms include brief sensory or motor deficits initially with later onset of more severe signs. The majority of SCIWORA injuries appears to be due to flexion or hyperextension and is caused by ligamentous stretching or disruption without bony injury. Children with these injuries need to be treated with spine immobilization because recurrent injury can occur.

Imaging modalities

The diagnosis of TBI is primarily made by computed tomography (CT) of the brain and is associated with increased ICP. Patients with diffuse axonal injury (DAI) may initially have a normal CT scan despite significant neurological findings, and increased ICP; a repeat CT scan often shows secondary injury due to cerebral edema.[17] Pinto et al. state that especially in childhood, conventional MRI compared to CT scan is a better imaging tool due to its high sensitivity and specificity, better correlation with the outcome and lack of radiation. Though conventional MRI sequences are able to depict the precise anatomical location, extent, quality, and degree of TBI, functional MRI (fMRI) sequences give information about the microstructural (DWI/diffusion tensor imaging [DTI]), biochemical (magnetic resonance spectroscopy [MRS]), and hemodynamic (PWI) short- and long-term consequences and complications of TBI.[13]

Clinical Management

Initial assessment

The initial approach to the traumatized child involves the primary and secondary surveys, and definitive care of all injuries and the principles outlined in the 2012 Brain Trauma Foundation Guidelines for managing children with severe TBI in Table 2 are followed. The GCS score (modified for children) is the most commonly used neurological assessment [Table 3].

Table 3

Glasgow coma scale and modification for young children

Cervical spine immobilization

In infants <6 months of age, the head and cervical spine should be immediately immobilized using a spine board with tape across the forehead, and blankets or towels around the neck. In infants >6 months of age, the head should be immobilized either in the manner described above or by using a small rigid cervical collar. Children >8 years of age require a medium-sized cervical collar. The use of rigid cervical collars is essential as it prevents cervical distraction during laryngoscopy. Since children under seven years have a prominent occiput, a pad placed under the thoracic spine provides neutral alignment of the spine and avoids excessive flexion that may occur in the supine position. These two maneuvers are paramount in avoiding iatrogenic cervical spine injury.

Airway management

The most important therapy during the primary survey phase is to establish an adequate airway. The lucid and hemodynamically stable child can be managed conservatively but if the child has an altered mental status, attempts should be made to establish the airway by suctioning the pharynx, chin-lift and jaw thrust maneuvers, or insertion of an oral airway. Children with a GCS score <9 require tracheal intubation for airway protection, and management of increased ICP. Early treatment of hypoxia by providing oxygen and apnea by ventilating via bag mask or endotracheal intubation results in better outcomes in patients with moderate to severe TBI.[18]

Intravenous access

Obtaining vascular access in the traumatized child can be very challenging. A well-functioning 20-gauge or larger peripheral intravenous catheter will suffice for the induction of anesthesia. Saphenous veins are commonly used. A second intravenous line should be started after induction. In emergent cases, if peripheral access is unsuccessful after two attempts, an interosseous line should be placed.[192021] Central venous catheters should be inserted by experienced personnel.

Intravenous fluids

Unlike adults, children can become hypovolemic from scalp injuries and isolated TBI. Zebrack et al. suggest that early monitoring, recognition, and early treatment of both hypotension and hypoxia decrease mortality and increase survival in patients with moderate to severe TBI. Early treatment of hypotension involves placing an intravenous or intraosseous line and administration of bolus isotonic fluids.[18] Isotonic crystalloid solutions are commonly used during the anesthetic and for cerebral resuscitation. Hypotonic crystalloids should be avoided and the role of colloids is controversial. The use of hydroxyethyl starch is discouraged because of its role in exacerbating coagulopathy. The 2012 Guidelines suggest that there is insufficient evidence for the use of glycemic control after severe TBI to improve outcomes despite evidence indicating that posttraumatic hyperglycemia is associated with poor outcomes.[22]

Monitoring

Standard ASA monitors and invasive arterial blood pressure monitoring are essential. Central venous pressure monitoring may be useful. The internal jugular line may be safely placed and used without increasing ICP. Retrograde jugular venous cannulation can be useful to guide the degree of hyperventilation in patients with TBI but is not standard of care. ICP monitoring is useful during surgery involving extracranial injuries since cerebral perfusion pressure can be calculated but any preexisting coagulopathy must be treated prior to monitor placement. Urine output must be monitored. Hourly arterial blood gases and tests of coagulation need to be examined. ICP monitoring should be used to guide blood pressure management in children with TBI undergoing nonneurosurgical procedures. The 2012 Pediatric Guidelines recommend that if brain oxygenation monitoring is used, the maintenance of partial pressure of brain tissue oxygen (PbtO2) ≥10 mmHg may be considered.[23]

Cerebral hemodynamics (ICP and blood pressure)

The 2012 Pediatric Guidelines recommend a minimum CPP of 40 mmHg to be considered in children with TBI. A CPP threshold of 40-50 mmHg may be considered. There may be age-specific thresholds with infants at the lower end and adolescents at the upper end of this range.[24]

The presence of the Cushing's reflex and autonomic dysfunction might be the only indicators of increased ICP. While SBP <5th percentile defines hypotension, in the absence of ICP monitoring and suspected increased ICP, supranormal systolic blood pressure may be needed to maintain cerebral perfusion pressure (CPP). At a minimum, MAP should not be allowed to decrease below values normal for age by using vasopressors. At our institution, intravenous phenylephrine infusion is commonly used to treat hypotension and maintain CPP >50 mmHg.

Management of high ICP

The 2012 Pediatric Guidelines recommend that treatment of intracranial pressure may be considered at a threshold of 20 mmHg.[25] Intracranial hypertension can be initially managed through elevation of the head, neuromuscular blockade, and hyperosmolar therapy. The administration of hyperosmolar fluid to both lower blood viscosity and decrease intracerebral edema is among the most commonly used therapeutic options. The 2012 Pediatric Guidelines recommend hypertonic saline at effective doses for acute use ranging between 6.5 and 10 ml/kg and continuous infusion at the rate of 0.1-1.0 ml/kg/h for treatment of severe pediatric TBI associated with severe intracranial hypertension. Mannitol use in the dose range of 0.25-1.0 g/kg intravenous is used to acutely lower ICP but the evidence to support its use is not strong.[26]

Bennett et al. did a retrospective cohort study using Pediatric Health Information System database, to evaluate patterns of use for mannitol and hypertonic saline to control ICP in children with TBI and to determine whether the guidelines published in 2003 for severe pediatric TBI has any impacted clinical practice regarding osmolar therapy. They found that the use of hypertonic saline increased and the use of mannitol decreased as a result of 2003 guidelines, and these trends continued through 2008. Hypertonic saline and mannitol are used less frequently in infants as compared to older children, and in a significant number of cases, osmolar therapy was used without ICP monitoring, suggesting opportunities to improve the quality of pediatric TBI care. With limited high-quality evidence available, published expert guidelines appear to significantly impact clinical practice in this area.[27]

High-dose barbiturate therapy may be considered in hemodynamically stable patients with refractory intracranial hypertension, and while doing so, continuous arterial blood pressure and cardiovascular support to maintain adequate CPP are required.[28] Refractory ICP can be treated with thiopental infusions, but volume loading and inotropic support may be needed to counter myocardial depression and hypotension.[29] Etomidate may be considered to control severe intracranial hypertension; however, the risks resulting from adrenal suppression must be considered.[30]

The 2012 Pediatric Guidelines recommend CSF drainage through an external ventricular drain in the management of high ICP in children with severe TBI and also a lumbar drain in the case of refractory intracranial hypertension with a functioning EVD, open basal cisterns, and no evidence of mass lesion or shift on imaging.[31] If these maneuvers fail to control elevated ICP, decompressive craniectomy should be considered. Careful monitoring of blood gasses, minute ventilation, and end-tidal carbon dioxide tensions are recommended.

Current guidelines recommend the avoidance of prophylactic severe hyperventilation to a PaCO2 level <30 mmHg in the initial 48 h after injury, and if hyperventilation is used in the management of refractory intracranial hypertension, advanced neuromonitoring should be done.[32]

Indications for surgery

The major goal of surgery for TBI is to optimize the recovery of viable brain. Most operations deal with the removal of mass lesions for the purpose of preventing herniation, intracranial hypertension, or alterations in CBF. In general, unless small and deemed likely to be venous, epidural hematomas should be evacuated in comatose patients. Subdural hematomas that are associated with herniation, are typically thicker than 10 mm, or produce a midline shift of >5 mm should be surgically evacuated. Indications on intraparenchymal mass lesions include progressive neurological deterioration referable to the lesion, signs of mass effect on CT, or refractory intracranial hypertension. Penetrating injury may often be managed with local debridement and watertight closure, if there is minimal intracranial mass effect (as defined above). Patients with severe brain swelling as manifested by cisternal compression or midline shift on CT or intracranial hypertension indicated through the monitor are potential candidates for decompressive craniectomy (DC). The relatively increased frequency of diffuse swelling in the pediatric population makes children more frequently considered for such treatment. The 2012 Pediatric Guidelines recommend DC with duraplasty in pediatric patients with TBI who are showing early signs of deterioration or herniation or are developing intracranial hypertension refractory to medical management during early stages of treatment.[33] Unilateral craniectomy is appropriate for lateralized swelling; bifrontal decompression is selected for diffuse disease.

Csókay and colleagues from Hungary performed a retrospective case series of eight consecutive patients to call our attention to the optimal timing of DC in children. They concluded that it could be useful to perform DC at 20-22 mmHg ICP in young patients in order to prevent rapid brain swelling, if there is no possibility to perform durotomy within 20 min after the onset of raising the ICP. It is especially considerable in underdeveloped countries where the emergency route may not be well organized due to locations of building and lack of adequate staffing. At this point of time, it is difficult to recommend routine early DC as a standard of care for the prevention of brain swelling in children with severe traumatic brain injury until further evidence from controlled trials is available.[34]

SUMMARY

TBI is a major cause of morbidity and mortality in the pediatric age group. The mechanism of injuries in children is different as compared to adults and their impact on the developing brain result in unique primary and secondary lesions. Among children, the mechanisms vary widely by their age group. Pediatric TBI results in significantly large individual, family, and societal costs. Injury prevention in children is extremely important. Several steps such as the use of bicycle helmets and child passenger seats appropriately, and improvement in sporting equipment have been shown to reduce the head injury. Therefore, efforts to improve outcomes are extremely important. Although many general principles of managing pediatric TBI are similar to adults, there are unique anatomic, physiological, and pathophysiological features of children with TBI worth recognizing.