Pediatric Traumatic Brain Injury

Traumatic brain injury (TBI) is a global public health problem, affecting children and adolescents in every nation and demographic category, regardless of socioeconomic status. Public health efforts to lower pediatric TBI rates remain hindered by the difficulty in quantifying its frequency and severity because of regional variation in diagnostic capacity, definitions, and health care–related data capture.¹ That being said, the most recent estimates to date of the annual global incidence of pediatric TBI range from 12/100,000 children in Sweden to 486/100,000 children in Australia.¹ In a 2017 analysis using data from the US Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report, the incidence of TBI-related emergency department visits, hospitalizations, and deaths for US children is roughly 1000/100,000 pediatric population.² This translates to >640,000 annual visits to emergency departments (EDs), nearly 17,000 TBI-related hospitalizations, and 3000 TBI-related deaths among US children and adolescents age 0 to 17 years every year.³ For comparison, the incidence of childhood cancers in the US is 350/100,000 children, with roughly 11,000 new cancer diagnoses and 1,100 deaths among children under 15 years of age reported annually.⁴ In the United States, severe TBI accounts for 20% or fewer of all pediatric TBI cases, whereas concussion and mild TBI (mTBI) are diagnosed in nearly 5 million children and adolescents each year (comprising 70% to 90% of pediatric TBI cases presenting to EDs,⁵ respectively). Roughly 80% of pediatric mTBI cases are evaluated initially at outpatient appointments.⁶

Globally, motor vehicle collisions and falls are the most common mechanisms of TBI followed by nonaccidental trauma and sports-related injuries.¹ Mortality rates from severe pediatric TBI worldwide range from 1% to 7%, or between 2.8 and 3.8 per 100,000 children <18 years of age annually.¹ The leading causes of TBI-related death in US children and adolescents are motor vehicle collisions and homicide. Penetrating TBI related to firearms, particularly when the intent appears to be suicide, is associated with mortality rates as high as 70%. Mortality after mTBI is very low, but 10% to 30% of people develop persistent postconcussion symptoms,⁷ leading to substantial morbidity.

Moderate and Severe Pediatric TBI

Moderate and severe pediatric TBI involves a primary injury that consists of direct mechanical disruption of brain parenchyma, resulting in a cascade of biochemical and cellular events associated with cell injury and death. Secondary injuries are the result of both intracranial (eg, excitotoxicity, cerebral edema, cerebral ischemia) and systemic (eg, hypotension, hypoxemia, hypercarbia, hypocarbia) insults, which can occur minutes, hours, and days after the initial TBI. Emergency and critical care management of the moderate or severe TBI is focused on prevention, identification, and treatment of secondary injuries to optimize recovery.

Initial Assessment and Resuscitation

Immediate identification and correction of perturbations in physiology should take precedence in the prehospital and ED setting. This includes ensuring adequate oxygenation and ventilation and targeting age-appropriate blood pressures, with concomitant rapid assessment for severity of neurologic injury. Signs including pupillary dysfunction, extensor posturing, bradycardia, hypertension, and unilateral extremity weakness should the raise the suspicion of a possible mass lesion with intracranial hypertension, requiring emergent neurosurgical intervention. Inflicted head trauma is a special consideration in pediatrics and should be considered any time a child presents with alterations in consciousness without explanation or out of proportion with the stated mechanism of injury.

Patients with severe TBI likely will undergo orotracheal intubation in the prehospital or ED setting. A number of characteristics distinguishing the pediatric airway from the adult airway are important to consider during orotracheal intubation, including smaller diameter and length, relatively larger tongue in the oropharynx, more anterior larynx, relatively long and floppy epiglottis, and the narrowest portion of the airway being below the glottis at the level of cricoid cartilage. Selection of induction agents for rapid sequence intubation is focused on preserving hemodynamic stability. Ketamine as an induction agent traditionally has been avoided in children and adolescents at risk for intracranial hypertension, but new data have begun to emerge supporting its use.⁸

Acute Management in the Pediatric Intensive Care Unit

After initial stabilization and determination of need for urgent neurosurgical intervention for mass lesions, care focuses on prevention, detection, and mitigation of secondary insult in the pediatric intensive care unit (PICU). The most recent guidelines for the management of severe pediatric TBI from the Brain Trauma Foundation were released in 2019.⁹ Intracranial pressure (ICP) monitoring has become a mainstay of monitoring in severe TBI cases in the PICU, although evidence supporting its use in improving outcomes is weak.⁹ The placement of an external ventricular drain can be used to monitor ICP, and has been thought to have the additional therapeutic benefit of cerebrospinal fluid (CSF) drainage to reduce intracranial hypertension. However, the ADAPT trial (Approaches and Decisions for Acute Pediatric TBI), a comparative effectiveness study including >1000 severe pediatric TBI cases, showed no benefit in 6-month outcomes for people undergoing CSF diversion.¹⁰

A treatment threshold of 20 mm Hg for intracranial hypertension has been recommended for pediatric TBI based on a mixture of small and large observational studies.⁹ Approaches to reduce intracranial hypertension include volume reduction of various compartments: CSF diversion (external ventricular drain), reduction in intracranial blood volume by avoiding hypercarbia or reducing metabolic demands (sedation), improvement in venous drainage (head of bed positioned at 30 degrees with head midline), and reduction in brain edema (osmotic effect of hyperosmolar therapies). Boluses of 3% hypertonic saline have a Level II recommendation in the most recent guidelines for control of ICP. No studies on the use of mannitol met the inclusion criteria for most guidelines. However, the ADAPT trial found that hypertonic saline was superior to mannitol for reduction in ICP during ICP crisis.

Cerebral perfusion pressure (CPP) is defined as the difference between mean arterial pressure and mean ICP. Under normal conditions, cerebral blood flow (CBF) is maintained across a wide range of CPP values. However, after TBI, autoregulation is disrupted, and adequate CBF may be maintained over a much narrower interval of CPP, putting the person at higher risk of ischemia or hyperemia. Current guidelines recommend a minimum CPP of 40 mm Hg to avoid secondary injury, but limitations in the literature, such as variability in methods of measurement of CPP, have precluded age-dependent CPP threshold targets.⁹

Therapeutic hypothermia has been a compelling area of exploration in pediatric TBI based on its role in reducing metabolic demands, inflammation, excitotoxicity, and acute seizures. However, multiple randomized controlled trials have failed to show a benefit on outcome, and current recommendations limit therapeutic hypothermia to rescue of refractory intracranial hypertension.⁹ Early posttraumatic seizures occur within 7 days of injury and are more frequent in pediatric than in adult TBI. Current recommendations suggest seizure prophylaxis after severe TBI, but there is no recommendation on the superiority of levetiracetam over phenytoin, to name two potential agents for this purpose. Continuous EEG monitoring has become more common in PICUs for patients at risk for neurologic injury and may be an effective adjunctive monitoring modality in children or adolescents with TBI.¹¹ Further prospective multicenter investigations are needed to determine the feasibility of EEG as an adjunctive modality to predict or detect secondary insult in children or adolescents with TBI.

Rehabilitation and Recovery

Population-based studies demonstrate the consequences of pediatric TBI on long-term outcomes. Increased risk of psychiatric disorders, lower educational attainment, higher incidence of disability, and premature mortality when compared with unaffected siblings have been reported in a Swedish national cohort.¹² People who experience TBI are well-known to have high rates of disability, cognitive injury, and mental health concerns.^13,14 The frequency, severity, and duration of these deficits vary widely based on mechanism and repetitiveness of injury, demographic characteristics of the population being studied, and the interval between injury and follow-up assessment, but often are associated with substantial impairments in quality of life of the children or adolescents and their families.¹⁵ Distinct from concerns about return to functionality and employment in adults who experience TBI, recovery after severe pediatric TBI is often focused on the need for emotional, cognitive, and social support; rehabilitation and assistance for any residual physical difficulties; and support around the return to education.¹⁵

Returning to school can be both normalizing and difficult after severe TBI. School not only is instructional but also the nexus of most childrens’ social environment. The benefits of returning to a routine, surrounded by peers, can be offset by differences in academic needs, physical functioning, personality, and emotional state after pediatric TBI. Anticipation of these needs can be instrumental in assisting families in understanding the full complement of issues that will need to be managed.¹⁶ Indeed, parents of children and adolescents who experienced severe TBI report variable experiences in achieving new accommodations and support at school, largely shaped by the knowledge of the school system and their health care providers about the educational options available, and the willingness of those parties to assist families in the transition back to school.¹⁷ To assist clinicians and families in keeping up-to-date with the rapidly evolving recommendations for return to usual activity after concussion, the CDC provides comprehensive guidelines (https://www.cdc.gov/headsup/index.html), as does the Brain Injury Association of America (https://www.biausa.org).

Concussion and Mild Pediatric TBI

Concussion and mTBI share pathophysiology with biomechanical brain injury, including ionic flux, glutamate release, metabolic perturbations, axonal stretching, and alterations in the neurovascular unit. The primary distinction of less severe TBI is the lack of overt cellular death and necrosis. Much of the pathophysiology of mTBI is reversible over time, which is reflected in the high proportion of people with mTBI who recover fully within a few weeks of injury.

Assessment and Acute Management

Unlike moderate to severe TBI, the diagnosis of mTBI largely relies on self-reported symptoms, with signs that may be evident only acutely. This provides additional challenges for pediatric providers, because verbal communication of symptoms is limited in very young children and may require finesse to elicit from older children and adolescents. Obtaining parental report is helpful, and most concussion assessment tools for younger children include some parental queries.

Up to half of all pediatric mTBI occurs in the setting of sports and recreation; however, unlike higher-level adult sports, youth sports often have limited medical personnel presence at sporting events. This requires other adults to be responsible for early evidence-based management of children with suspected mTBI, by making a go/no-go or removal from play decision to protect the child from repeat injury or impacts until such a time as a thorough medical assessment can be conducted. After mTBI, the brain has ongoing vulnerability to repeat impacts, with higher risks for repeat concussion, musculoskeletal injury, and longer recovery time for people who play through a concussion (ie, return to contact risk while still acutely symptomatic). Davis et al¹⁸ provide a systematic review of pediatric-specific management of sport-related concussion and a description of the Child Sport Concussion Assessment Tool (Child SCAT5). New updates from the Concussion in Sport Group, an updated Child SCAT6, and a new Child Sports Concussion Office Assessment Tool are expected in 2023.

For individuals with suspected pediatric mTBI presenting to the ED, there are validated pathways to determine the need for acute CT scanning that minimize the likelihood of unnecessary radiation exposure. The large majority of children and adolescents with mTBI can undergo observation safely without CT scanning. More recently, studies using a pupillometer demonstrated ability to distinguish between a pediatric group with concussion and controls.¹⁹

Treatment and Recovery

Past consensus concussion management guidelines advocated brain rest to avoid symptom exacerbation. However, both observational and randomized studies have demonstrated the efficacy of earlier return to cognitive and physical activity, particularly in children and adolescents. Furthermore, randomized controlled trials have shown more rapid recovery in those who participate in early aerobic exercise compared with controls.²⁰ For sport-related concussion, consensus recommendations are commonly based upon gradual return to activity, whether it be return to school or return to play. Whereas most people with mTBI recover over time, a substantial subset develop persisting symptoms after concussion. A large Canadian study developed and validated a clinical prediction rule that helped stratify children and adolescents based on risk of persisting postconcussion symptoms at 1 month,²¹ and this rule has been used successfully in the outpatient clinic setting early after concussion.

Parents often ask about screen time after mTBI or concussion. In a recent study of >100 adolescents and young adults, abstaining from electronic screen time within the first 48 hours after concussion was associated with a significantly shorter duration of symptoms compared with those with no acute screen time restriction.²² However, the beneficial effects of prolonged restriction from screens after concussion are unproven, and consideration should be given to potential detrimental effects of overly delaying return to screen-based education or communication.

Persistent Postconcussion Symptoms

The burden of persistent postconcussion symptoms is a major public health concern, particularly in the pediatric population. Whereas the large majority of children with concussions recover completely, those who develop persisting postconcussion symptoms experience a disproportionate level of disability and behavioral disturbances, including depression, anxiety, and self-harm.²³ This may be potentiated by a history of mental health concerns, as several studies of children and adolescents who presented to a multidisciplinary concussion clinic report longer recovery in people with a history of anxiety, depression, or headaches. Posttraumatic headache is a common persistent complaint, with distinct posttraumatic headache phenotypes (eg, migraine, cervicogenic, occipital neuralgia), which may point to different treatments. A recent study in patients from a pediatric concussion clinic showed that a migrainous posttraumatic headache phenotype was particularly associated with longer recovery.²⁴ By aligning interventions with underlying persistent postconcussion symptoms, it becomes possible to move beyond nonspecific waiting or resting and actively treating concussion and persisting postconcussion symptoms.

Conclusion

Pediatric TBI presents many challenges that distinguish it from adult TBI. These include important differences in the mechanisms of injury, epidemiology, developmental aspects of injury response, symptom presentation, assessment tools, and neuroplasticity of recovery. The level of evidence available for treatments in individuals under 18 years of age with TBI is less robust than that for adults; however, protecting neurologic function and facilitating optimal recovery in children and adolescents with TBI is critical for long-term brain development and improved public health.