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14. Pediatric Acquired Brain Injury Acute Care and Rehabilitation Interventions

Anna McCormick MD FRCPC, Amber Harnett MSc, Pavlina Faltynek MSc, Mitchell Longval BSc, Caitlin Cassidy MD, Robert Teasell MD, Shawn Marshall MSc MD FRCPC

Abbreviations

ABI                        Acquired Brain Injury

ADHD                   Attention Deficit/Hyperactivity Disorder

AMAT-c                Amsterdam Memory and Attention Training for Children

BTX-A                   Botulinum Toxin Type A

CAPS                     Counsellor Assisted Problem Solving Therapy

CPP                       Cerebral Perfusion Pressure

DC                         Decompressive Craniectomy

GCS                       Glasgow Coma Scale

HTS                       Hypertonic Saline

ICH                        Intracranial Hypertension

ICP                        Intracranial Pressure

I-InTERACT          Internet-Based Interacting Together Everyday

IRC                        Internet Resource Intervention

nTBI                      non-Traumatic Brain Injury

PCT                       Prospective Controlled Trial

PTS                        Post Traumatic Seizure

RCT                       Randomized Controlled Trial

RH                         Retinal Hemorrhage

SBS                        Shaken Baby Syndrome

SMART                 Strategic Memory Advanced Reasoning Training Program

TBI                        Traumatic Brain Injury

Key Points


Head elevation may lower intracranial pressure, but have no effect on cerebral perfusion pressure in children post TBI.

Therapeutic hypothermia delivered for 24, 48, or 72 hours can decrease intracranial pressure more than normothermia treatment for at least 24 hours in children post TBI, however, intracranial pressure may increase during the re-warming period.

Therapeutic hypothermia delivered for 24 or 48 hours is not different than normothermia in terms of mortality, unfavourable outcomes, or complications (arrythmias, coagulopathies, infections) in children post TBI.

Therapeutic hypothermia delivered for 24 hours can cause a decrease in heart rate, blood pressure, and cerebral perfusion pressure compared to normothermia treatment in children post TBI; further, decreases in blood pressure and cerebral perfusion pressure are associated with the development of unfavourable outcomes.

Therapeutic hypothermia delivered for 48 or 72 hours increases anti-oxidant markers, and decreases brain injury markers in the cerebrospinal fluid compared to normothermia treatment in children post TBI.

Enacting a protocol change to have cooling blankets placed on the patient’s bed prior to arrival in the pediatric ABI inpatient unit may decrease duration of hyperthermic states and acetaminophen administration.

Spine injury severity, midline shift on CT scan, fixed pupils, abdominal injury, and subarachnoid hemorrhage are associated with mortality and unfavourable outcomes at 3 months post-TBI in a pediatric population that underwent hypothermia treatment.

Treatment with hypertonic saline or Lactate Ringer’s solution may decrease intracranial pressure and increase cerebral perfusion pressure proportional to the increase in serum sodium in children post ABI. However, hypertonic saline may cause lower rates of acute respiratory distress syndrome and a shorter hospital length of stay compared to Lactate Ringer’s solution.

Hyperosmolar therapy (3% hypertonic saline and mannitol) may not improve intracranial pressure, cerebral perfusion pressure, or serum osmolarity in children post TBI.

Hypertonic saline treatment might lower intracranial pressure acutely (30 min, 7.5% hypertonic saline) and for up to 72 h (3% hypertonic saline) in children refractory to standard therapy (Intracranial pressure>20 mmHg) post TBI, however, both concentrations increase cerebral perfusion pressure, serum sodium, and serum osmolarity.

Hypertonic saline (7.5%) treatment might cause hypernatremia, kidney injury, acute respiratory distress syndrome, and severe neurological impairment in children post TBI refractory to standard therapy (Intracranial pressure>20 mmHg)

A hypertonic saline-based protocol could increase favourable discharge disposition, but not neurological outcomes compared to non-protocol guided therapy in children post TBI.

Early (<30 min post episode) hypotensive treatment may reduce mortality in pediatric patients post TBI.

Compared to fentanyl (2μg/kg) and pentobarbital (5mg/kg), 3% hypertonic saline may reduce intracranial pressure and increase cerebral perfusion pressure more rapidly in pediatric patients post TBI.

The effect of fentanyl on intracranial pressure and cerebral perfusion pressure in pediatric patients post TBI is unclear, however, high-dose fentanyl and low-dose midazolam, used either alone or in combination, may increase intracranial pressure.

Pentobarbital administration may lower intracranial pressure and cerebral perfusion pressure in pediatric patients with refractory intracranial pressure post TBI.

It is unclear whether dopaminergic agents, including amantadine, improve emergence from disorders of consciousness post ABI, however, an amantadine protocol of 4mg/kg/d for a week followed by 6mg/kg may be a safe and effective regiment to follow.

Administration of dexamethasone can inhibit endogenous production of glucocorticoids in children post TBI. 

Administration of dexamethasone likely increases the risk of bacterial pneumonia, but does not improve intracranial pressure, neurological outcomes, or blood pressure in pediatric patients post TBI.

N-Acetylcysteine and probenecid administration likely increases N-Acetylcysteine cerebrospinal fluid levels and is not associated with adverse events or hospital length of stay, in pediatric patients post TBI.

Magnesium sulfate may not adversely affect intracranial pressure, cerebral perfusion pressure, or mean arterial pressure in children post TBI.

The presence of abusive head trauma, high PRISM III score, and low post-admission GCS score may be associated with mortality in pediatric patients post TBI, however, anemia and blood transfusions are not.

Coagulation assessments performed upon admission to the pediatric TBI inpatient unit may be prognostic indicators of favourable outcomes post TBI.

A decompressive craniectomy may improve intracranial pressure, cerebral perfusion pressure and be associated with improved GCS scores in children post TBI compared to those who do not receive the procedure.

A decompressive craniectomy may be just as effective as standard therapy at reducing intracranial pressure in pediatric patients post TBI.

A decompressive craniectomy may be associated with secondary complications such as infections, formation of hygroma, and insertion of a cerebrospinal fluid shunt, in children post TBI.

Predictors of poor outcomes after a decompressive craniectomy might include non-accidental head trauma, delay (>4 hours) in surgery following admission, and intraoperative bleeding that exceeds 300 mL, in children post TBI.

Supraciliary “keyhole” small craniotomies for the treatment of anterior frontal space occupying lesions may not be associated with major operative or post-operative complications in pediatric patients post ABI.

A burr-hole craniotomy without continuous drainage for the treatment of either a chronic subdural hematoma or a subdural hygroma may not be associated with complications in pediatric patients post ABI.

There may be no difference in mortality between pediatric patients with TBI who sustained a penetrating injury and were treated at either an adult or pediatric trauma center.

Cognitive behavioural therapy may reduce internalizing behaviour disorders and improve socialization in pediatric patients post ABI, especially in patients not receiving adjunct pharmacotherapy.

Self-monitoring training might improve on-task behaviour, but not accuracy in completing assignments or task engagement, in pediatric patients post TBI.

Behavioural therapies might reduce problematic behaviours, lower agitation, and increase autonomy in pediatric patients post ABI.

Counsellor-assisted problem-solving and internet resource interventions may be effective at mitigating behavioural problems in pediatric patients post TBI, however, conflicting evidence exists as to which is superior and who benefits the most.

Mental health services are commonly underutilized within the first two years of a TBI, regardless of treatment (counsellor-assisted problem-solving versus internet resource comparison), gender, race, age, or socioeconomic status.

Online parenting skills workshops may be superior to internet resources in acutely reducing caregiver stress, depression, or self-efficacy. However, such workshops are likely not effective at improving parent-child communication post ABI.

An online problem-solving program with therapist assistance may be superior to an internet resource comparison group at improving compliant behaviour and self-management in children post TBI.

Web-based teen problem solving intervention programs are effective in reducing parental depression, anxiety, and distress compared to an internet resource comparison group, especially in families with lower socioeconomic status.

Family-based interventions benefit children, adolescents, and their families following brain injury.

An app-based coaching intervention may be effective in raising confidence and participation in activities following a pediatric TBI or brain tumor.

“Stepping Stone Triple P with Acceptance and Commitment Therapy” may improve parental outcomes and short-term behavioural problems in children post ABI.

Face to face family problem solving therapy may improve internalizing behavioural problems in children post TBI, however, it may not impact parental distress or relationship satisfaction.

Family based rehabilitation might be superior to clinician-directed care to improve cognitive and physical outcomes in children following a TBI.

A family focused inpatient social work program may be just as effective as a usual care intervention in reducing feelings of trauma and grief in parents/caregivers of children post-TBI. However, parents/caregivers undergoing an inpatient social work program may report increased confidence in managing pediatric TBI and feelings of more supportive counselling, increased family resources, and awareness of medical issues than a usual care intervention.

Use of community resource coordinators post discharge may not improve functional outcomes in children post TBI.

Multidisciplinary outpatient programs may improve functional outcomes for children following ABI.

Online family problem solving interventions likely improve everyday functioning, specifically in the school and community domains, but not at home, in adolescents who have sustained a TBI.

Interventions directed at improving social interactions might be beneficial in children post TBI.

A dedicated hospital to school transition program may not provide any more benefit than increasing special education and behavioural service access (usual care) in children post TBI.

Amantadine appears to be safe and efficacious in decreasing undesirable behaviours and improving the rate of recovery in children post TBI

The Amsterdam Memory and Training program may improve selective, but not sustained attention in pediatric patients post ABI.

The Attention Improvement and Management (AIM) program may improve sustained, but not selective, attention skills in pediatric patients with TBI compared to healthy controls.

Attention-specific neuropsychological training improves cognition, attention and behavioral skills in pediatric patients post TBI.

A cognitive computerized training (CCT) program may be feasible for pediatric patients post TBI.

Evidence regarding the efficacy of methylphenidate in improving cognitive and behavioural function following pediatric TBI is conflicting.

Utilization of a pager in adolescents post TBI may help improve memory.

Utilization of a diary in combination with self-instructional training might temporarily improve memory in children post TBI.

Cognitive rehabilitation can improve intellectual function for children following brain injury.

Counsellor assisted problem solving programs may be effective in improving executive function in adolescents post TBI; especially older adolescents (14-17 years), adolescents who suffered a severe TBI, and those with poor speech.

The Strategic Memory Advanced Reasoning Training (SMART) intervention may improve high-order cognitive functioning in adolescents post ABI.

Goal management therapy may reduce parental ratings of their child’s executive dysfunction.

Therapist-assisted metacognitive treatment programs for pre-adolescents likely improve executive function and increase the use of metacognitive learning strategies post ABI.

Interventions that target problem solving may be effective at improving executive function and metacognitive abilities post ABI.

Speech therapy using electropalatography might improve articulation in children post TBI.

Peer-group training of pragmatic language skills might improve communication in children post ABI.

Injury-related information provided to participants and parents may not have an effect upon deficit self-awareness in children post TBI.

It is unclear whether upper limb lycra splints improve the quality of movement in children post TBI.

Constraint induced movement therapy may improve upper limb function in children post TBI, however, further research is required.

Virtual reality-based therapy focused on walking and balancing exercises may improve certain movements (pelvic and ankle kinematics) but not others (knee flexion) in pediatric patients post ABI.

Movement therapy using a Nintendo Wii console might improve motor coordination, as well as engagement and intensity of physical activity in pediatric patients post ABI.

Body-weight supported treadmill training with an exoskeleton combined with physiotherapy may be superior to physiotherapy alone at improving gait and motor function in pediatric patients post ABI.

A wearable ankle robot combined with a computer game interface might reduce spasticity and improve balance in pediatric patients post ABI.

Robot Mediated Therapy (RMT) combined with goal-oriented reaching tasks might improve upper limb motor function and spasticity in pediatric patients post ABI.

Botulinum toxin type A, when used in combination with adjunct therapy (physiotherapy and occupational therapy), may effectively reduce upper and lower limb spasticity to improve movement range of motion, in children and adolescents following ABI.

Intrathecal baclofen pumps may reduce upper and lower limb spasticity in children with hypoxic brain injuries, however, intrathecal pump implantation may be associated with complications such as infections and skin protrusions. Side effects may be mitigated by subfascial pump implantation.

Home based exercise programs likely improve functional balance, aerobic capacity, and dexterity in children with an ABI, however, after 6 weeks, they have similar effects.

Prophylactic phenytoin likely does not reduce early (< 1 week post injury) or late (>1 week post injury) seizures in children post ABI.

Patients receiving prophylactic levetiracetam may be more likely to develop post traumatic seizures if they are younger and have experienced abusive head trauma.

Enhanced immune enteral feeding formulas may not be superior to regular formulas in regards to improving caloric and protein intake, however, may have beneficial anti-inflammatory properties.

Initiating nutritional support earlier may result in a decrease in mortality and better outcomes in a pediatric population post ABI.

The PURPLE intervention for shaken baby syndrome may increase knowledge about crying and the effects of shaken baby syndrome among caregivers. It may also increase protective behaviours among caregivers, such as walking away during a period of inconsolable crying in their infant.

Education programs on infant crying and safety may be effective at informing parents about the dangers of shaken baby syndrome, helping change their behaviour, and reducing the number of shaken baby syndrome.

Introduction

Acquired brain injuries can be separated into two broad categories based on their etiology: Traumatic brain injuries (TBI) and non-traumatic brain injuries (nTBI). TBI is commonly caused by motor vehicle accidents, falls, assaults, gunshot wounds, and sport injuries (Greenwald et al., 2003) while nTBIs often caused by  focal brain lesions, anoxia, tumors, aneurysm, vascular malformations, and infections of the brain (Braga et al., 2005) Module 1: Introduction and Methodology).

Unfortunately, interruptions to normal child development are frequently caused by TBI. In the United States alone, it is estimated that 500, 000 children and adolescents with TBI are seen at hospitals every year (McCradden et al., 2019). TBI accounts for 9.6% of pediatric deaths (0-19) in Canada and 40% of pediatric deaths in the US (White et al., 2001). Overall, TBIs  are considered the leading cause of death in North America in those under the age of 19 (Guice et al., 2007; Kan et al., 2006; Kraus et al., 1990; Schunk & Schutzman, 2012; Young et al., 2004). Importantly, children under the age of 6 who sustain a TBI are at a greater risk of resultant mortality compared to children who sustain a TBI at an older age (Lichte et al., 2015). While not as common as TBI, nTBIs still place a large burden on the healthcare system. In Ontario, Canada, between 2003/04 and 2009/10 alone, approximately 17,977 nTBI episodes requiring care were reported in patients under 19 years (82.3 per 100,000 children and youth 19 years and under in Ontario, Canada) (Chan et al., 2016). The age group most likely to sustain an nTBI during this time were babies (0-4 yr), followed by late adolescents (15-19 yr) (Chan et al., 2016).

In several regions around the world the main cause of TBI in children is  motor vehicle accidents, including North America (Asemota et al., 2013), Saudi Arabia (Alhabdan et al., 2013), Italy (Gazzellini et al., 2012), the Netherlands (De Kloet et al., 2012), Australia (Amaranath et al., 2014), and South Africa (Okyere-Dede et al., 2013; Schrieff et al., 2013). Other causes of TBI include falls, bike related injuries, sport related injuries, and acts of violence (Schunk & Schutzman, 2012). Males are twice as likely as females to experience a TBI. Male children are more likely to experience an intentional injury (i.e., physical assault), and adopt risk-taking behaviour that may lead to injury, or a fall from great heights, whereas female children are more likely to experience a TBI in the home due to small falls (falls <2m) (Collins et al., 2013). Non-accidental trauma represents <10% of pediatric TBI with the highest rates being reported in Nigeria (10%) and Malaysia (9%), while only 1-8% of pediatric TBI in the United States is attributed to non-accidental trauma (Dewan et al., 2016). Although the majority of ABI cases and research centers around TBIs, nTBI rates in Ontario between 2003-2010 were reported as high as 22.7 cases/100,000 due to substance toxicity, 18.4/100,000 for primary brain tumour cases, and 15.4/100,000 for meningitis cases (Chan et al., 2016). Despite clear evidence of high rates of nTBIs, proper treatment and epidemiological literature is lacking in most types of nTBIs, and nTBIs as a whole. For example, there is currently very little epidemiological research and healthcare utilization on primary brain tumours in pediatric patients, in spite of the fact that they are the leading cause of cancer death in patients under 19 (Brain, 2018).

 

The early years of childhood are a time of much growth and change, during which the body and brain are growing and developing daily. A brain injury interrupts this complex pattern of growth and development and may lead to substantially increased variability in baseline skills. As such, there is a need for age/stage appropriate testing and rehabilitation programming, as well as longitudinal follow-up to address the increasing gap between the skills of the child and age appropriate peers. Further complicating rehabilitation, many children that sustain a TBI have behavioral problems, learning difficulties, and show a lack of restraint (Anderson et al., 2013). Mental health problems that are common post pediatric ABI include aggression, internalizing disorders, post-traumatic stress disorder, attention deficit hyperactivity disorder, and personality changes (Schachar et al., 2015). The residual effects of ABI are different between children and adolescents, perhaps due to the difference in developmental stage at the time of the brain injury. Older children more often have headaches, cognitive impairments, and behavioural disorders post TBI compared to younger children (Choe, 2016). The majority (90%) of children who sustain a TBI have mild brain injuries (Araki et al., 2017), however, those with more severe brain injuries have the potential for significant deterioration immediately post injury and further complications during rehabilitation (Schunk & Schutzman, 2012).

Due to the fact that the nervous system is still developing, treatment of a child with a TBI is quite distinct from the typical treatment of an adult with a brain injury. Rehabilitation for those who sustain head injuries can have a significant positive impact on not just the speed of recovery, but can also help to improve functional outcomes beyond what is expected from spontaneous recovery (Cope, 1995).

14.1 Acute Interventions

A brain injury is often discussed in two phases, the primary injury and the resulting secondary injury. The primary injury is defined as “mechanical damage sustained immediately at the time of trauma from direct impact, or from shear forces when the gray matter and white matter move at different speeds during deceleration or acceleration” (Schunk & Schutzman, 2012). A secondary injury is defined as the “ongoing derangement to neuronal cells not initially injured during the traumatic event. This ongoing injury results from “processes initiated by the trauma: hypoxia, hypofusion, metabolic derangements, expanding mass and increased pressure and edema.” (Schunk & Schutzman, 2012). Surviving a severe TBI requires a very rapid response in the acute phase (Gazzellini et al., 2012). This first section will discuss the treatments that may be used in the acute stages of TBI in a pediatric population.

One of the most important concepts in the acute care of TBI is the rise in intracranial pressure (ICP) that accompanies brain injury, and perpetuates secondary injury by increasing pressures within the cranium and reducing blood flow to the area (Doyle et al., 2016). Cerebral perfusion pressure (CPP) is the pressure gradient that drives cerebral blood flow. CPP is determined, in part, by intracranial pressure (ICP). Elevations in ICP reduce CPP and therefore reduce cerebral blood flow with the hypoxia ultimately resulting in substantial secondary injury post TBI. It is therefore crucial to take steps to reduce the frequency, amplitude and duration of raised ICP episodes in the acute phase post-TBI to mitigate the risk of secondary injury and negative outcomes. According to clinical guidelines, CPP should be no lower than 40mmHg and ICP no higher than 20mmHg for children post-TBI in order to prevent detrimental effects (Kochanek et al., 2012). Monitoring ICP levels is challenging as doing so requires invasive measurement. However, hospitals that utilize ICP monitoring at greater rates have been shown to produce lower rates of mortality and severe disability following TBI (Bennett et al., 2012). In addition, ICP monitoring may be effective in the early detection of elevated ICP, therefore reducing  poor outcomes after pediatric TBI (Kochanek et al., 2012). It is also known that children with severe TBI’s (Glasgow Coma Scale (GCS)<8) are at higher risk of intracranial hypertension (ICH) (Dixon et al., 2016). Current guidelines recommend ICP monitoring in the acute phase post TBI for children whose brain injury is classified as severe (Kochanek et al., 2012). Accordingly, in practice it has been observed that older children and those with more severe TBI’s are more likely to have their ICPs monitored (Sigurta et al., 2013).

Elevated ICP has been shown to be associated with high risk of death and poor neurological outcomes post TBI (Kochanek et al., 2012; Kukreti et al., 2014). Specifically, ICP>20mmHg at any time and increased numbers of hours spent with ICP above target have been shown to be associated with worse outcomes post TBI (Miller Ferguson et al., 2016). As such, once appropriate monitoring/investigation has led to a diagnosis of ICH, steps should be taken to reduce ICP. Multiple interventions to reduce ICP have been explored, including regulation of head position in bed, treatment with hypertonic saline, and treatment with decompressive craniectomies.

14.1.1 Non-Pharmacological Interventions

14.1.1.1 Head Position

Key Points

Head elevation might lower intracranial pressure, but have no effect on cerebral perfusion pressure, in children post TBI.

For children who are critically ill as a result of an intracranial processes such as a TBI, tumor, infection, or hydrocephalus, the position of the child’s head is important. The skull creates a fixed space in which the brain and the blood supplying it must co-exist, as such it is believed that elevation of the head, from 15° to 30°, encourages jugular venous drainage and a subsequent reduction in ICP (Bhalla et al., 2012; Marcoux, 2005). Of course, head elevation can also reduce the flow of blood into the intracranial space and consequently reduce cerebral blood flow – a complication which further exacerbates the original brain injury. As such, it is recommended that the clinician ensures that the child is “euvolemic prior to placing him or her in this position is important to avoid orthostatic hypotension” (pg 222; (Marcoux, 2005), thus reducing the chance of impaired CPP with head elevation. Despite a substantial body of research looking at effects of head elevation in adults who have sustained a TBI, little is known of its efficacy in children; existing studies are presented in Table 14.1.

Discussion

Agbeko and colleagues (2012) examined the impact of head elevation on ICP by randomly altering head position and measuring ICP and CPP responses. Results suggest that ICP decreased when the head of the bed was elevated by a minimum of 10 cm. If the head was elevated by a lower amount, ICP was found to increase. It is important to note that this effect occurred in most children, but not all (Agbeko et al., 2012). CPP was not found to change significantly as a result of adjusting the head of the bed, which contradicts the aforementioned concerns of decreased CPP after head elevation (Bhalla et al., 2012). The height and age of each individual should be accounted for before altering head elevation, as the decrease in ICP was associated with the change in vertical distance from the base of the skull to the heart, rather than absolute degree of incline (Agbeko et al., 2012). While the results of this study provide promising evidence supporting head elevation in pediatric patients post TBI, the lack of controls and randomization make it difficult to draw solid conclusions from the study. Further randomized, controlled studies are suggested to investigate this intervention.

 

Conclusions

There is level 4 evidence that head elevation may reduce intracranial pressure, but not cerebral perfusion pressure, in children post TBI.

14.1.1.2 Hypothermia

Key Points

Therapeutic hypothermia delivered for 24, 48, or 72 hours can decrease intracranial pressure more than normothermia treatment for at least 24 hours in children post TBI, however, intracranial pressure may increase during the re-warming period.

Therapeutic hypothermia delivered for 24 or 48 hours is not different than normothermia in terms of mortality, unfavourable outcomes, or complications (arrythmias, coagulopathies, infections) in children post TBI.

Therapeutic hypothermia delivered for 24 hours can cause a decrease in heart rate, blood pressure, and cerebral perfusion pressure compared to normothermia treatment in children post TBI; further, decreases in blood pressure and cerebral perfusion pressure are associated with the development of unfavourable outcomes.

Therapeutic hypothermia delivered for 48 or 72 hours increases anti-oxidant markers, and decreases brain injury markers in the cerebrospinal fluid compared to normothermia treatment in children post TBI.

Enacting a protocol change to have cooling blankets placed on the patient’s bed prior to arrival in the pediatric ABI inpatient unit may decrease duration of hyperthermic states and acetaminophen administration.

Spine injury severity, midline shift on CT scan, fixed pupils, abdominal injury, and subarachnoid hemorrhage are associated with mortality and unfavourable outcomes at 3 months post-TBI in a pediatric population that underwent hypothermia treatment.

A number of pathological mechanisms determine the extent and duration of traumatic brain injury in pediatric and adult populations. These mechanisms often involve the formation of free radicals, changes in ionic flux that lead to damage, ischemia, upregulation of neuroinflammatory pathways, neurotransmitter release (excitotoxicity), metabolic and mitochondrial dysfunction, as well as swelling (edema)  (Kochanek et al., 2012; Olah et al., 2018). Many of these mechanisms are temperature sensitive, whereby increased temperature accelerates these processes leading to further injury and neurodegeneration (Olah et al., 2018).  In this sense, therapeutic hypothermia has gained increasing interest as a possible neuroprotective strategy to attenuate the pathological mechanisms of TBI (Olah et al., 2018).

In animal models of TBI, moderate therapeutic hypothermia (32-33 °C) has been shown to prevent the onset of secondary injuries caused by hyperthermia (body temperature 38-38.5°C) (Zhao et al., 2017) (Bramlett & Dietrich, 2012) (Feng et al., 2010) (Dietrich et al., 2009). However, human clinical trials have led to more controversial results. In adults, clinical trials have demonstrated a relationship between hypothermia and improved neurological outcomes (increased Glasgow Outcome Scale scores) (Clifton et al., 1993; Marion et al., 1997). While in the pediatric population, there appears to be an association between hypothermia and an elevated risk of mortality post TBI (Sundberg et al., 2011). Furthermore, a meta-analysis conducted by Zhang et al. (2015) found that hypothermia was ineffective in improving neurological outcomes and increased the risk of mortality, as well as arrhythmias in children who sustained a TBI.. In this sense, lowering core body temperature may be harmful and put a child at risk for further complications. Therefore, it is important to conduct more clinical trials to understand the proper onset, duration, and outcomes of therapeutic hypothermia. Current hypothermic protocols vary and are administered over a period of 24, 48 and 72 hours, however further research is necessary   to evaluate its safety and efficacy in pediatric TBI.

Discussion

Several RCTs have investigated the efficacy of therapeutic hypothermia in children with severe TBI. All treatments were initiated within 24 hours of TBI onset and methods of delivering hypothermia included a blanket (Adelson et al., 2005; Adelson et al., 2013; Bayir et al., 2009; Beca et al., 2015; Hutchison et al., 2010; Hutchison et al., 2008) or cooling cap for localized  treatment (Li et al., 2009). The duration of treatment was 24, 48 or 72 hours.

In a study by Hutchinson et al. (2008), hypothermia treatment began a mean time of 6.3 hours post-admission and was maintained for 24 hours. The study found that despite a trend towards increased unfavourable outcomes and a higher mortality, patients in the hypothermia group were not significantly different than the normothermia group. Furthermore, it was reported that ICP was significantly lower in the hypothermia group during cooling (16, 24 hr) and significantly higher during rewarming (48, 72 hr) compared to the controls. Hypothermia treatment was also associated with a lower heart rate (at 24 hr), CPP (25-72 hr), and blood pressure (25-72 hr) compared to the normothermia group. A post-hoc analysis of the original study went on to discuss that patients in the hypothermia group experienced more episodes of hypotension (at 24 hr post treatment) and low CPP (at 25-72 hr) than the normothermia group, and that these outcomes were significantly associated with the development of unfavourable outcomes (Hutchison et al., 2010).   Similarly, in a retrospective cohort study, systolic blood pressure <75th percentile was significantly associated with a higher risk of in-hospital mortality after isolated severe TBI in children (Suttipongkaset et al.).

The majority of studies reviewed implemented a hypothermia protocol delivered for 48 hours (Adelson et al., 2005; Adelson et al., 2013; Bayir et al., 2009; Biswas et al., 2002). There were no significant differences between groups in mortality rates (Adelson et al., 2005; Adelson et al., 2013) or outcomes such as arrhythmias, infection, or coagulopathy (Adelson et al., 2005; Adelson et al., 2013; Biswas et al., 2002). Compared to the normothermia group, ICP was significantly lower in the hypothermia group within 24 hours post-treatment (Adelson et al., 2005), however this improvement was not observed after 24 h  (Adelson et al., 2005; Biswas et al., 2002). Total antioxidant reserve and glutathione levels in cerebrospinal fluid were significantly greater in the hypothermia group, highlighting the attenuated consumption of antioxidants with hypothermia treatment (Bayir et al., 2009). The biomarker for oxidative stress, cerebrospinal fluid F2-isoprostane, decreased during the monitoring period in both the hypothermia and normothermia groups, however there were no significant differences between groups. Both aforementioned findings indicate that cerebrospinal fluid markers may be beneficial tools to monitor effects of hypothermia on oxidative stress, a significant contributor to secondary damage post-TBI (Bayir et al., 2009).

The longest treatment time for hypothermia was 72 hours with an onset between 5-7 hours post-TBI (Beca et al., 2015; Li et al., 2009). There was no significant difference reported for infection, arrhythmias, bleeding (Beca et al., 2015) or blood pressure levels with these protocols compared to the normothermia groups (Li et al., 2009). A significant reduction in ICP was maintained at 72 hours when a cooling cap was used but no long-term follow-up was reported (Li et al., 2009). Levels of S-100 (Ca2+ binding protein), NSE (metabolic enzyme), and CK-BB (marker of brain damage) were all significantly lower in the hypothermia group, indicating that hypothermic treatment provided neuronal protection in children post-TBI (Li et al., 2009).

In one retrospective study, the effects of a hypothermia treatment protocol on an ABI inpatient unit were examined to determine associations between duration of hyperthermic state, acetaminophen administration, neurosurgical intervention, mortality, and length of stay (Lovett et al., 2017). The authors collected data from the patients at baseline, during the protocol change, maintenance phase, and second implementation of the protocol. They found that the median duration of hyperthermic state decreased throughout hypothermic protocol implementation (Lovett et al., 2017). This was achieved by varying the timing and duration of cooling blanket application to each patient’s bed. Two cooling protocols were used, with protocol one initiating cooling blanket application when they were hyperthermic, and protocol two implementing cooling blanket application before the presence of hyperthermia. The authors found that there was a significant decrease in administration of acetaminophen from baseline to implementation of protocols one and two (Lovett et al., 2017).

In a secondary RCT analysis, the authors investigated mortality and unfavourable outcomes at 3-months post-TBI after hypothermic treatment (Rosario et al., 2018). Using a stepwise regression analysis, the authors found that spine injury severity and a midline shift on CT scan were significantly associated with mortality at 3 months post-TBI (Rosario et al., 2018). Using a bivariate analysis, the authors found that fixed pupils, abdominal injury and presence of subarachnoid hemorrhage were significantly associated with unfavourable outcomes at 3 months post-TBI.

Conclusions

There is level 1a evidence that therapeutic hypothermia delivered for 24 hours is no different than normothermia at increasing mortality and unfavourable outcomes in children post TBI.

There is level 1a evidence that therapeutic hypothermia delivered for 24 hours may decrease intracranial pressure during cooling compared to normothermia in children post TBI.

There is level 1a evidence that therapeutic hypothermia delivered for 24 hours may decrease heart rate (24 hr post treatment), cerebral perfusion pressure (25-72 hr post treatment), and blood pressure (25-72 hr post treatment) compared to normothermia in children post TBI.

There is level 1a evidence that decreases in cerebral perfusion pressure and blood pressure during treatment with therapeutic hypothermia (for 24 hr) are associated with development of unfavourable outcomes in children post TBI.

There is level 1a evidence that therapeutic hypothermia delivered for 48 hours is no different than normothermia with respect to mortality or complications (arrythmias, coagulopathies, infections) in children post TBI.

There is level 1a evidence that therapeutic hypothermia delivered for 48 hours may temporarily (<24 h) lower intracranial pressure in children post TBI compared to normothermia.

There is level 1b evidence that hypothermia treatment maintained for 48 hours may preserve antioxidant defenses in children following a severe TBI, when compared to normothermia.

There is level 1b evidence that therapeutic hypothermia delivered for 72 hours with a cooling cap may improve short-term intracranial pressure (<72 hr) and reduce biomarkers of brain damage (S-100, NSE, CK-BB), compared to normothermia therapy in children post TBI.

There is level 4 evidence that hypothermia induced through cooling blankets placed on the patient’s bed may decrease the duration of hyperthermic state and acetaminophen administration upon arrival to the pediatric ABI inpatient unit.

There is level 1b evidence that spine injury severity and midline shift on CT scans, fixed pupils, abdominal injury, and subarachnoid hemorrhage are associated with mortality and unfavourable outcomes, respectively, at 3 months post-TBI in a pediatric population that underwent hypothermia treatment.

14.1.2 Pharmacological Interventions

14.1.2.1 Hypertonic Saline

Key Points

Treatment with hypertonic saline or Lactate Ringer’s solution may decrease intracranial pressure and increase cerebral perfusion pressure proportional to the increase in serum sodium in children post ABI. However, hypertonic saline may cause lower rates of acute respiratory distress syndrome and a shorter hospital length of stay compared to Lactate Ringer’s solution.

Hyperosmolar therapy (3% hypertonic saline and mannitol) may not improve intracranial pressure, cerebral perfusion pressure, or serum osmolarity in children post TBI.

Hypertonic saline treatment might lower intracranial pressure acutely (30 min, 7.5% hypertonic saline) and for up to 72 h (3% hypertonic saline) in children refractory to standard therapy (Intracranial pressure>20 mmHg) post TBI, however, both concentrations increase cerebral perfusion pressure, serum sodium, and serum osmolarity.

Hypertonic saline (7.5%) treatment might cause hypernatremia, kidney injury, acute respiratory distress syndrome, and severe neurological impairment in children post TBI refractory to standard therapy (Intracranial pressure>20 mmHg)

A hypertonic saline-based protocol could increase favourable discharge disposition, but not neurological outcomes compared to non-protocol guided therapy in children post TBI.

Early (<30 min post episode) hypotensive treatment may reduce mortality in pediatric patients post TBI.

Mannitol is the most commonly used drug in the treatment of ICH in adults, however, research supporting its use in the pediatric population is lacking. In this sense,  the use of mannitol in the treatment of pediatric ICH is neither supported or discouraged (Kochanek et al., 2012). Currently, hypertonic saline (HTS) is the most frequently used treatment for the acute management of ICP in children who have sustained a brain injury. Administration of HTS results in an increase in serum sodium and osmolarity, creating an osmotic gradient that encourages passive diffusion of water out of cerebral cellular and interstitial spaces, into blood vessels. This results in a reduction of cerebral water content, effectively lowering ICP (Khanna et al., 2000). Hypertonic saline is used more frequently in older children, children with intracranial hemorrhages and skull fractures, and children with severe TBI (Bennett et al., 2012). Although there is a move towards utilizing HTS, the appropriate concentration of NaCl remains elusive and a variety of different concentrations have been used in the literature, ranging from 0.1-23.4%. The methodological details and results from eight studies investigating HTS for the acute management of pediatric TBI are listed in Table 14.3.

Discussion

Fluid resuscitation using hypotonic lactated Ringer’s solution was compared to fluid resuscitation using HTS in children with a severe TBI during the first three days post-injury (Simma et al., 1998). There was an inverse relationship between sodium concentration and ICP and a direct relationship between sodium concentration and CPP (i.e., increased serum sodium concentration correlated with lower ICP and higher CPP). The children treated with HTS were reported to have a significantly lower frequency of acute respiratory distress syndrome (ARDS), a lower rate of occurrence of two or more complications and significantly shorter ICU stay in comparison to the lactated Ringer’s solution group. (Simma et al., 1998).

A study investigating the efficacy of hyperosmolar therapy (3% HTS and mannitol) in children post TBI was analyzed (Roumeliotis et al., 2016). All patients received 3% HTS, while all but 3 received mannitol in addition. It was found that both 3% HTS and mannitol administration was not associated with any improvements in ICP, CPP or increases in serum osmolarity. While the previous study did not find any benefit to hyperosmolar therapy, 3 studies were analyzed evaluating the use of HTS in patients where standard therapy failed to lower ICP below 20 mmHg (Khanna et al., 2000; Peterson et al., 2000; Rallis et al., 2017a). Intracranial pressure was controlled acutely (within 30 min) after 7.5% HTS (Rallis et al., 2017a), and for as long as 72 h post treatment with 3% HTS (Khanna et al., 2000; Peterson et al., 2000). In addition, increases were found in both patient CPP (Peterson et al., 2000; Rallis et al., 2017a) as well as serum sodium and osmolarity (Khanna et al., 2000; Peterson et al., 2000). Treatment with HTS was not without its complications however, as studies noted kidney injury (Khanna et al., 2000; Rallis et al., 2017a), hypernatremia, ARDS, and severe neurological impairment (GOSE=3-4) in a third of the patient population (Rallis et al., 2017a).

While evidence continues to mount in favour of using HTS as a means of lowering ICP in children, adherence to new guidelines has been questioned. A group led by O’Lynnger (2016) implemented a new treatment protocol based on the guidelines proposed by the Brain Trauma Foundation, which center around the replacement of mannitol with HTS in the treatment of TBI in children. The researchers compared patients with TBI who received treatment before implementation of the new guidelines, to patients who were treated after the implementation of the new guidelines and noted an increase in favourable discharge disposition in the post-protocol group compared to the pre-protocol group. Despite the change in disposition, no inter-group differences were noted patients GOS scores.

Finally, HTS and osmotic agents were analyzed as a means of resuscitating hypotensive patients post TBI. A study by Kannan et al. (2016) discovered that early (<30 min post hypotensive episode) treatment of hypotension, by mainly using HTS, was associated with a reduction in mortality compared to non-early hypotension treatment (adjusted RR=0.46). Conclusions from this study support early hypotension treatment in ABI patients post TBI, however, further studies are required to determine which agent is best at reducing mortality, as patients also received blood products (28%) and vasopressors (13%).

Conclusions

There is level 1b evidence that serum sodium concentrations are inversely proportional to intracranial pressure, and directly proportional to cerebral perfusion pressure, after hypertonic saline or Lactated Ringer’s solution therapy in children post TBI.

There is level 1b evidence that hypertonic saline is associated with a lower frequency of acute respiratory distress syndrome, shorter intensive-care unit stay, and lower rate of complications compared to treatment with Lactated Ringer’s solution in children post TBI.

There is level 4 evidence that hyperosmolar therapy (3% hypertonic saline and mannitol) may not improve intracranial pressure or cerebral perfusion pressure, or increase serum osmolarity, in children post TBI.

There is level 4 evidence that intracranial pressure can be lowered acutely (within 30 minutes) after 7.5% hypertonic saline treatment, for as long as 72 hours, using 3% hypertonic saline treatment in children refractory to standard therapy (intracranial pressure >20 mmHg) post TBI.

There is level 4 evidence that hypertonic saline treatment (3 or 7.5%) may increase cerebral perfusion pressure, serum sodium, and serum osmolarity in children refractory to standard therapy (intracranial pressure>20 mmHg) post TBI.

There is level 4 evidence that 7.5% hypertonic saline treatment is associated with hypernatremia, kidney injury, acute respiratory distress syndrome, and low Glasgow Outcome Scale- Extended score (3-4) in children refractory to standard therapy (intracranial pressure>20 mmHg) post TBI.

There is level 2 evidence that treatment of children with TBI following a new hypertonic saline-based protocol may increase favourable discharge disposition, but not Glasgow Outcome Scale scores, compared to therapy without guidance of a strict protocol.

There is level 4 evidence that early (<30 minutes post episode) hypotension treatment may reduce mortality compared to non-early hypotensive treatment in children post TBI.

14.1.2.2 Sedatives and Analgesics

Key Points

Compared to fentanyl (2μg/kg) and pentobarbital (5mg/kg), 3% hypertonic saline may reduce intracranial pressure and increase cerebral perfusion pressure more rapidly in pediatric patients post TBI.

The effect of fentanyl on intracranial pressure and cerebral perfusion pressure in pediatric patients post TBI is unclear, however, high-dose fentanyl and low-dose midazolam, used either alone or in combination, may increase intracranial pressure.

Pentobarbital administration may lower intracranial pressure and cerebral perfusion pressure in pediatric patients with refractory intracranial pressure post TBI.

Narcotics (fentanyl and morphine), barbiturates (pentobarbital), and midazolam are used in pediatric brain injury for sedation and analgesia and have been studied for their potential to reduce ICP levels (Guilliams & Wainwright, 2016). These drugs are often used for the treatment of ICH in pediatric TBI, with 91% of practitioners reporting the use of sedatives as a first tier therapy for ICH (Welch et al., 2016). However, conflicting evidence suggests that such drugs may actually increase ICP (Welch et al., 2016). This mechanism is not fully understood, but may be due to changes in cerebral blood flow, altered systemic hemodynamics or autonomic reflexes (Welch et al., 2016).

The aim of this section is to summarize the effects of these pharmacological agents on secondary injury following TBI within the pediatric population. As such, the methodological details and results from three studies investigating the use of sedatives and analgesics for the acute management of pediatric TBI are listed in Table 14.4.

Discussion

Within the sedatives and analgesics category, Shein et al. (2016) found that administration of 3% HTS yielded the fastest reduction in ICP and increase in CPP compared to Fentanyl (2μg/kg) and Pentobarbital (5mg/kg). This is critical due to the known detrimental effects of a transient period of ICH. Pentobarbital was shown to reduce ICP more gradually and without affecting CPP, whereas fentanyl decreased ICP but actually worsened CPP levels (Shein et al., 2016). In line with the previous studies, Welch et al (2016) found that fentanyl and midazolam were not effective treatments for episodic ICH when used alone or in combination with each other, and even went to suggest that they in fact may even increase ICH. Furthermore, there was no effect on CPP levels following treatment with fentanyl and midazolam (Welch et al., 2016).

Pentobarbital administration in older children (mean age range 6-10 years) with refractory ICH was effective at reducing and controlling ICP in 28% of cases (Mellion et al., 2013). When refractory ICH was not controllable with pentobarbital, there was a reduction in time to death and increase in risk of death (Mellion et al., 2013). Of those children with severe TBI who received pentobarbital, 81% had at least one documented episode of decreased CPP. Almost all participants required vasoactive medications, and together with low CPP episodes, these results suggest that pentobarbital treatment can be associated with cardiovascular compromise (Mellion et al., 2013). The current pediatric guidelines suggest that pentobarbital therapy may be considered for children that are hemodynamically stable with refractory ICH, after other standard therapies and managements have been attempted (Kochanek et al., 2012). The data from these studies has not shown any evidence to suggest otherwise, especially because safer alternatives, such as HTS, exist and have been demonstrated to be more effective at lowering ICP.

Conclusions

There is level 4 evidence 3% hypertonic saline may decrease intracranial pressure and increase cerebral perfusion pressure faster than fentanyl (2μg/kg) and pentobarbital (5mg/kg) in pediatric patients post TBI.

There is level 4 evidence that high-dose fentanyl, low-dose midazolam, and high-dose fentanyl in combination with low-dose midazolam may increase intracranial pressure in pediatric patients post TBI.

There is conflicting (level 4) evidence regarding whether or not fentanyl reduces intracranial pressure and improves cerebral perfusion pressure in children following a severe TBI. 

There is level 4 evidence that pentobarbital may lower intracranial pressure and cerebral perfusion pressure in pediatric patients with refractory intracranial pressure post TBI.

14.1.2.3 Dopaminergic Agents

Key Points

It is unclear whether dopaminergic agents, including amantadine, improve emergence from disorders of consciousness post ABI, however, an amantadine protocol of 4mg/kg/d for a week followed by 6mg/kg may be a safe and effective regiment to follow.

Disorders of consciousness are defined as  a range of conditions where consciousness is either altered or absent, and includes comatose, vegetative, and minimally conscious states (Giacino & Whyte, 2005). In theory, promoting arousal in children with reduced consciousness in the acute phase can facilitate early participation in rehabilitation, thus improving outcomes post-TBI (Evanson et al., 2016; Suskauer & Trovato, 2013). Dopaminergic agents increase the amount of dopamine in the brain with the goal of facilitating arousal and responsiveness (McMahon et al., 2009). Potential dopaminergic agents utilized in the treatment of disorders of consciousness include pramipexole, bromocriptine, methylphenidate, and amantadine, which is the most commonly used (Suskauer & Trovato, 2013). Pramipexole and similar agents, such as bromocriptine are direct dopamine agonists that work on post-synaptic sites. While methylphenidate increases the stores of dopamine that are released from pre-synaptic vesicles and amantadine predominantly blocks re-uptake of dopamine, increasing dopamine levels (Patrick et al., 2003). Given that  neurotransmitter systems are still developing in children, they may respond differently to dopaminethan adults (McMahon et al., 2009). As such, additional research investgating the use of dopaminergic agents in a pediatric population is necessary.

Discussion

The results of studies assessing the effects of dopaminergic agents on improvements in arousal and responsiveness post-ABI are conflicting and sparse. Patrick et al. (2003) initially conducted a retrospective review of children who received one of a variety of dopaminergic agents. Overall, there was an increase in responsiveness in these children, despite the difference in mechanism of action for each drug (Patrick et al., 2003). This study lacked a comparative control group and studied a variety of drugs but provided preliminary results for future Randomized Controlled Trials (RCT)s.

Further studies were then conducted regarding the effects of amantadine on disorders of consciousness (McMahon et al., 2009; Patrick et al., 2006). One RCT found that standardized measures of arousal and consciousness did not significantly improve in children treated with amantadine, however, blinded physicians’ ratings of consciousness, but not arousal, improved significantly (McMahon et al., 2009). Authors hypothesize that the effectiveness of amantadine may be determined by etiology of brain injury, but lacked a separate analysis for TBI, stroke, and anoxic injury (McMahon et al., 2009).

Vargus-Adams et al. (2010) analyzed the pharmacokinetic properties of amantadine as a follow up to McMahon et al. (McMahon et al., 2009) and concluded that a dosage of 6 mg/kg per day was an effective and safe dose for a pediatric ABI population. At higher doses, amantadine caused nausea and vomiting. Therefore, the authors recommend beginning with a dose of 4 mg/kg per day and then increasing to 6 mg/kg per day after a week, to ensure minimal in side effects (Vargus-Adams et al., 2010).

Conclusions

There is level 1b evidence that amantadine may not improve level of consciousness (Coma/Near-Coma Scale, Coma Recovery Scale Revised, or Wee-FIM scores), but may improve blinded physicians’ ratings of consciousness, compared to placebo in pediatric patients post ABI.

There is level 1b evidence that an amantadine administration consisting of 4 mg/kg/d for a week followed by 6 mg/kg may be a safe and effective protocol compared to placebo in pediatric patients post ABI.

There is level 4 evidence that dopaminergic agents may increase responsiveness (Western NeuroSensory Stimulation Profile scores) in pediatric patients post ABI.

14.1.2.4 Corticosteroids

Key Points

Administration of dexamethasone can inhibit endogenous production of glucocorticoids in children post TBI.

Administration of dexamethasone likely increases the risk of bacterial pneumonia, but does not improve intracranial pressure, neurological outcomes, or blood pressure in pediatric patients post TBI.

Numerous corticosteroids have been used in adult brain injury care including dexamethasone, methylprednisolone, prednisolone, prednisone, betamethasone, cortisone, hydrocortisone, and triamcinolone (Alderson & Roberts, 2005). Using such a broad spectrum of agents within diverse patient groups has made understanding corticosteroid efficacy difficult. Adding to this difficulty is a lack of understanding regarding the mode of action of steroids. Laboratory studies have associated corticosteroid use with reductions in wet brain weight, facilitation of synaptic transmission, reduction of lipid peroxidation, preservation of electrolyte distribution, enhanced blood flow, and membrane stabilization (Grumme et al., 1995). In the pediatric population, corticosteroids (dexamethasone) is thought to reduce vasogenic cerebral edema and thereby ICP (Fanconi et al., 1988), however there is a lack of evidence to support their use in pediatric brain injury. In addition, the most recent guidelines for the management of pediatric TBI do not suggest the use of corticosteroids to improve outcomes or reduce ICP (Kochanek et al., 2019).

Discussion

The pediatric data highlights that dexamethasone suppresses endogenous production of glucocorticoids, compared to controls (Fanconi et al., 1988; Kloti et al., 1987) and that is does not provide any benefit for children with acute TBI. In addition to the suppression of endogenous glucocorticoids, excessive steroid present may lead to more severe side effects such as bacterial pneumonia (Fanconi et al., 1988; Kloti et al., 1987). Authors suggested that the lack of benefit with dexamethasone is due to the fact that the adrenal cortex can produce enough glucocorticoids on its own to elicit the maximum therapeutic effect on reduction of edema and membrane stabilization (Kloti et al., 1987). Therefore, dexamethasone is not superior compared to no steroid treatment at improving ICP, or neurological outcomes (GOS at 6 mo follow-up) and may even have detrimental side effects (Fanconi et al., 1988). The current pediatric guidelines recommend against dexamethasone administration for severe TBI (Kochanek et al., 2012; Kochanek et al., 2019).

Conclusions

There is level 1a evidence that administration of dexamethasone may inhibit endogenous production of glucocorticoids compared to placebo in pediatric patients post TBI.

There is level 1b evidence that dexamethasone administration may not improve Glasgow Outcome Scale (GOS) scores, intracranial pressure, or blood pressure, but may increase the risk of bacterial pneumonia, compared to placebo in pediatric patients post TBI.

14.1.2.5 Other medications

Key Points

N-Acetylcysteine and probenecid administration likely increases N-Acetylcysteine cerebrospinal fluid levels and is not associated with adverse events or hospital length of stay, in pediatric patients post TBI.

Magnesium sulfate may not adversely affect intracranial pressure, cerebral perfusion pressure, or mean arterial pressure in children post TBI.

The presence of abusive head trauma, high PRISM III score, and low post-admission GCS score may be associated with mortality in pediatric patients post TBI, however, anemia and blood transfusions are not.

Coagulation assessments performed upon admission to the pediatric TBI inpatient unit may be prognostic indicators of favourable outcomes post TBI.

In addition to previously discussed pharmacological agents for the management of ABI/TBI in the pediatric population, a variety of other candidate therapeutic options have been reported in the literature including magnesium sulfate (MgSO4), N-Acetylcysteine (NAC) and blood transfusions. Magnesium sulfate may act as a neuroprotective agent as it targets several pathophysiologic mechanisms that produce secondary brain injury (Natale et al., 2007). In particular, MgSO4 has been shown to decrease cerebral vasoconstriction, attenuate reactive oxygen species and restore alterations within the cerebral environment (Natale et al., 2007). In animal models, it was found that a decrease in intracellular magnesium resulted in worse neurological outcomes (Natale et al., 2007). However, there is limited evidence for the use of MgSO4 in humans (Natale et al., 2007). In contrast, N-Acetylcysteine is an antioxidant and neuroprotective agent that has been used clinically for a wide array of conditions including major depression, neonatal asphyxia, and neurodegenerative diseases (Clark et al., 2017). NAC may prevent secondary brain injury by acting as an antioxidant directly via its thiol group or by aiding in the replenishment of glutathione under conditions of oxidative stress (Clark et al., 2017).  Lastly, several studies have shown an association between blood transfusions and poorer outcomes in patients with severe TBI in adults (Salim et al., 2008; Sekhon et al., 2012). However, these results may not be generalizable to the pediatric population as significant differences in cerebral blood flow exist between the two populations (Yee et al., 2016). In contrast to adults, one group reported that 79% of pediatric patients with TBI that received a blood transfusion demonstrated substantial improvements in brain oxygenation (Zygun et al., 2009). Although evidence-based guidelines have been created to optimize the management of pediatric patients with TBI, there is no consensus on when to provide blood transfusions (Yee et al., 2016).

Discussion

Magnesium sulfate administration post-TBI was not found to compromise hemodynamics, such as mean arterial pressure, ICP, and CPP in children (Natale et al., 2007). The importance of these findings resides in the fact that magnesium sulfate may work to target the pathophysiologic mechanisms involved in secondary injuries, without compromising systemic hemodynamics in children (Natale et al., 2007). However, long-term neurological outcomes of magnesium were not reported. Future RCTs addressing the effects of magnesium sulfate on the pathophysiologic mechanisms of secondary injury in ABI/TBI are necessary.

One case control study investigated the effects of anemia and blood transfusions on pediatric patients post TBI (Yee et al., 2016). While the study did not report any association between anemia, blood transfusions and mortality, it was noted that factors such as presence of abusive head trauma, increasing PRISM III score, and low GCS after admission were associated with increased mortality. The study was conducted in light of the reported association between anemia, blood transfusions and adverse outcomes in the adult TBI population, however, the results of this retrospective study suggest this association may not be present in the pediatric population. Further studies are required to properly elucidate any potential association.

In a retrospective review of pediatric TBI cases at a trauma center, Podolsky-Gondim and colleagues investigated whether tests of coagulopathy had been performed and what the relative outcomes were (Podolsky-Gondim et al., 2018). The authors found that coagulation assessments like prothrombin time, fibrinogen levels, and thrombocyte count when performed at admission were potential prognostic indicators of favourable outcomes (Podolsky-Gondim et al., 2018).

Conclusions

There is level 1b evidence that N-Acetylcysteine in combination with probenecid may increase N-Acetylcysteine levels in cerebrospinal fluid, but may not be different from placebo in its effect on intracranial pressure, temperature, Glasgow Outcome Scale (GOS) scores, hospital length of stay, or mean arterial pressure, in pediatric patients post TBI.

There is level 2 evidence that magnesium sulfate may not affect hemodynamics (intracranial pressure, cerebral perfusion pressure, mean arterial pressure) compared to placebo in children post TBI.

There is level 3 evidence that the presence of abusive head trauma, high PRISM III score, and low post-admission Glasgow Coma Scale scores, but not anemia and blood transfusions, are associated with increased mortality in pediatric patients post TBI.

There is level 4 evidence that coagulation assessments performed upon admission to a pediatric inpatient unit may be potential prognostic indicators of favourable outcomes post TBI.

14.1.3 Surgical Interventions

14.1.3.1 Decompressive Craniectomy

Key Points

A decompressive craniectomy may improve intracranial pressure, cerebral perfusion pressure and be associated with improved GCS scores in children post TBI compared to those who do not receive the procedure.

A decompressive craniectomy may be just as effective as standard therapy at reducing intracranial pressure in pediatric patients post TBI.

A decompressive craniectomy may be associated with secondary complications such as infections, formation of hygroma, and insertion of a cerebrospinal fluid shunt, in children post TBI.

Predictors of poor outcomes after a decompressive craniectomy might include non-accidental head trauma, delay (>4 hours) in surgery following admission, and intraoperative bleeding that exceeds 300 mL, in children post TBI.

Supraciliary “keyhole” small craniotomies for the treatment of anterior frontal space occupying lesions may not be associated with major operative or post-operative complications in pediatric patients post ABI.

A burr-hole craniotomy without continuous drainage for the treatment of either a chronic subdural hematoma or a subdural hygroma may not be associated with complications in pediatric patients post ABI.

The approach to management of individuals who sustain a severe TBI with refractory ICP and who have no evidence of a mass lesion, remains controversial (Kan et al., 2006). However, when interventions to manage elevated ICP fail, decompressive craniectomy (DC) may be a last resort to considered. (Kochanek et al., 2012; Ruf et al., 2003). The literature suggests that DCs are effective in reducing ICP and are associated with positive outcomes in children following a severe TBI (Jagannathan et al., 2007; Weintraub et al., 2012). Figaji et al. (2008) noted that in children who had sustained a severe TBI, DCs reduced diffuse brain swelling and improved ICP and cerebral oxygenation. Additionally, a systematic review revealed that favourable outcomes were observed after a DC regardless of the etiology of the ABI (Traumatic=60%, nontraumatic=69%), or whether it was performed within 24 hours compared to after 24 hours (61% versus 69% respectively) (Guresir et al., 2012). Based on a review of the literature from Weintraub et al. (2012) and the current pediatric guidelines (Kochanek et al., 2012), DCs are effective to manage ICP when ICP levels are hazardous to the child and cannot be alleviated non-surgically. However, the majority of studies are retrospectively conducted and further rigorous controlled trials are warranted to make definite conclusions regarding the effectiveness of DCs as an emergency treatment for ICP.

Discussion

Refractory ICP levels normalized or improved significantly after a DC in children (mean age 7.7-14.5yr) who had sustained a severe TBI (Josan & Sgouros, 2006; Ruf et al., 2003; Rutigliano et al., 2006). ICP improved more in children (mean age 10.1 yr) who underwent a craniectomy compared to children who received “standard” ICP management, although this difference was not statistically significant (Taylor et al., 2001). Furthermore, a recent retrospective study suggested that a DC may also improve cerebral perfusion, as it was found that the minimum CPP observed was significantly higher after the procedure as compared to before (Rallis et al., 2017b). In younger children (mean age 1.6 yr), an early DC (< 2 hr after admission) had a survival advantage of 16% compared to a late DC (2 hr post admission) and the mean pre-op ICP for patients who died was 27 mmHg, with 90% of these patients having ICP over 20 mmHg (Prasad et al., 2015).

Although ICP appears to improve for most children following a DC, it is important to consider other complications that may arise. Two studies examined post-operative complications to highlight the potential detrimental effects of a DC (Pechmann et al., 2015; Prasad et al., 2015). The most common complications following DCs were insertion of a cerebrospinal fluid shunt (16%), cranioplasty infection (16%), ventilator associated pneumonia (31%), formation of hygroma (15-83%), and development of post-traumatic hydrocephalus (18-42%). Other potential complications included epilepsy, secondary infections from the surgery, requirement of additional treatment, and septicemia (Pechmann et al., 2015; Prasad et al., 2015). Seventy five percent of children required further surgery due to complications from the initial DC (Pechmann et al., 2015). When comparing those who received a DC to those who did not, it was found that 66% of patients undergoing a DC made a full recovery (GOS=5) and the other 33% had a GOS of 4, while only 50% of the non-DC patients made a full recovery, two died, and one has a GOS score of 3 (Josan & Sgouros, 2006).

Significant predictors of worse outcomes following DCs include surgical delay >4 hours after administration and intraoperative blood loss >300 mL (Khan et al., 2014). Additionally, young children with non-accidental head trauma had higher odds of mortality following a DC (Oluigbo et al., 2012) and poorer outcomes (Adamo et al., 2009) compared to those with accidental traumas. The authors suggest that either DCs are not likely to change fatal outcomes in this group or that the threshold requirement for decompression should be lower for children that have sustained a non-accidental head trauma (Oluigbo et al., 2012).

Anterior frontal space occupying lesions treated with a supraciliary “keyhole” small craniotomy were retrospectively analyzed (Benifla et al., 2016). The researchers noted that with the exception of one patient who developed a recurring post-surgical epidural hematoma, there were no major operative or post-operative complications. In a separate study by Matsuo and colleagues (2016), patients with a chronic subdural hematoma or a subdural hygroma underwent a burr-hole craniotomy without continuous drainage. It was reported that the majority of patients presented with bilateral chronic subdural hematoma or a subdural hygroma (17 out of 25), and with the exception of 5 patients where chronic subdural hematoma or subdural hygroma re-occurred, no complications were reported.

Conclusions

There is level 4 evidence that a decompressive craniectomy may improve intracranial pressure and cerebral perfusion pressure in pediatric patients post TBI.

There is level 1b evidence that a decompressive craniectomy is as effective as standard intracranial pressure management at reducing intracranial pressure in pediatric patients post TBI.

There is level 4 evidence that a late decompressive craniectomy (< 2hr post admission) and intraoperative blood loss (>300 mL) are associated with greater mortality and worse outcomes in pediatric patients undergoing this procedure post TBI.

There is level 4 evidence that children with a severe TBI are at risk of secondary complications following a decompressive craniectomy that may prolong rehabilitation.

There is level 4 evidence that patients who undergo a decompressive craniectomy have greater Glasgow Outcome Scale scores than pediatric patients with TBI who do not.

There is level 3 evidence that children who sustain a severe TBI from non-accidental trauma have poorer outcomes and higher odds of mortality following a decompressive craniectomy, when compared to accidental trauma victims.

There is level 4 evidence that supraciliary “keyhole” small craniotomies for the treatment of anterior frontal space occupying lesions are not associated with major operative or post-operative complications in pediatric patients post ABI.

There is level 4 evidence that a burr-hole craniotomy without continuous drainage for the treatment of either a chronic subdural hematoma or a subdural hygroma is not associated with complications in pediatric patients post ABI.

14.1.4 Pediatric Specific Care

Key Points

There may be no difference in mortality between pediatric TBI patients who sustained a penetrating injury and were treated at either an adult or pediatric trauma center.

Previous studies have reported conflicting evidence when comparing outcomes (i.e., mortality) of pediatric patients depending on whether they received treatment at an adult, or pediatric specific trauma center (Ochoa et al., 2007; Stelfox et al., 2010; Stylianos & Nathens, 2007). When compared to adult populations, pediatric patients vary greatly in their physiology and anatomy. As a result of this variability, pediatric patients who receive treatment from a pediatric-specific center may have better outcomes than those treated at adult trauma centres (Matsushima et al., 2012; Sathya et al., 2015; Walther et al., 2014). However,  in remote communities adult trauma centers may be the only or easiest way to access care, given then urgent nature of TBIs (Miyata et al., 2017). To investigate this, one study examined outcome measures of pediatric patients in center-specific care for the acute management of pediatric TBI.

Discussion

A single study was reviewed analyzing the difference in outcomes for patients treated a pediatric trauma center compared to those treated at an adult trauma center (Miyata et al., 2017). After reviewing outcomes for close to 27,000 patients, the researchers found no significant difference in mortality between patients who were treated at an adult or pediatric trauma center. However, it was found that children who sustained gunshot wounds, were under 12 yr of age, and underwent emergency operations at pediatric trauma centers were more likely to be discharged home. Although this study draws from an extremely large sample, there is an uneven split between the two treatment groups. Future studies with a more even distribution between groups are required to further analyze outcomes in patients post TBI.

Conclusions

There is level 3 evidence that there may be no difference in mortality between pediatric patients post TBI who were treated either at an adult or pediatric trauma center.

14.2 Post Traumatic Seizures

Key Points

Prophylactic phenytoin likely does not reduce early (< 1 week post injury) or late (>1 week post injury) seizures in children post ABI.

Patients receiving prophylactic levetiracetam may be more likely to develop post traumatic seizures if they are younger and have experienced abusive head trauma.

Post traumatic seizures (PTS) are one the most common complications in adults and children following ABI (Rumalla et al., 2018). Risk factors for PTS include severe TBI, abusive head trauma, and younger age (<2 years) (Arndt et al., 2013; Liesemer et al., 2011; O’Neill et al., 2015). However, several observational studies have shown that PTS are associated with increased mortality and poorer functional outcomes in the pediatric population (Keret et al., 2017); (Pearl et al., 2013); (Ruzas et al., 2017). In addition, children differ from adults in terms of mechanism of injury and pathophysiology leading to the development of PTS.  PTS are classified as occuring immediately (within 24 hours), early (within a week) or late (within a month). It is thought that PTS may contribute to secondary brain injury in children through severeal mechanisms including increased metabolic demands, cerebral edema, neuronal excitotoxicity, impaired blood supply and elevated ICP (Chung & O’Brien, 2016); (Hale et al., 2018). However, pediatric ABI is associated with greater volumes of post traumatic edema as compared to adults (Aldrich et al., 1992). This may affect the development of PTS as intracerebral fluid deposition is thought to mediate pathogenesis of both early and late PTS (Willmore, 1990).

The incidence of early PTS in children has been reported to be between 12-18% (Liesemer et al., 2011; Rumalla et al., 2018; Thapa et al., 2010), although subclinical epileptiform activity has been detected with continuous EEG monitoring in up to 42.5% of children with head trauma (Arndt et al., 2013). The presence of PTS may be an early warning sign for developing post traumatic epilepsy (PTE). In one retrospective cohort study, children with moderate to severe TBI were found to have an increased risk of PTE (Keret et al., 2018). ProphylacticIn adults, prophylactic anticonvulsants have proved effective in reducing early PTS. Although, the existing evidence for the treatment of PTS in the pediatric population is relatively scarce and consists of a handful of studies. As such, prophylactic anticonvulsants are only administered to children at some institutions and the indications and protocols vary significantly (Rumalla et al., 2018). In this sense, further research is necessary to determine the safety and efficacy of pharmacological prophylaxis in the treatment of PTS.

Discussion

Phenytoin prophylaxis was ineffective at preventing both early PTS (<1 wk of injury) (Young et al., 2004) and late PTS (>1 wk of injury) (Young et al., 1983) compared to placebo controls. However, there was an overall lower occurrence of PTS (6%) than what is reported in much of the PTS literature, according to the authors, which may have confounded the results (Young et al., 2004). Notably, there was also no difference observed in survival outcomes between phenytoin and placebo groups (Young et al., 2004).

Using a different anti-seizure agent, levetiracetam, PTS was found to occur in 17.6-25% of the study population despite pharmaceutical prophylaxis (Chung & O’Brien, 2016; Vaewpanich & Reuter-Rice, 2016). Children that developed early PTS after levetiracetam prophylaxis were younger and had experienced abusive head trauma, compared to those that did not develop PTS (Chung & O’Brien, 2016; Vaewpanich & Reuter-Rice, 2016). Although lacking a comparison group, Chung and O’Brien (2016) report that the prevalence of PTS (17.6%) post-levetiracetam administration is similar to prior studies without any seizure prophylaxis. Due to the lack of randomization and a proper control population, further studies are suggested to fully investigate the effect of levetiracetam prophylaxis in preventing PTS.

Conclusions

There is level 1b evidence that phenytoin prophylaxis may not reduce the occurrence of early (<1 week post injury) or late (>1 week post injury) post traumatic seizures compared to placebo in children post TBI.

There is level 4 evidence that children who develop early post traumatic seizures while receiving levetiracetam prophylaxis are younger and have experienced abusive head trauma, compared to those that did not develop post traumatic seizures.

14.3 Dysphagia, Feeding, and Nutrition

Key Points

Enhanced immune enteral feeding formulas may not be superior to regular formulas in regards to improving caloric and protein intake, however, may have beneficial anti-inflammatory properties.

Initiating nutritional support earlier may result in a decrease in mortality and better outcomes in a pediatric population post ABI.

Similarly to adults, children post ABI are commonly affected by swallowing problems (dysphagia), with the incidence ranging from 68-76% after a severe TBI (Morgan, 2010); (Popernack et al., 2015; Redmond & Lipp, 2006). Impaired oral motor skills often compromise oral intake leading to nutritional deficiencies (Morgan, 2010);(Popernack et al., 2015). This is problematic as children already have difficulty meeting their metabolic demands (Morgan, 2010). In order to facilitate optimal nutrition, a multidisciplinary approach is essential (Mei et al., 2018). The expertise of dietitians, occupational therapists and speech-language pathologists, as well as medical staff should be implemented (Mei et al., 2018). Moreover, nutrient intake should focus on decreasing unnecessary losses of lean body mass and promoting strength/endurance for rehabilitation through optimal caloric and protein intake (Malakouti et al., 2012; Redmond & Lipp, 2006).

The first step in rehabilitation is to assess swallowing. The four stages of swallowing (oral prepaory, oral, pharyngeal and esophageal) must work together to properly transition a bolus of food without airway aspiration (Popernack et al., 2015). If aspiration occurs, a variety of pulmonary issues may arise, such as pneumonia or wheezing with respiratory compromise (Popernack et al., 2015). Evaluations should be completed once the child is alert enough to eat and if the initial bedside assessment identifies a need to proceed with further investigation, videoflouroscopy may be performed. Using this technique, pharyngeal or oral deficits in the transit of a food bolus or fluids may be identified (Morgan et al., 2002; Popernack et al., 2015).

The results of the initial assessment determine therapeutic approaches to facilitate feeding assistance. These approaches may include modifying diet consistencies, using adaptive feeding devices, meal scheduling and increasing endurance for self-feeding (Redmond & Lipp, 2006). In patients who cannot swallow independently, parenteral or enteral nutritional assistance may be provided. Several systematic reviews have demonstrated that both feeding mechanisms increase survival rates when introduced early (<48 hours) rather than late (>48 hours) (Perel et al., 2006); (Hadley et al., 1986); (Taylor et al., 1999). In particular, one systematic review found earlier feeding was significantly associated with lower mortality rates (0.67 [0.41-1.07]) compared to late feeding (0.75 [0.50-1.11]) (Perel et al., 2006).

Discussion

Early enteral administration of an immune enhanced formula (glutamine, arginine, antioxidants, and omega-3 fatty acids; Stresson) did not improve mean caloric and protein intake in children compared to modified regular feeding (Tentrini) (Briassoulis et al., 2006). Although not significant in the long-term, nitrogen balance, an important marker for metabolism, was greater for children receiving the immune enhanced formula within 24 hours. The authors attributed this increase to the presence of additional nitrogen in arginine and endogenous nitrogen growth due to the presence of arginine and glutamine (Briassoulis et al., 2006). Overall, immunonutrition was only beneficial to reduce cytokines, specifically interleukin-8, and early gastric colonization (Briassoulis et al., 2006).

In a series of case studies, food texture was found to affect the amount of food consumed by children following a severe ABI (DeMatteo et al., 2002), which as mentioned earlier, is important to regulate in order to reach the enhanced metabolic demands. Soft textures were the most difficult to take in and swallowing efficacy between minced and pureed foods varied between children (N=3) (DeMatteo et al., 2002). Additionally, the person administering the food had a significant effect on the child’s food intake, therefore the authors discussed the importance of individualized treatment plans for feeding in children following a severe ABI (DeMatteo et al., 2002).

In a secondary RCT analysis of a hypothermia treatment trial, Meinert and colleagues (2018) examined nutritional support in children post ABI. The authors stratified individuals into 4 groups corresponding to the onset of their nutritional support received: no support, nutritional support initiated <48 hours, between 48 and 72 hours, and support initiated 72 to 168 hours after injury (Meinert et al., 2018). The authors found a significant main effect of treatment group on mortality and Glasgow Extended Outcomes, with earlier nutritional support having better outcomes (Meinert et al., 2018).

Conclusions

There is level 1b evidence that the administration of enhanced immune formulas may not be superior to regular formulas in regards to increasing caloric and protein intake in children post TBI.

There is level 1b evidence that enhanced immune formulas may be superior to regular formulas at reducing markers of infection and inflammation (interleukin-8 concentrations and early gastric colonization) and improving 24 hour nitrogen balance in children post TBI.

There is level 1b evidence that initiating nutritional support earlier after ABI results in a decrease in mortality and better outcomes.

14.4 Rehabilitation

14.4.1 Behavioural Interventions

In adult and pediatric populations TBI can result in several negative outcomes including cognitive and behavioural impairments. In particular, one behavioural impairment commonly experienced is agitation, with 8-70% of patients recovering from severe TBI reporting having experienced it (Wolffbrandt et al., 2013). Although agitation has not been defined consistently, it is commonly described as behavioural excess that occurs during altered states of consciousness (Nowicki et al., 2019). There are several common clinical characteristics that are reported across the literature including: aggression, restlessness, disinhibition and emotional lability (Gerring et al., 2009; Nowicki et al., 2019; Sohlberg, 2001). Additionally, following a TBI, children are at a greater risk for developing internalizing behaviours, such as anxiety, depression, and personality changes (Li & Liu, 2013). Often, these behaviours occur during the critical stages of rehabilitation, interrupting rehabilitation and education goals (Gurdin et al., 2005).

Despite what is known about the prevalence of agitation post TBI, the literature regarding methods to address the issue is limited. The behaviour therapies that have been evaluated in pediatric TBI populations can be grouped into five categories: cognitive and behavioural therapies, combinational or comparative studies examining behavioural therapies, family based behavioural therapy, community interventions for behavioural therapy, and social re-integration. These topics are explored below.

14.4.1.1 Cognitive and Behavioural Therapies

Key Points

Cognitive behavioural therapy may reduce internalizing behaviour disorders and improve socialization in pediatric patients post ABI, especially in patients not receiving adjunct pharmacotherapy.

Self-monitoring training might improve on-task behaviour, but not accuracy in completing assignments or task engagement, in pediatric patients post TBI.

Behavioural therapies might reduce problematic behaviours, lower agitation, and increase autonomy in pediatric patients post ABI.

Behavioural therapies are directed at reducing or eliminating problematic behaviours through the application of behavioural and social learning principles. These treatments involve identifying behaviours and relevant stimulus cues to implement reinforcement strategies, which establish appropriate behaviours. Once adequate behavioural control is established, external “behavioural control” cues and contingencies can eventually be reduced or withdrawn with maintenance of the desired behaviours.

Different behavioural profiles are typically seen at different stages of injury. For example, early behavioural consequences often include restlessness and agitation associated with confusion and disorientation. As recovery continues, problems with impulse control, cooperation with treatment activities and appropriate social interactions may emerge. Challenging behaviors have been related to both neurological (e.g. injury severity) and interpersonal (e.g., coping skills) factors, and several models have been put forward to describe the various influences on behavioral difficulties following ABI (Prigatano, 1992; Sbordone, 1990). Continued problematic behavior in children and adolescents after brain trauma is a major barrier to medical care, rehabilitation, and eventual independent living (Gerring et al., 2009).

In their review of psychological interventions in children with ABI, Warschausky et al., (1999) indicated that most of the literature on behavioural therapies in children with ABI has focused on externalizing features (e.g., aggression, disruptive behaviours) but that few studies had involved rigorous evaluation of specific interventions. These authors concluded that behavioural therapies in this population appear promising but are in need of further empirical support. It appears that operant conditioning paradigms for decreasing aggressive behaviours have been successful, although there are inconsistent reports of maintenance of gains.

Discussion

Cognitive behavioral therapy improved adaptive behaviour and reduced dysfunctional behaviours such an anxiety, depression, and internalizing behaviours in children who sustained a severe TBI (Pastore et al., 2011). Furthermore, children with greater behavioural impairments at baseline improved the most in the “parental ratings of behaviour” section of the Child Behaviour Checklist. In children not receiving adjunct pharmacotherapy, CBT facilitated adequate social reintegration following a severe TBI. This group significantly improved on all Child Behaviour Checklist parameters, as well as the VABS socialization scale when compared to those receiving additional pharmacotherapy (Pastore et al., 2011).

An earlier method of evaluating a particular behavioural therapy was to compare pre- and post-intervention results for a small number of subjects (Pruneti et al., 1989; Slifer et al., 1993; Slifer et al., 1995; Slifer et al., 1997). One of these studies introduced patients to different self-monitoring techniques to monitor their own productivity, attention, and accuracy in completing math assignments (Selznick & Savage, 2000). After a withdrawal period where patients were asked to self-monitor if they chose to, researchers found a significant increase in on-task behavior for all 3 subjects—improvements which were sustained on follow-up for the two patients whose data was available. It is important to note both accuracy in completing assignments and task engagement remained variable. The remaining studies implemented some form of compliance training protocol utilizing operant conditioning techniques such as positive reinforcement following social and cooperative behaviour, planned ignoring for disruptive behaviour, and a loss of reward for aggressive behaviour (Pruneti et al., 1989; Slifer et al., 1993; Slifer et al., 1995; Slifer et al., 1997). Compliance training was found to be successful in lowering agitation ranting scale scores (Slifer et al., 1997), occurrence of negative behaviours (Pruneti et al., 1989; Slifer et al., 1993; Slifer et al., 1995; Slifer et al., 1997), and greater level of autonomy (Pruneti et al., 1989). While all of the studies reviewed reported at least short-term gains in behaviour management following the interventions, the majority of these studies were uncontrolled multiple case reports. Moreover, in many of the multiple-case studies, subjects were not matched on many seemingly important variables, such as age, IQ, extent of cognitive deficits, or concurrent medication use.

An important variable that differs widely across studies is the time since injury.  This is important because, as previously mentioned, different behavioural problems may appear at different stages of recovery. For example, Slifer and colleagues (1993; 1995; 1997) have focused on the very early stages of recovery, during the post-traumatic amnesia phase, whereas other researchers have studied children or adolescents years after a brain injury (Glang et al., 1997; Selznick & Savage, 2000).

Conclusions

There is level 2 evidence that cognitive behavioral therapy may reduce anxiety, depression, and internalizing behaviour compared to no therapy in pediatric patients post ABI.

There is level 2 evidence that cognitive behavioural therapy may be more effective at improving socialization and internalizing behaviour in children post ABI who are not receiving adjunct pharmacotherapy, compared to those who are.

There is level 4 evidence that self-monitoring training can improve on-task behaviour, but not accuracy in completing assignments or task engagement, in children post TBI.

There is level 4 evidence that behavioural therapies for children with ABI may be effective in reducing or eliminating problematic behaviours, lowering agitation, and increasing autonomy.

14.4.1.2 Combination or Comparative studies

Key Points

Counselor-assisted problem-solving and internet resource interventions may be effective at mitigating behavioural problems in pediatric patients post TBI, however, conflicting evidence exists as to which is superior and who benefits the most.

Mental health services are commonly underutilized within the first two years of a TBI, regardless of treatment (counsellor-assisted problem-solving versus internet resource comparison), gender, race, age, or socioeconomic status.

The following studies investigate the effect of combinational behavioural therapies, or compare different behavioural therapies to examine their relative efficacy in treating behavioral disorders in pediatric patients post ABI.

Discussion

Four studies compared the effects of an online problem solving intervention program (CAPS) to an internet resource intervention (IRC) administered to adolescents within the first year following a moderate TBI, in hopes of remediating refractory behavioural problems (Wade et al., 2014b; Wade et al., 2015b; Wade et al., 2011). The CAPS intervention was found to improve parental ratings of externalizing, but not internalizing behaviours (such as anxiety and depression) in children compared to the IRC group (Wade et al., 2014b). Different results were found by Tlustos and colleagues (2016), as they noted inter-group differences only in social behavioural (HCSBS scores) and in specific subpopulations: younger teens with moderate injuries and older teens with severe injuries. Conflict between parents and adolescents was significantly reduced following training in the CAPS group compared to the IRC group, which may lead to additional behavioural improvements over time (Wade et al., 2011). Adolescents with low socioeconomic status and greater injury severity were more susceptible to initial behavioural problems following injury, however, this subset of adolescents received the greatest benefit from the CAPS intervention (Wade et al., 2011). Interestingly, different results were reported by Tlustos et al. (2016) as it was found that patients with TBI of higher socioeconomic status had higher scores on measures of behavioural and social competence after treatment. Similarly, children who had more externalizing behaviours prior to the intervention reported significant reduction in externalizing behaviours post-intervention (Wade et al., 2015b).

A secondary analysis of the study by Tlustos et al. (2016) was recently conducted with the aim of analysing patient use of mental health services post injury (Huebner et al., 2017). While it was reported that only 30% of patients utilized mental health services in a 2-year period following TBI, there were no differences between treatment group (CAPS versus IRC), gender, race, age, or socioeconomic status in terms of service usage.

Problem solving training is important for teaching coping skills that will lead to situational adaptations and improvements in behavioural competence, which can reduce or prevent the negative effects of stress that are prominent following a TBI (Wade et al., 2014b).

Conclusions

There is conflicting (level 1b) evidence as to whether a counsellor-assisted problem-solving (CAPS) group is superior to an internet resource comparison intervention at improving management of externalizing, internalizing, and socialization behaviours in pediatric patients post TBI.

There is level 1b evidence that a counsellor-assisted problem-solving program may be superior to an internet resource comparison intervention at reducing conflict between parents and adolescents post TBI.

There is conflicting (level 1b) evidence as to whether lower or higher socioeconomic patients benefit most from a counsellor-assisted problem-solving intervention compared to an internet resource intervention post TBI.

There is level 1b evidence that treatment (counsellor-assisted problem-solving versus internet resource comparison), gender, race, age, or socioeconomic status do not affect use of mental health services in pediatric patients post TBI. 

14.4.1.3 Family-Supported Interventions

Familial support plays a critical role in a child’s recovery and development following an ABI, as it has been demonstrated that family functioning is a significant moderator of outcomes following brain injury (Braga et al., 2005; Yeates & Taylor, 2005). This is particularly significant given that increases in family dysfunction following pediatric ABI have been well-documented (Cole et al., 2009). Families play a critical role throughout the acute and post-acute stages of recovery (Savage et al., 2005). It is thought that family-centered interventions help to improve parental, child and sibling adaptation following injury (Wade et al., 2006b). It has been noted that families take on four unique roles in a child’s recovery from brain injury: (1) as observers of the child’s care, (2) as experts with insightful pre- and post-injury information regarding the child’s abilities, (3) as communicators with professional caregivers and (4) as advocates for the child (Savage et al., 2005).

Unfortunately, being the parent of a child with an ABI can be a demanding and stressful experience. For example, Brown et al. (2013) demonstrated that following a child’s ABI, parents experience feelings of isolation, distress, relationship discord, anxiety, and engage in negative coping mechanisms such as avoidance and disengagment behaviours. In addition, parental psychiatric symptoms can impact the childs recovery. One study showed that children of parents who demonstraetd internalizing issues were more likely to demonstrate internalizing issues of their own following an ABI (postitive correlation of 22-26%) (Peterson et al., 2013). There is a bi-directional relationship between parent and child function; improvements in parental function are likely to have an effect on child adjustment and outcomes following an ABI and the reverse is also true (Taylor et al., 2001). Therefore it is important to target both child and parental outcomes for optimal recovery after a child has sustained a brain injury.

14.4.1.4 Web-Based Family-Supported Interventions

Key Points

Online parenting skills workshops may be superior to internet resources in acutely reducing caregiver stress, depression, or self-efficacy. However, such workshops are likely not effective at improving parent-child communication post ABI.

An online problem-solving program with therapist assistance may be superior to an internet resource comparison group at improving compliant behaviour and self-management in children post TBI.

Web-based teen problem solving intervention programs are effective in reducing parental depression, anxiety, and distress compared to an internet resource comparison group, especially in families with lower socioeconomic status.

Family-based interventions benefit children, adolescents, and their families following brain injury.

An app-based coaching intervention may be effective in raising confidence and participation in activities following a pediatric TBI or brain tumor.

Family based interventions delivered online have gained popularity due to easier accessibility to treatment. Families can access online treatment programs from their homes and teleconference with a therapist over the phone/internet (Narad et al., 2015). Online programs address many frequently identified barriers to care and treatment, such as time, and proximity of knowledgeable providers (Wade et al., 2006b). Online family supported interventions aim to not only improve child outcomes, but also parental outcomes and communication between family members.

Discussion

Therapy provided with the assistance of a counsellor (CAPS) was examined for a population of children (mean age >10 yr) whose ABI had occurred within the last year (Narad et al., 2015). Counsellor assistance to complete psychoeducational modules did not significantly improve family function (i.e., communication and transactions between family members), when compared to an internet resource comparison group (IRC) (Narad et al., 2015). However, children improved in self-management and compliant behaviours from pre- to post-treatment in the CAPS group when compared to the IRC group (Wade et al., 2006c). Upon analyzing parental outcomes post-intervention, parents in the treatment group had a reduction in depressive symptoms, anxiety, and distress, but not problem solving compared to the IRC (Wade et al., 2006b). The reduction in depressive symptoms was particularly evident when participants completed more than four sessions (Wade et al., 2014a). However, long term analysis (18 months post-intervention) revealed that online counsellor assisted therapy only reduced caregiver psychological distress, not depression or self-efficacy (Petranovich et al., 2015).

Some benefits from counsellor assisted online therapy were evident only for a subset of individuals. For example, parental self-efficacy improved only in non-frequent computer users (Wade et al., 2015a) and self-management improved for older children (>11yr) in the treatment arm compared to older children in the IRC (Wade et al., 2006b). Other benefits were found for individuals with severe versus moderate TBI, however, the effect sizes were small and reports were inconsistent between parents and adolescents (Narad et al., 2015).

An important moderating variable that was found within the counsellor assisted online therapy group was socioeconomic status (Petranovich et al., 2015; Wade et al., 2012). Parental distress levels were reduced for low income parents compared to those with high socioeconomic status, in the treatment group more so than for those in the IRC. Within both groups, low income parents reported significantly reduced depressive symptoms post-treatment. Among high income parents, the control group (IRC) reported reduced depressive symptoms post-treatment, whereas there was no significant difference observed in the online intervention group (Wade et al., 2012). Authors hypothesize that counsellor assisted therapy may be more beneficial for a subset of individual based on socioeconomic status and future research is warranted.

Online counsellor assisted therapy resulted in improved adolescent behavioural problems, parental depression and parent-child conflicts post-treatment (Wade et al., 2008). Additionally, there were improvements within intervention and IRC groups on several outcomes, such as the transactional family characteristics and effective communication (Narad et al., 2015), distress (Wade et al., 2014b), and depression (Petranovich et al., 2015). Although the differences between groups were not significant, the authors suggested that both interventions may be beneficial to reduce caregiver burden and family functioning post-ABI. Wade and colleagues  (2018a) a follow-up study on the TOPS therapy intervention and found that the family group scored significantly lower on scores of executive dysfunction compared to the other two groups, however, no other significant between-groups differences were noted.

Wade and colleagues (2018a) launched a Social Participation and Navigation app that administers a coaching intervention. Using this app, they conducted a pilot study with 12 pediatric TBI and brain tumor individuals. They found both groups were satisfied with the app and it was easy to use. In addition, they found an increase pre to post-assessment in confidence scores and participation frequency (Wade et al., 2018a).

An online parenting skills program, Internet-Based Interacting Together Everyday (I-InTERACT), instructed parents on the management of children post-ABI. I-InTERACT was compared to an IRC to determine the effects on caregiver strain and parent-child interactions (Antonini et al., 2014; Mast et al., 2014; Raj et al., 2015). The I-InTERACT parenting skills program did not reduce depression or stress, nor did it improve self-efficacy and distress levels (Raj et al., 2015). However, within this population, 92% of caregivers were mothers and therefore the results may not be representative of what changes could be seen in other caregivers such as fathers or grandparents (Raj et al., 2015). I-InTERACT treatment increased the frequency of positive parental statements and praise compared to the IRC group (Antonini et al., 2014). This improvement was also present in a subset of children that who sustained abusive head trauma (Mast et al., 2014). The number of sessions completed by families positively correlated with the frequency of positive parenting skills (Antonini et al., 2014). Other significant differences were evident upon sub-analyses of parental income. Parental distress was significantly reduced in low-income, but not high income, families following the I-InTERACT program compared to pre-intervention (Raj et al., 2015). Additionally, parental income predicted child’s behaviour following the intervention in that children from low-income families had a significant reduction in behavioural problems, which was not apparent in children from high-income families (Antonini et al., 2014). The authors performed a follow-up RCT on the I-InTERACT program, comparing it to an express model and a regular care group (Raj et al., 2018). The authors did not find any significant between-group differences from the regular program, the express model, and regular care on measures of caregiver depression, distress stress, and self-efficacy (Raj et al., 2018).

Conclusions

There is level 1b evidence that an online problem-solving program with therapist assistance may not be superior to an internet resource comparison group at improving parent-teen communications and conflict post ABI.

There is level 1a evidence that an online problem-solving program with therapist assistance may be superior to an internet resource comparison group at improving compliant behaviour and self-management in children post TBI.

There is level 1a evidence that an online problem-solving program with therapist assistance may be superior to an internet resource comparison group at acutely improving anxiety, depression, and distress in the parents of children post ABI; however, only improvements in distress may be present at 18 months.

There is level 1a evidence that lower socioeconomic status is associated with greater reductions in distress and depressive symptoms following counsellor-assisted online therapy when compared to higher socioeconomic status in parents of children post ABI.

There is level 2 evidence that online problem solving with audio support may not be superior to the same program without audio support with regards to improving adolescent behavioural issues and depression in children post TBI.

There is level 1b evidence that an online parenting skills workshops (I-InTERACT) may improve positive parental involvement with their child, when compared with an internet resource group, in children post TBI.

There is level 1b evidence that an online parenting skills program (I-InTERACT) may not be superior to an internet resource comparison group at improving caregiver stress, distress, depression, and self-efficacy in individuals caring for children post TBI.

There is level 4 evidence that an app-based coaching intervention may increase confidence and participation frequency in pediatric TBI and brain tumor individuals.

14.4.1.5 Alternative Family-Supported Interventions

Key Points

“Stepping Stone Triple P with Acceptance and Commitment Therapy” may improve parental outcomes and short-term behavioural problems in children post ABI.

Face to face family problem solving therapy may improve internalizing behavioural problems in children post TBI, however, it may not impact parental distress or relationship satisfaction.

Family based rehabilitation might be superior to clinician-directed care to improve cognitive and physical outcomes in children following a TBI.

A family focused inpatient social work program may be just as effective as a usual care intervention in reducing feelings of trauma and grief in parents/caregivers of children post-TBI. However, parents/caregivers undergoing an inpatient social work program may report increased confidence in managing pediatric TBI and feelings of more supportive counselling, increased family resources, and awareness of medical issues than a usual care intervention.

A few non-web-based interventions have been evaluated for families of children that have sustained an ABI. Contrary to web-based programs, face to face interventions can provide social support for parents through the rehabilitation process (Brown & Whittingham, 2015). However, similarly to web-based interventions the main focus of therapy continues to be on family dynamics and improving long term outcomes in families with a child that has sustained an ABI.

 

Discussion

The Stepping Stone Triple P and Acceptance and Commitment Therapy (ACT+SST) combined programs aim to improve family outcomes and communication within families with a child who suffered an ABI (Karver et al., 2014; Narad et al., 2015). Behavioural problems were reduced in children who underwent the intervention, however, they were not maintained by the 6 month follow-up (Karver et al., 2014). Both cumulative and delayed deficits are possible following a brain injury, which may lead to long term clinical deterioration post ABI. Thus, the authors hypothesize these children may have experienced such a phenomenon and perhaps maintaining interventions for longer time periods may be more beneficial (the presented study treatment lasted 10 weeks) (Karver et al., 2014). In terms of parental outcomes, confidence, disagreements between couples, and psychological distress were significantly improved following the ACT + SSTP intervention (Narad et al., 2015). Such improvements were not found in the usual care control group, therefore results cannot be attributed to spontaneous recovery (Narad et al., 2015). No significant changes were found for parental relationship satisfaction or depression as both control and intervention groups had improved post-treatment (Narad et al., 2015).

A family problem solving therapy that was delivered face to face was compared to usual care to determine its effects on behavioural problems and parental outcomes following a pediatric ABI (Wade et al., 2006b). Children within one-year post-injury improved in behavioural outcomes following the family problem solving intervention when compared to children in the usual care group. Particularly, improvements were reported for internalizing and withdrawal behaviours, as well as depression and anxiety. However, parental distress did improve following therapy, which is contrary to other studies (Wade et al., 2006b). Rather than changes in parental distress influencing the child’s behaviour changes, the authors hypothesized that parental practices (which were reported in the satisfaction survey, such as better understanding of and relationship with their child) contributed to the magnitude of changes reported (Wade et al., 2006b).

Family rehabilitation consisting of home based activities improved both cognitive and physical abilities for children following a TBI, compared to standard clinician based therapy (Braga et al., 2005). Specifically, IQ, motor development, and functional independence were improved in children receiving the family rehabilitation. Parents were able to be effectively trained to deliver the intervention and this result was unrelated to parental education status. Therefore, children in the chronic phase of recovery (mean time post injury 1 year) can benefit from family driven rehabilitation at home that may be easily accepted and learned across families (Braga et al., 2005).

A study examining a dedicated ‘family forward’ social work program compared against a usual care population of children with TBI (Hickey et al., 2018b) looked specifically at the parents/caregivers experience (Hickey et al., 2018b). The authors first recruited for their usual care group, then recruited for the family forward program. This program involved family sessions each week that encouraged expression of grief responses to the child’s injury and a counselling process. The usual care intervention consisted of a typical social work program (Hickey et al., 2018a). The study authors found both groups saw reductions in trauma and grief responses but were not significantly different from one another (Hickey et al., 2018a). In a separate paper, on the family forward program the authors found a significant difference between groups on supportive counselling, family resources, and medical care issue, with the family forward group showing higher scores at inpatient discharge. (Hickey et al., 2018b). At 6-weeks post discharge, the authors found that the family forward group scored higher on management of the TBI condition (Hickey et al., 2018b). The authors found no differences between groups on general family functioning and psychosocial measures (Hickey et al., 2018b).

Conclusions

There is level 2 evidence that the Stepping Stone Triple P program combined with Acceptance and Commitment Therapy may be superior to usual care at improving behavioural problems up to 6 months in children post ABI.

There is level 2 evidence that the Stepping Stone Triple P program combined with Acceptance and Commitment Therapy may improve parental distress, confidence, psychological flexibility, and conflict, but not depression, when compared to usual care in children post ABI.

There is level 2 evidence that face to face family problem solving therapy may be superior to usual care in terms of reducing internalizing problems (depression and anxiety) in children post TBI, but not parental distress or relationship satisfaction.

There is level 2 evidence that family-based therapy may be superior to standard clinician-directed care for improving intelligence, motor development, and functional independence in children post TBI.

There is level 4 evidence that a family focused inpatient social work program for parents/caregivers after their child’s TBI may not significantly decrease feelings of trauma or grief any more than a usual care intervention.

There is level 4 evidence that a family focused inpatient social work program for parents/caregivers after their child’s TBI may increase parent/caregiver confidence in managing the condition and feelings of more supportive counselling, increased family resources, and awareness of medical issues than a usual care intervention.

14.4.1.6 Community-Based Interventions

Key Points

Use of community resource coordinators post discharge may not improve functional outcomes in children post TBI.

Multidisciplinary outpatient programs may improve functional outcomes for children following ABI.

Rehabilitation efforts provided in the community are often proposed as an attractive and cost-effective alternative to residential or hospital-based rehabilitation programs. Following hospital discharge, the school setting can only provide so much re-integrative rehabilitation due to the restricted and planned environment at school. Participation in community based programming reflects real world skill development, such as interactions with others, and can foster more transferable and appropriate interactions for children post-ABI (Agnihotri et al., 2010).

Discussion

Two studies, one RCT and one pre-post, evaluated the effectiveness of community based therapy for children following an ABI. The RCT used an intervention group that received a Community Resource Coordinator (CRC) post-discharge to facilitate compliance with medications and attend follow-up visits (Carney et al., 2016). Children who were connected with this community resource coordinator did not improve on functional outcomes (PCPC, PCOC categories of the Peds-QL) compared to a usual care control group by 6 months post-injury. However, children with superior family functioning, as measured by scores on the family impact subscale of the pediatric quality of life, had better functional outcomes than those with lower family functioning (Carney et al., 2016). This relationship was correlative and future research is needed to determine causality.

A pre-post study examined the effectiveness of intervention by a multidisciplinary, community-based team on general areas of functioning early (<6 wk) after a child sustained an ABI (Emanuelson et al., 2003). Motor function and aspects of functional communication and behaviour, but not neuropsychological outcomes, significantly improved by the 12 month follow-up mark (Emanuelson et al., 2003). More research is required with this population, as community-based rehabilitation could provide a support network for children and their families dealing with the impact of brain injury.

Conclusions

There is level 1b evidence that the allocation of community resource coordinators to a family post discharge may not be superior to standard care at improving functional outcomes in children following a TBI.

There is level 4 evidence that a multidisciplinary outpatient program may improve functional communication and behaviour, but not neuropsychological outcomes, in children post ABI.

14.4.1.7 Social Reintegration

Key Points

Online family problem solving interventions likely improve everyday functioning, specifically in the school and community domains, but not at home, in adolescents who have sustained a TBI.

Children with a physical disability or chronic condition may find it difficult to “fit in” with peers, as their care and needs are different than those of normally developing children of the same age. It has been suggested the children who have experienced head trauma may have even greater challenges, as they must often contend with dysfunctions of critical brain regions that enable normal social interaction (Lewis et al., 2000). Following a brain injury, the most detrimental long-lasting social consequences for children and adolescents are the loss of friends, the inability to participate in many social and leisure activities, and the absence of social support (Glang et al., 1997). Social networks are crucial to the psychological wellbeing of students, as those with social support are less likely to experience difficulties relating to depression, anxiety or other affective disorders. Returning to school can be a daunting prospect for a young student who has just recovered from TBI. Hawley (2012) reported that levels of self-esteem in children with a TBI at school were significantly lower than in controls and significantly lower than population based norms. Lower self-esteem in children with TBIs was also significantly associated with anxiety and depression.

A literature review by Mealings et al. (2012) on school re-entry revealed that students with a TBI found special accommodation/consideration, individual assistance, effective planning and a transition program as the most helpful methods of reintegrating back into school. Conversely, lack of understanding and awareness of TBI, and not receiving help that had been planned were regarded as the most detrimental issues. While these methods suit an educational setting, there may be different requirements in social environments.

Discussion

Glang and colleagues (2018) examined a hospital to school transition program for children with TBI that require special education or behavioural adjustments. This STEP program was designed to promote advocacy for TBI individuals and increase identification of a need for special education services (Glang et al., 2018). The authors did not find any significant difference between the STEP program participants and the usual care group on any of their measures, specifically the child behaviour checklist (CBCL) (Glang et al., 2018).

Wade et al. (2015b) utilized an online family program for problem solving therapy to elicit long-term improvements for adolescents an average of 3 months post-TBI. Adolescents in the intervention group improved in their everyday and community function at 12 months, but not in their home function, compared to a control group (Wade et al., 2015b). Such improvements were not apparent until 12 months and were not seen at the 18 moth follow up. The authors suggest that changes in problem solving and executive function resulting from the intervention may take time to translate to improvements in everyday functioning (Wade et al., 2015b). Improvements in school/work and community functioning were significant and are important for re-integration for a child post-discharge (Wade et al., 2015b).

Glang et al. (1997) investigated the results of a program designed to increase social networks for three children post TBI. The model appeared beneficial as social contacts increased after the intervention, however, no lasting changes in social functioning were reported. The ability to participate in social networking during childhood and adolescence is an important issue and should be investigated further.  Indeed, social skills may be an important area for future focus given that social problems may be among the most significant and long-lasting sequelae of brain injury in children (Glang et al., 1997).

Conclusions

There is level 1b evidence that family based online problem-solving programs, when compared to an internet resource comparison group, may improve functioning in school and the community, but not at home, at 12 months in adolescents post TBI.

 There is level 4 evidence that interventions directed at strengthening the social interactions of children with brain injury may be temporarily beneficial.

There is level 2 evidence that a dedicated transitional hospital to school program does not demonstrate any increased benefits than a usual care group for children post TBI.

14.4.1.8 Pharmacological Interventions

Key Points

Amantadine appears to be safe and efficacious in decreasing undesirable behaviours and improving the rate of recovery in children post TBI

Pharmacological interventions are often used  to treat aggressive or agitated behaviour post TBI in children and adults (Suskauer & Trovato, 2013). To date, no medication has proven to be effective in modifying outcomes in children with brain injury. However, investigators have studied the role of the psychostimulant methylphenidate and other dopamine enhancing medications, such as amantadine, for their effect on aggression and agitation post ABI.

As mentioned earlier in ‘Promoting Emergence from the Unconscious State’, amantadine is a non-competitive N-methyl-D-aspartate receptor antagonist. Currently, it is used for the treatment of neurological diseases such as Parkinson’s disease, neuroleptic side-effects  (dystonia, akinthesia) and neuroleptic malignant syndrome (Schneider et al., 1999). It is also thought to work pre- and post-synaptically to increase the amount of dopamine available in the synaptic cleft (Napolitano et al., 2005). The methodologial details and results from two studies investigating the use of amantadine for the treatment of behavioural disorders post pediatric TBI are listed in Table 14.16.

Discussion

Amantadine was determined to be safe to administer to children (Green et al., 2004). Although there were unfavourable side effects, such as aggression and nausea, these side effects remitted upon modification of dosage, cessation of amantadine treatment (Green et al., 2004) or persistence of treatment beyond 2 days (Beers et al., 2005).

In terms of efficacy, amantadine administration reduced the frequency of negative behaviours associated with frontal lobe injuries after 12 weeks of treatment (Beers et al., 2005). Subjective review of charts from observed behaviours in children (alertness, verbalizations, agitation) also improved, however, there were no comparator questions to help determine if such improvements were due to natural recovery or amantadine itself (Green et al., 2004). Although behaviours improved following amantadine treatment, cognitive function, post-traumatic amnesia, and hospital LOS did not (Beers et al., 2005). As such, the results must be interpreted with caution, due to lack of blinding between conditions and lack of comparators. Future placebo-controlled trials are warranted to determine the efficacy of amantadine to reduce negative behaviours in children following a TBI (Beers et al., 2005).

Conclusions

There is level 2 evidence that the use of amantadine can decrease the amount of aberrant behaviours, but may not improve cognitive functioning and problem solving, compared to usual care among children with a TBI.

There is level 3 evidence that amantadine is safe to administer in children following a TBI and facilitates rate of recovery, but not post-traumatic amnesia or hospital length of stay, post pediatric TBI.

14.4.2 Cognitive Therapies

In addition to behavioural problems, childhood ABI is associated with significant cognitive sequelae (Taylor et al., 2002; Yeates et al., 2002). Common cognitive consequences of childhood ABI include deficits in attention, memory, problem-solving, communication, decreased speed of information processing, and academic difficulties (Sohlberg, 2001).

Generally, communication skills in children with moderate to severe TBIs are more affected  than those with a mild TBI (Rivara et al., 2011). For example, Rivara et al. (2011) found that children with mild cognitive impairments faired better when communication scores were measured at 3 and 9 months post injury (Rivara et al., 2011). In terms of remediating communication skills, younger children benefit more from behaviour-based approaches whereas older adolescents benefit from reasoning strategies (Shaw, 2016). Compensatory assistance in an academic setting can reduce the cognitive demands of reading and writing. Examples of compensatory assistance tools include audiobooks, text-to-speech and speech-to-text software, educational assistants, and proof-reading programs. Interdisciplinary support such as ophthalmology, audiology, sleep management and pain management services can help to address cognitive-communicative disorders (Krause et al., 2015).

Cognitive therapies encompass a variety of interventions designed to help individuals with brain injury improve upon or compensate for cognitive deficits. There is a substantial body of research investigating the effectiveness of different rehabilitation techniques for remediating or compensating for cognitive deficits following brain injury in adults. However, research on the effectiveness of cognitive rehabilitation for the paediatric population is lacking.

14.4.2.1 Rehabilitation of Attentional Deficits

Following a brain injury, children often experience attentional deficits that require rehabilitation, however, determining the efficacy of rehabilitation is complicated by a number of factors. Firstly, there is no consensus regarding the definition of attention. In some cases, it is defined as a general construct, whereas in others it is defined as more specific sub-components of functioning (e.g. sustained, divided, focused or selective attention and, vigilance, or speed of information processing, etc). Secondly, interventions targeting attentional deficits have applied testing inconsistently, whereby the same tests are used to measure different aspects of attention. In addition, the same outcome measures are often used repeatedly, in turn confounding practice and treatment effects (e.g. if individuals are repeatedly exposed to PASAT performance testing, their scores improve significantly, biasing the results). Lastly, it appears as though many studies do not account for the rate of spontaneous recovery following brain injury, whereby the recovery of function occurs naturally in the absence of treatment (Welch-West et al., 2013).

14.4.2.1.1 Non-Pharmacological Interventions

Key Points

The Amsterdam Memory and Training program may improve selective, but not sustained attention in pediatric patients post ABI.

The Attention Improvement and Management (AIM) program may improve sustained, but not selective, attention skills in pediatric patients with TBI compared to healthy controls.

Attention-specific neuropsychological training improves cognition, attention and behavioral skills in pediatric patients post TBI.

A cognitive computerized training (CCT) program may be feasible for pediatric patients post TBI.

There is currently a scarcity of interventions available to target the rehabilitation of attention in children that have sustained an ABI. As previously mentioned, attention is difficult to assess and is a multifaceted construct. However, attentional deficits in children can be detrimental to proper academic, social, and psychological function (Park et al. 2009). Therefore, it is imperative to determine effective interventions to target attentional deficits.

Amsterdam Memory and Attention Training for Children

Despite the scarcity of interventions targeting the improvement of attention in children post ABI, one intervention has been established as a popular and reliable tool for improving deficits in this field. The Amsterdam Memory and Attention Training for Children (AMAT-c), originally developed for the treatment of attention deficits in children after cancer treatment, is used for the rehabilitation of cognitive impairments in children post ABI (Catroppa et al., 2015; Dvorak & van Heugten, 2018; van’t Hooft et al., 2003). The intervention consists of 3 phases, each targeting sustained attention, selective attention, or mental tracking, respectively. As the child progresses through the program, they complete increasingly difficult assignments and games with the assistance of a coach (Catroppa et al., 2015; Dvorak & van Heugten, 2018) . After initial successes were reported in children post ABI, the AMAT-c gained traction as one of the few interventions available that could improve cognitive outcomes in this vulnerable population. Studies evaluating the efficacy of AMAT-c on cognitive outcomes in a pediatric population post ABI are reviewed below.

Other Attention-Focused Interventions

While the AMAT-c program is the most commonly used intervention for improving cognitive deficiencies in children post ABI, other programs and interventions exist. The following studies analyzed the efficacy of non AMAT-c interventions on improving attention in children post ABI.

Discussion

Four studies evaluated the effectiveness of the Amsterdam Memory and Training for children (AMAT-c) intervention in children post ABI (Catroppa et al., 2015); (van’t Hooft et al., 2003); (Hooft et al., 2005). Three important aspects of cognitive function were evaluated in all four studies: sustained attention, selective attention, and memory. Several studies found no improvement in sustained attention among those children in the AMAT-c group when compared to baseline or to an interactive control group (Hooft et al., 2005; van ‘t Hooft et al., 2007). However, in a study with three participants, van’t Hooft et al. (2003) reported that sustained attention improved in all participants following AMAT-c. The results of the intervention on patient’s selective attention was conflicting. Three studies (2 RCTs and a case series) reported that selective attention improved in the AMAT-c intervention (Hooft et al., 2005; van’t Hooft et al., 2003) and that this improvement was maintained at 6 month follow-up (van ‘t Hooft et al., 2007). While one pre-post study reported that selective attention did not improve following treatment (Catroppa et al., 2015). The third outcome measured by the AMAT-c, memory, was improved in all studies, with certain specific aspects of memory improving more than others.

Treble-Barna et al. (2016) used a computerized program to administer the Attention Improvement and Management (AIM) program in adolescents in the chronic phase of TBI recovery. Patients that received the intervention improved in sustained, but not selective attention compared to healthy controls. However, there was no follow-up to determine the long-term effects of such intervention on attention. Another intervention used attention and neurological training for adolescents an average of 7-9 months post-injury (Galbiati et al., 2009). Adolescents in the intervention significantly improved their cognitive performance, attention skills, and adaptive behavioural skills compared to patients in the control group. The authors concluded that improvements in attention positively influenced everyday adaptive behaviours (Galbiati et al., 2009). In a feasibility study of a computerized cognitive training (CCT) program (LumosityTM) the authors used a stepped wedge randomized design to administer 8 weeks of the CCT (Corti et al., 2018). The CCT program did not only focus on attention, but had tasks pertaining to memory and executive functioning as well (Corti et al., 2018). The authors had nearly full completion (31 out of 32 participants) of required training programs as well as completion of 8 other feasibility criteria, and found that their Lumosity Performance Index (LPI) increased significantly from baseline to post-therapy. The LPI should be taken with caution, as it is a non-standardized measure of cognitive performance being directly related to the CCT program and was found to have a minimally significant correlation to full scale IQ (Corti et al., 2018).

Conclusions

There is level 1b evidence that the Amsterdam Memory and Training for children program may not improve sustained attention in pediatric patients post ABI compared an interactive program.

There is level 1b evidence that the Amsterdam Memory and Training for children may improve selective attention compared to an interactive program in pediatric patients post ABI.

There is level 2 evidence that the Attention Improvement and Management (AIM) program may improve sustained, but not selective, attention compared to healthy controls in children post TBI.

There is level 2 evidence that attention-specific neuropsychological training may improve attention compared to no training in pediatric patients post TBI.

There is level 2 evidence that a cognitive computerized training (CCT) program is feasible for use within a pediatric TBI population.

14.4.2.1.2 Pharmacological Interventions

Key Points

Evidence regarding the efficacy of methylphenidate in improving cognitive and behavioural function following pediatric TBI is conflicting.

Methylphenidate

Pharmacotherapy is a viable treatment option for children with attention deficits post-ABI. Methylphenidate (Ritalin) is a psychomotor stimulant, often used in the treatment of attention deficit/hyperactivity disorder (ADHD) in children, however, it can also be used to improve attention in children who have sustained a brain injury. It is believed that children with ADHD share some similar characteristics to children with ABI including: attention deficits, hyperactivity and impulsivity (Leonard et al., 2004). Specifically, methylphenidate has been shown to improve memory and attention in those with ADHD (Kempton et al., 1999). As such, methylphenidate has been implicated for use in the treatment of attention deficit disorders as a result of ABI.

Discussion

The literature regarding the effect of methylphenidate on the cognition of children post-TBI is conflicting. One RCT found improvement in all measures of cognition and attention (Mahalick et al., 1998), whereas another RCT found no improvements in behaviour, memory, speed of processing, or attention following methylphenidate treatment (Williams et al., 1998). Both RCTs utilized a placebo comparison group with a cross-over design, however, other methodological differences may have contributed to the conflicting findings. Mahalick et al. (1998) administered methylphenidate for all children at a set dosage of 0.3mg/kg, whereas Williams et al. (1998) administered a standard dose based on body weight category (i.e., <20kg, 21-29kg, >30kg). Furthermore, Mahalick et al. (1998) administered methylphenidate for 2 weeks, whereas Williams et al. (1998) treated for only 4 days, with a 3 day washout period between weeks. Further, Williams et al. (1998) included children who varied greatly in time post injury. Six subjects were within the first two years post injury when rapid changes in cognition are more likely and four were more than two years post injury. Given the difficulties in determining the extent of injury (mild versus severe), the differences in the length of time since injury, and the small sample size, the results of this study should be interpreted with caution (Williams et al., 1998).

The findings of Hornyak et al., (1997), suggest that the introduction of methylphenidate (unreported dosing) resulted in improved cognitive and behavioural function in children post TBI. These improvements were associated with increased participation in therapy at school and improvements in behaviours at home (Hornyak et al., 1997). Further corroborating those findings, a recent pre-post test noted that immediate-release methylphenidate improved disruptive behaviour at home and at school, and was associated with either no or few side effects in TBI and ADHD patients (Ekinci et al., 2017). Finally, Nikles et al. (2014) found that stimulants (methylphenidate or dexamphetamine) had a small effect on improvement of ADHD symptoms, such as attention and concentration. Although reported as an improvement, the difference compared to the placebo phase was not statistically significant (Nikles et al., 2014). Additionally, only children with ADHD-like behaviours were analyzed, which is a small subset of the overall TBI population, limiting generalizability. Future RCTs are needed to determine the effectiveness of methylphenidate on attention for pediatric TBI.

Conclusions

There is conflicting (level 1b) evidence regarding whether or not methylphenidate improves cognitive behavioural function compared to placebo in children following a TBI.

14.4.2.2 Rehabilitation of Learning and Memory

Key Points

Utilization of a pager in adolescents post TBI may help improve memory.

Utilization of a diary in combination with self-instructional training might temporarily improve memory in children post TBI.

Cognitive rehabilitation can improve intellectual function for children following brain injury.

Memory impairment is one of the most debilitating symptoms following brain injury. Additionally, it is estimated that the time and cost of care would be reduced if effective medical treatments were found to improve memory (Hooft et al., 2005; McLean et al., 1991).

When evaluating intervention strategies to improve memory performance following brain injury, the literature indicates that there are two main approaches to rehabilitation (1) restoration/retraining of memory or (2) compensation. Compensation includes “training strategies or techniques that aim to circumvent any difficulty that arises as a result of the memory impairment.” (McLean et al., 1991). Compensatory techniques include internal aids, for example “mnemonic strategies that restructure information that is to be learned” (McLean et al., 1991). Individuals with lower working memory capacity post-TBI are at a greater risk of encountering academic difficulties (Krause et al., 2015). Various interventions are designed to address this concern and support the literacy skills of adolescents with a TBI. Reading interventions, such as flashcards and repeated oral readings, can improve word recognition in these patients. In addition, metacognitive strategies such as note-taking, focusing attention on new information, building referential relationships across texts, and ensuring that performance and goal attainment are monitored may also be associated with improvements in academic ability (Krause et al., 2015).

Discussion

Several different interventions to rehabilitate memory and learning post TBI have been evaluated. Memory aids are one intervention tool that may be used to compensate for memory deficits in children post TBI. Wilson et al. (2009) used a pager as a memory aid to help children remember and attain their everyday tasks more consistently. All participants improved in their percentage of targeted behaviours achieved throughout the day when using the pager. These improvements were maintained (to a slightly lesser degree) when the pager was removed (Wilson et al., 2009). Another memory aid that has been tested is the use of a diary, specifically  when used in combination with self-instructional training that focused on developing self-regulation and self-awareness skills (Ho et al., 2011). Children in this study experienced improvements in their daily memory deficits, however, unlike with the pager system, these improvements were not maintained at follow-up. Furthermore, the number of diary entries was significantly correlated with improvement in memory deficits. Conversely, Ho et al. (2011) report that memory impairments are associated with internalizing behaviours such as depression and anxiety.

Using a different approach, Melchers et al. (1999) used sensory stimulation while children were in a coma followed by cognitive neuropsychological rehabilitation upon awakening to remediate learning deficits post-TBI. Although only reporting preliminary results, the authors report that children had greater improvements in intellectual development, approaching age appropriate levels, one-year post-injury as compared to controls who further declined from pre-treatment levels. However, due to lack of equal distribution of injury severity between groups, the results may not be generalizable (Melchers et al., 1999).

In a case series completed by Brett and Laatsch (1998), 10 school aged children were offered biweekly session of cognitive rehabilitation for 20 weeks. Pre- and post-testing results revealed a modest improvement in memory skills only. This was attributed to engagement in a variety of verbal memory strategies (repetition, clustering, and semantic processing).

Conclusions

There is level 2 evidence that the use of a pager system may improve memory and planning activities compared to having no pager system in adolescents post TBI.

There is level 4 evidence that rehabilitation focused around diary entries and self-instructional training may temporarily improve memory deficits in children post TBI.

There is level 2 evidence that sensory stimulation paired with cognitive neuropsychological rehabilitation may improve intellectual development in children with severe TBI compared to controls.

There is level 4 evidence that biweekly sessions of cognitive rehabilitation may improve memory skills in pediatric patients post TBI.

14.4.2.3 Rehabilitation of Executive Functioning

Executive function refers to higher-level cognitive functions that are primarily mediated by the frontal lobe. These functions include: insight, awareness, judgment, planning, organization, problem solving, multi-tasking, and working memory (Lezak, 1983). Executive deficits are particularly relevant following TBI from both a pathophysiological as well as a psychosocial perspective. The frontal lobe is  frequently and bilaterally involved in TBI, in contrast to typically unilateral lesions following vascular injury (Greenwald et al., 2003). Direct contusions to the frontal and temporal lobes and diffuse axonal injury sustained as a result of TBI can affect executive functioning. Patients with a TBI may present with cognitive and behavioral deficits in the presence of minimal physical impairment because of these patterns of injury. Importantly, age when injured and injury severity were significantly associated with poorer outcomes in children with TBI (Keenan et al., 2018). Thus, ongoing clinical surveillance is important for children severely injured at a young age.

 

14.4.2.3.1 Counsellor Assisted Problem Solving Therapy

Key Points

Counsellor assisted problem solving programs may be effective in improving executive function in adolescents post TBI; especially older adolescents (14-17 years), adolescents who suffered a severe TBI, and those with poor speech.

Problem-solving therapies have shown promise for rehabilitating deficits post TBI in both adult and pediatric populations (Krasny-Pacini et al., 2014; Kurowski et al., 2014; Wade et al., 2014b). In particular, Counsellor Assisted Problem Solving Therapy (CAPS), a web-based problem-solving program, has gained status as an effective intervention used to improve cognitive and behavioural deficits in children post TBI. Multiple studies have compared CAPS to other internet-based interventions and have found evidence supporting its benefit in the executive functioning of pediatric patients post-TBI, particularly adolescents (Kurowski et al., 2013; Tlustos et al., 2016; Wade et al., 2014b; Wade et al., 2015b).

Linden et al. (2016) conducted a meta-analysis that confirmed that the CAPS intervention was beneficial in remediating executive functioning, however, only a small to medium effect size was found. A clinically important effect on the patients was deemed to be unlikely.

Discussion

Adolescents who underwent a counsellor assisted problem solving program (CAPS) were compared to a control group who were given standard internet resources. Older adolescents (≥14 yr) in the treatment group showed significant improvements in executive function, specifically behavioural regulation and metacognition compared to controls (Kurowski et al., 2013). Adolescents in grade 9-12 improved the most in executive function after the intervention according to primary caregiver’s rating at 12 months post-injury. Upon further analyses, Kurowski et al. (2014) found that older adolescents maintain their improvement in executive functioning up to 18 months post-intervention. Interestingly, younger adolescents did not significantly improve in caregivers’ ratings of executive function relative to the controls, even as they aged over the 18 month follow-up. Older adolescents may be more capable of using the training program than younger teens and as such the age of the patient at the time of the intervention may be important (Kurowski et al., 2013). Two other moderating variables were reported. Adolescents who sustained a severe, but not moderate, TBI had greater improvements in executive functioning post-intervention than the control group and. Adolescents with poor vocabulary improved in metacognitive abilities when in the CAPS group compared to the control group (Karver et al., 2014).

Conclusions

There is level 1a evidence that online counsellor-assisted problem solving programs may be superior to internet resource groups at improving executive function in adolescents post TBI.

There is level 1a evidence that older adolescents (14-17 years) benefit from counsellor-assisted problem solving programs more than younger (12-14 yr) adolescents in terms of improvements in executive functioning post TBI.

There is level 1b evidence that adolescents with a severe TBI, or poor vocabulary, benefit more from a counsellor-assisted problem solving program than adolescents with a moderate TBI, or adequate vocabulary, in terms of improvements in executive functioning post TBI.

14.4.2.3.2 Metacognitive Therapy

Key Points

The Strategic Memory Advanced Reasoning Training (SMART) intervention may improve high-order cognitive functioning in adolescents post ABI.

Goal management therapy may reduce parental ratings of their child’s executive dysfunction.

Therapist-assisted metacognitive treatment programs for pre-adolescents likely improve executive function and increase the use of metacognitive learning strategies post ABI.

Interventions that target problem solving may be effective at improving executive function and metacognitive abilities post ABI.

The following section reviews studies which investigated the efficacy of metacognitive therapy programs for improving executive function in pediatric patients post ABI. Some of the interventions/programs employed include the Strategic Memory Advanced Reasoning Training (SMART) program, Metacognitive Dimension Program, Attention Improvement Management program, and a multi-component cognitive-behavioural treatment programme.

Discussion

Other interventions have been developed to target the development of metacognitive strategies for children post-TBI. In one intervention, children were paired with psychology students and given the opportunity to use their metacognitive strategies and cooperative learning in daily activities and games (Braga et al., 2012). Post-treatment, children decreased the use of ineffective metacognitive behaviours and increased in beneficial ones such as planning, regulating, and monitoring behaviours (Braga et al., 2012). Treble-Barna et al. (2016) had similar goals, but used a computerized program to deliver metacognitive instruction and attention tasks. Parent ratings of executive functioning improved significantly, suggesting that children may improve in everyday executive functioning tasks, metacognitive skills, and regulation of behaviours after metacognitive training. Krasny-Pacini et al. (2014) used a goal management intervention with metacognitive strategies and coaching guides. By the end of the study, all children decreased in cognitive executive impairments for assigned tasks and parental ratings of executive function improved overall (Krasny-Pacini et al., 2014). However, when a new task was introduced 6 months post-intervention, the children fell back to pre-treatment levels of performance, suggesting a lack of generalizability.

Catroppa et al. (2009) developed a pilot intervention program with three participants, requiring children to attend instructional sessions on cognitive behavioural and psychosocial skill developments post TBI. Preliminary results indicate that cognitive inflexibility was significantly improved in 2 participants; however, all other measures were not significant or only one participant had a significant effect (Catroppa et al., 2009). Future studies with an increased sample size are needed before conclusions can be drawn. Furthermore, Cook et al. (2014) used a “SMART” program for adolescents post-TBI. The SMART program focused on top-down executive function training whereas the control memory group focused on bottom-up processing. The SMART program was more effective in remediating deficits of high order cognition when compared to the memory group. Specifically, adolescents in their chronic
phase of recovery were able to extract meaning from complex information. This improvement in topdown processing may in turn influence bottom-up processing, such as recall ability (Cook et al., 2014).

A few studies have targeted problem solving in order to improve executive functioning in children postABI. Chan and Fong (2011) examined a problem solving intervention that emphasized metacognition to improve executive function compared to usual care. Children with an ABI in the chronic recovery phase performed better in regards to abstract reasoning, metacomponential function, and perceived themselves as having better performance in everyday tasks. Importantly, the problem solving intervention was targeted to relate to everyday skills and situations, thereby increasing generalizability and potential usefulness of the increased behaviours (Chan & Fong, 2011). In another case series 5 children, all under the age of 12, participated in a computer based training program to decrease undesirable behaviours, and improve positive cognitive behavioural outcomes. Results indicated that participants improved in their overall ability to problem solve (Suzman et al., 1997). Similarly, Missuina et al. (2012) used an individualized treatment program (CO-OP) to teach children cognitive strategies and problem solving skills that are necessary for successful occupational performance. Children overall improved in functional performance, with increased ability to perform their own identified goals. This improvement was maintained at the 4 month follow-up. Authors suggest that perhaps adaptation to the CO-OP program may be necessary to further enhance effects.

Conclusions

There is level 1b evidence that the Strategic Memory Advanced Reasoning Training (SMART) program may improve higher-order cognitive deficits compared to bottom-up processing training in children post TBI.

There is level 1b evidence that metacognitive therapy may improve learning strategies and executive function compared to usual care in children and adolescents with an ABI.

There is level 4 evidence that the use of goal management therapy may improve parental ratings of executive function in young children who have sustained a TBI.

There is level 2 evidence that metacognitive problem-solving skills training may improve executive function and metacognitive abilities compared to no intervention in children post ABI.

 

14.4.2.4 Rehabilitation of Communication Deficits

Key Points

Speech therapy using electropalatography might improve articulation in children post TBI.

Peer-group training of pragmatic language skills might improve communication in children post ABI.

Communication has been described as the “heart of learning, living adequately in society and developing one’s unique personality” (DePompei & Hotz, 2001). An ABI often results in several long-term consequences, potentially including an inability to communicate adequately (Savage et al., 2005). During childhood, language and communication skills are continuously maturing and when brain injuries occur there may be an abnormal delay in the emergence of skills or a reduction in eventual mastery levels (Didus et al., 1999). For example, pragmatic language skills undergo development until at least the age of 12 years. When these skills are impaired and proper development does not occur, the child’s ability to effectively interact with peers is affected, in turn impacting social processes (Didus et al., 1999; Savage et al., 2005).

Several aspects of communication have been described, among them are the use of: listening, speaking, reading, writing and gesturing to understand an idea or to express thoughts. ‘Speech’ refers to the production of sounds that make up words and sentences, while, ‘language’ implies the use of words or ideas to express or interpret thoughts. Finally, ‘cognitive communication’ refers to the use of language and underlying processes (attention and problem solving, etc.) to communicate effectively. There are 3 types of language abilities (receptive, expressive and pragmatic) that can be affected by an ABI (Savage et al., 2005), either individually or as a group (DePompei & Hotz, 2001). Several interventions have been explored for individuals whose communication has become impaired as a result of an ABI. The most common approach is therapy targeting accommodations, however, other therapies include targeting remediation and metacognitive strategies (Turkstra et al., 2015). The methodological details and results from two studies investigating these interventions for the rehabilitation of communication deficits in children post ABI are listed in Table 14.23.

 

Discussion

Two different interventions examined the effects of speech and/or language therapy for children following an ABI. The first intervention evaluated the effectiveness of treating three teenagers with electropalatography (Morgan et al., 2007). Electropalatography “is an instrumental treatment technique allowing visual feedback of tongue to palate movement during real time articulation”. All participants had improvement in the perceptual measure for articulation and speech intelligibility. Electropalatography treatment may be an effective rehabilitative tool to improve speech post TBI (in particular, phenome, word or sentence art) (Morgan et al., 2007). The second intervention examined the effectiveness of a peer-group training program aimed at improving pragmatic skills in adolescents with a brain injury (Wiseman-Hakes et al., 1998). Following the intervention, adolescents improved both in pragmatic language behaviours (i.e., intelligibility of speech, syntax, topic, etc.) and in a range of pragmatic communication abilities (i.e., conversational skills, emphasis of meaning, use of context to convey message, etc.).

Conclusions

There is level 4 evidence that electropalatography treatment may be effective at improving the articulatory component of dysarthria post TBI in children.

There is level 4 evidence that peer-group training of pragmatic language skills can improve pragmatic language behaviours and range of pragmatic communication abilities in children post ABI.

14.4.2.5 Rehabilitation of Self-Awareness

Key Points

Injury-related information provided to participants and parents may not have an effect upon deficit self-awareness in children post TBI.

Children may have difficulties in understanding the extent of their brain injury (Krasny-Pacini et al., 2014; Wolfe et al., 2015). This can lead to a lack of awareness of any injury-related deficits, ultimately resulting in increased anxiety or poor self-esteem. Not only that, but lack of self-awareness regarding post ABI deficits may limit the ability of children to alter or compensate for inappropriate behaviour in social situations. Support for this theory has been garnered from studies that found imprecise self-ratings of skill are associated with lower social and academic proficiency (Gresham et al., 2000; Wolfe et al., 2015). Since parents are the major source of information for children, a child’s understanding of his or her injuries likely depends upon his or her parents’ level of understanding and knowledge about ABI. Thus, providing injury-related information to pediatric brain injury patients and their families should improve their awareness of injury-related deficits, which could indirectly improve cognitive processes and their social interactions.

Discussion

A single RCT evaluated the effect of injury-related information interventions for patients’ self-awareness regarding their injury (Beardmore, 1999). Although the intervention was not effective in improving the children’s knowledge or awareness of their deficits, self-esteem, or cognitive measures, it did significantly reduce the stress experienced by their parents. Additional studies using larger sample sizes should be conducted to elucidate the effects of injury-related information interventions upon children and their families.

Conclusions

There is level 1b evidence that injury-related information interventions may not improve knowledge or awareness of injury-related deficits compared to placebo information sessions in children post TBI.

14.4.3 Motor Rehabilitation

Motor capacity is another aspect of functioning that is often impaired following an ABI. Improvements in motor function have been reported in children after sustaining an ABI, however, differences in gait velocity, stride length, and hand function may persist in the long term (Kuhtz-Buschbeck et al., 2003). Therefore, despite improvements in overall function, residual impairments are common. Baque et al. (2016) report from a systematic review on motor rehabilitation that both physiotherapy and virtual reality result in favourable outcomes in the pediatric population. Other therapies that have had success within the adult ABI population for rehabilitation of motor abilities are bracing, botulin toxin, and constraint induced movement therapy (CIMT). However, there is lack of high-quality research investigating motor rehabilitation therapies post ABI in the pediatric population.

14.4.3.1 Bracing

Key Points

It is unclear whether upper limb lycra splints improve the quality of movement in children post TBI.

In the growing child, bracing is often utilized to prevent contracture formation by providing regular stretching, or to improve functional gait and upper extremity use. Evidence from animal studies is often quoted in support of bracing children with spasticity, as there is data showing that stretching of muscles can negate the atrophic effects associated with spasticity, and thus promote muscle growth (Ziv et al., 1984).  Unfortunately, data analyzing the impact of bracing children with a TBI is limited and the methodological details/results from one study are presented in Table 14.25.

Discussion

Corn et al. (2003) have studied the impact of utilizing second skin lycra splinting on the quality of upper limb movement in children. Due to low numbers (only 2 of 4 subjects being diagnosed with traumatic brain injury) and a single subject design, this data may not be generalizable to the broader TBI population. Lack of improvement in one child and significant improvement in another, as documented with the Melbourne Assessment of Upper Limb Function, highlights the need for goal focused use and careful measurement of outcomes when requesting a child and their family undertake a bracing protocol, which may be time consuming and uncomfortable.

Conclusions

There is inconclusive (level 4) evidence regarding whether or not upper limb lycra splints improve the quality of movement in children post TBI.

14.4.3.2 Constraint-Induced Movement Therapy

Key Points

Constraint induced movement therapy may improve upper limb function in children post TBI, however, further research is required.

Constraint induced movement therapy (CIMT) has received increased attention in the literature as a possible treatment for cerebral palsy in children and stroke in adults. This treatment has two key components; first, the limb that is least or not at all impaired is constrained. Following this, a therapist leads the patient in a program of intensive, repetitive daily motor movements that are performed with the affected limb (Cimolin et al., 2012). The mechanism underpinning this approach involves using the impaired limb to promote neuroplasticity and cortical reorganization (Gordon & Di Maggio, 2012). This type of treatment has been shown to be effective in adults who have suffered a stroke, a TBI, or focal hand dystonia, however, little research has been conducted in children with ABI. The methodological details and results from one study investigating constraint-induced movement therapy for motor rehabilitation in children post ABI are listed in Table 14.26.

Discussion

In a recent case control study looking at the effectiveness of CIMT with children post TBI, Cimolin et al. (2012) found that motor function improved post intervention in the hemiparetic limb of each child who had sustained a TBI. Prior to treatment, movements with the affected arm were slower and took longer. Post intervention, improvement was noted in the arm’s overall range of motion and the execution of movement. Gross motor function also improved significantly following CIMT therapy compared to baseline, however, the authors suggest that such improvement may be attributed to spontaneous recovery over time. Considerable debate exists regarding this last finding, as it is unclear whether motor improvements after CIMT are in fact due to the CIMT or the multiple hours of therapy the patient undergoes per week. Furthermore, despite findings from Cimolin et al. (2012), there are concerns for CIMT in the pediatric population, such as tolerability of such intense treatment, inability to deal with psychological effects from frustration, and difficulties with bimanual movements (Cimolin et al., 2012). Therefore, future studies where controls, who are also patients with TBI, undergo the same amount of therapy without splinting of the less affected limb are required to determine whether the benefits of CIMT outweigh the risk when treating pediatric patients post TBI.

Conclusions

There is level 2 evidence that constraint-induced movement therapy (CIMT) may improve motor function of the hemiparetic limb compared to no care in children post TBI.

14.4.3.3 Technological Aids in Motor Rehabilitation

14.4.3.3.1 Virtual Reality and Videogame Therapy

Key Points

Virtual reality-based therapy focused on walking and balancing exercises may improve certain movements (pelvic and ankle kinematics) but not others (knee flexion) in pediatric patients post ABI.

Movement therapy using a Nintendo Wii console might improve motor coordination, as well as engagement and intensity of physical activity in pediatric patients post ABI.

Alternative methods for motor therapy have focused on the use of modern-day technology to remediate motor deficits post ABI. The use of the Nintendo Wii videogame console has been found to be a cost-effective and highly-motivating alternative to traditional physical and cognitive treatment, as both limb movement and social interactions are promoted at the same time (Loureiro et al., 2010). The use of the Nintendo Wii and Wii-Fit software has also been found to be successful amongst adult populations for remediation of balance (Gil-Gómez et al., 2011) and moderately successful for improving walking (McClanachan et al., 2013). Other systems have been used, including virtual reality simulators (Bart et al., 2011), to recreate a real-world environment. Specifically, Bart et al. (2011) used a virtual reality simulator that could distinguish between children with and without ABI. The results revealed that virtual reality game scores were correlated with self-care abilities and upper-extremity reaching. As a result, it is concluded that virtual reality and videogame therapy can both identify and improve motor deficits present in children post TBI.

Discussion

The literature demonstrates that use of a gaming console such as the Nintendo Wii has made positive contributions to motor therapy in pediatric ABI. De Kloet et al. (2012) reported that patients demonstrated significant increases in amount and intensity of physical activity, coordination of movement, and participation in a greater variety of recreational activities following 6 weeks of Nintendo Wii therapy. However it was conceded that quality of life was not measured so while motor functions improved, psychosocial issues may not have been addressed (De Kloet et al., 2012). Future pediatric research is required to assess the effectiveness of similar interfaces such as the Xbox Kinect system which operates without a controller and measures the player’s own body movements.

Biffi et al. (2015) reported that paediatric patients with an ABI demonstrated significant improvements in multiple aspects of gait and walking ability, particularly in pelvic kinematics after performing walking and balance exercises in a virtual reality environment. However, certain parameters such as knee flexion did not improve. It is important to note that while left and right-side mean pelvic tilt, pelvic tilt at initial contact, right-side hip extension, left-side ankle plantar-flexion and ankle dorsi-flexion all significantly differed compared to the healthy control group at baseline, there were no longer any significant differences post-treatment. However, one major limitation was the lack of an age and condition-matched control group (Biffi et al., 2015). The current literature suggests that simulators are a user-friendly, safe and motivating tool that can be used as part of a therapeutic intervention, however, further studies are required to support their use as main-stays in motor therapy post ABI.

Conclusions

There is level 2 evidence that walking and balance exercises performed in a virtual reality environment can improve pelvic and ankle kinematics, but not knee flexion, compared to healthy controls in children post ABI.

There is level 4 evidence that use of a Nintendo Wii console can improve motor coordination, as well as the amount and intensity of physical activity that a patient participates in, in children post ABI.

14.4.3.3.2 Robot Mediated Therapy

Key Points

Body-weight supported treadmill training with an exoskeleton combined with physiotherapy may be superior to physiotherapy alone at improving gait and motor function in pediatric patients post ABI.

A wearable ankle robot combined with a computer game interface might reduce spasticity and improve balance in pediatric patients post ABI.

Robot Mediated Therapy (RMT) combined with goal-oriented reaching tasks might improve upper limb motor function and spasticity in pediatric patients post ABI.

Currently, there is a lack of studies addressing robot-assisted training among pediatric patients with an ABI (Fasoli et al., 2012). In a study of patients with an ABI (predominantly cerebral palsy and stroke), Keller et al. (2016) reported that use of the ChARMin exoskeleton for upper limb rehabilitation was feasible for all patients thereby highlighting the promise of this type of intervention. Robot-assisted therapy facilitated motor recovery within the cerebral palsy and stroke populations and may be beneficial for children who have sustained an ABI. Four studies have evaluated the use of robotic assistance for motor rehabilitation in the pediatric population.

Discussion

Four robotic assisted therapies were examined, three for remediation of lower limb motor function (Biffi et al., 2015) with one focusing specifically on ankle remediation (Chen et al., 2018), and one for the upper limb (Frascarelli et al., 2009).

Beretta et al. (2015) used a body-weight supported treadmill in combination with physiotherapy to re-train gait performance in children following an ABI. There was a global improvement in both motor and functional abilities of the lower limbs in children who received robotic assistance and physiotherapy compared to those who received standard physiotherapy alone. Specifically and perhaps more importantly, standing and walking abilities improved post-treatment (Beretta et al., 2015; Biffi et al., 2015), which is in line with findings from the adult TBI population (Wilson et al., 2006). Beretta and colleagues (2018) performed a follow-up study with additional participants. The authors found significant between-groups difference on gross motor function for standing and walking, showing improvement in the robotic assistance group. Both groups showed significant improvement on other measures, however, they were not significantly different from each other. Lastly, a study investigating a wearable robot for ankle remediation used a computer game interface and measured biomechanical forces of the ankle (Chen et al., 2018). In this pre-post study, the authors found a significant improvement in reduction of spasticity and increases in balance scores (Chen et al., 2018). This study does not include a control group and has a low sample size of 10 pediatric individuals. Further investigation is needed to make conclusions about it’s use in rehabilitation.

Furthermore, Frascelli et al. (2009) report that upper limb motor function and spasticity are improved following short term robot mediated therapy on reaching tasks. Authors suggest that recovery in upper limb motor function can be influenced by repetitive training with a robotic arm, without negatively affecting muscle tone (Frascarelli et al., 2009).

Conclusions

There is level 2 evidence that exoskeleton, body-weight supported treadmill training paired with physiotherapy may be superior to physiotherapy alone at improving gait and motor function in pediatric patients post ABI.

There is level 4 evidence that an wearable ankle robot combined with a computer game interface may be beneficial in reducing spasticity and increasing balance in children post ABI.

There is level 4 evidence that Robot Mediated Therapy (RMT) combined with goal-oriented reaching tasks may improve upper limb motor function and spasticity in children post ABI.

14.4.3.4 Pharmacological Treatment of Spasticity

Key Points

Botulinum toxin type A, when used in combination with adjunct therapy (physiotherapy andoccupational therapy), may effectively reduce upper and lower limb spasticity to improve movement range of motion, in children and adolescents following ABI.

Intrathecal baclofen pumps may reduce upper and lower limb spasticity in children with hypoxic brain injuries, however, intrathecal pump implantation may be associated with complications such as infections and skin protrusions. Side effects may be mitigated by subfascial pump implantation.

Spasticity and elevated muscle tone are common complications that arise after an individual has experienced an ABI (Popernack et al., 2015). Spasticity has been broadly defined as “disordered sensorimotor control, resulting from an upper motor neuron lesion, presenting as intermittent or sustained involuntary activation of muscles” (Pattuwage et al., 2017). When damage occurs to the upper motor neurons of the corticoreticular pathway in the brain, an increase in muscle tone and exaggerated deep tendon reflexes may occur (Pattuwage et al., 2017). Muscle tone is defined as “velocity-dependent resistance of a muscle to stretching” (Pattuwage et al., 2017).

Within the pediatric population, spasticity has a range of implications from producing mild discomfort to extremely painful spasms, muscle contractures, pressure sores, and interfering with activities of daily living (Pérez-Arredondo et al., 2016). In order to prevent or delay long-term damages due to spasticity, several pharmacological and non-pharmacological approaches exist (Walter et al., 2015). Generally, clinicians begin with non-invasive/non-pharmacological approaches first, including physiotherapy, splinting and casting. If these treatments fail to work, they may gradually move to more invasive/pharmacological approaches using dantrolene, tizadine, botulinum toxin and baclofen (O’Brien, 2002; Pattuwage et al., 2017). These pharmacological agents reduce spasticity through a variety of different mechanisms:

  1. Dantrolene reduces spasticity through inhibition of calcium release from the sarcoplasmic reticulum at the myoneural junction.
  2. Tizadine inhibits the alpha-2 adrenergic system at the spinal and supra-spinal levels to reduce spasticity.
  3. Local injections of botulinum toxin reduce spasticity through inhibition of intracellular acetylcholine secretion.
  4. Balcofen inhibits the neurotransmitter gamma aminobutyric acid to prevent spinal reflexes from neurons that use it at the spinal interneuron level, in turn reducing spasticity.

A review of the literature on botulinum toxin suggests that injections are effective for lower limb functional improvements, however, future research is needed to determine the effects for the upper limb (Gordon & Di Maggio, 2012). This section reviews the administration and effectiveness of intrathecal baclofen and botulinum toxin in children post ABI.

Discussion

Two studies evaluated the effectiveness of botulinum toxin type A (BTX-A) for the management of spasticity in children with an ABI. Overall, BTX-A improved spasticity and range of motion in children and adolescents with an ABI (Guettard et al., 2009; van Rhijn et al., 2005). When BTX-A for both upper and lower extremities was paired with other therapies (physical, occupational and exercise therapy) improvements were seen not only in spasticity and range of motion, but also voluntary motor control. However, due to the lack of comparison groups, conclusive statements about the efficacy of BTX-A are difficult to make. Currently, it is unclear if the improvements in spasticity and mobility were due to the combination of therapy, BTX-A alone, or the standard therapy. Future research should differentiate these groups to compare effectiveness (Guettard et al., 2009). Importantly, BTX-A treatment was not associated with any adverse side effects for injection doses under 10 U/kg of botulinum toxin (Guettard et al., 2009; van Rhijn et al., 2005). As such, Intra-muscular BTX-A injections may be considered a safe treatment for severely brain-injured children, and effective when used in combination with orthotic devices and specific functional exercise programs.

An intrathecal baclofen injection pump improved spasticity in three young children (Walter et al., 2015). However, unlike botulinum toxin, side effects were reported with the use of the intrathecal baclofen pump implant treatment. Two of the three patients had complications, with five of the complications being related to the device. Two of these complications were due to skin protrusions, as the pumps must be implanted under the skin and one child experienced problems with epifascial implantation. However these effects were minimized with modification of the protocol to a subfascial implantation, which has become the sole technique for intrathecal baclofen pump implantations for children (Walter et al., 2015). Other complications were due to wound infection, cerebrospinal fluid leakage, and intractable spasticity. All complications were reversed with treatment or relocation of the pump.

Conclusions

There is level 2 evidence that botulinum toxin type A (BTX-A) used in combination with adjunct therapy (physiotherapy, occupational therapy) may decrease upper and lower limb spasticity, as well as movement range of motion, in children and adolescents post ABI.

There is level 4 evidence that intrathecal baclofen pumps may be effective at reducing spasticity in the upper and lower limbs for children with ABI as a result of hypoxia.

14.5 Vestibular Recovery

Key Points

Home based exercise programs likely improve functional balance, aerobic capacity, and dexterity in children with an ABI, however, after 6 weeks, they have similar effects.

Vestibular dysfunction is commonly overlooked in both the adult and pediatric population post ABI. Symptoms may include vertigo, balance problems, visual complaints (double vision, blurriness), and nausea. Mann and Black (1996) noted that the most common persisting vestibular symptom after TBI is positional vertigo (symptoms provoked by head movement). Head trauma has been shown to be the third most common cause of childhood vertigo, accounting for 14% of all cases (Gioacchini et al., 2014), and therefore should not be overlooked. Unfortunately, the majority of research on vestibular dysfunction following brain injury is for sports-related mild TBIs. Two studies were conducted looking at treatment for balance deficits in children following a severe ABI (Katz-Leurer et al., 2008; Katz-Leurer et al., 2009). The results and methodological details from these studies are presented in Table 14.30.

Discussion

Home based exercise programs are effective at improving motor function in children who have sustained an ABI (Katz-Leurer et al., 2008; Katz-Leurer et al., 2009). Both of the home based exercise programs studied were considered short term intensive programs and were implemented in the chronic phase of brain injury rehabilitation. In the 2008 study, balance and motor coordination (Sit-stand-sit, step-up exercises) and walking performance (2 Minute Walk Test, Walking Speed) improved within the group of children that received exercise therapy. However, there was no generalized effect for unpracticed motor skills (i.e. grasping action) (Katz-Leurer et al., 2008). In theory it would be beneficial for training programs to create positive transfer of practice tasks to everyday activities (Katz-Leurer et al., 2008), but this was not studied. Within this study population, there was variation in the number of training days each child received and spectrum of etiology of ABI (Katz-Leurer et al., 2008)

When compared to a group of children who continued with daily activities, children in exercise therapy still improved in their functional balance performance (Time up and Go Test), aerobic capacity (repetitions in the sit-to-stand, and step-up sideways on preferred and non-preferred leg movements)  but not in walking performance (2 Minute Walk Test, Walking speed) (Katz-Leurer et al., 2009). These improvements were maintained immediately after the conclusion of the program, but not at the six week follow-up within the exercise group (Katz-Leurer et al., 2009). Results should be interpreted with caution as there appeared to be a high dropout rate for both studies (Katz-Leurer et al., 2008; Katz-Leurer et al., 2009). There also was a variation in children studied, as half of the participants had cerebral palsy and a subgroup analysis was not conducted to determine the effects of the exercise specifically on children with TBI (Katz-Leurer et al., 2009). Overall, home based exercise programs seem to improve coordination, dexterity and aerobic capacity more significantly than simple regular daily activities in the short-term, however these benefits may not be maintained for longer than 6 wk.

Conclusions

There is level 1b evidence that home based exercise programs may be superior to regular daily activities at improving balance, dexterity, and aerobic capacity short-term (<6 weeks) in children post ABI.

14.6 Shaken Baby Syndrome

The constellation of injuries associated with non-accidental trauma sustained during infancy, such as retinal hemorrhage, intracranial and musculoskeletal injuries are generally known as shaken baby syndrome (SBS) (Joyce & Huecker, 2019). Shaken baby syndrome has also been referred to as whiplash-shaken infant syndrome, shaken impact syndrome, infant shaken impact syndrome, non-accidental or abusive head injury (Dias et al., 2005). Regardless of what it is called the impact on a young infant can be quite severe and even fatal.

Shaken baby syndrome occurs when a child is taken by the torso, leg, or arm and vigorously shaken in an angular movement repeatedly (Joyce & Huecker, 2019). This acceleration and deceleration motion causes the brain to rotate within the baby’s skull, resulting in high gravitational forces transmitted to the brain (Deputy, 2003; Macdonald & Helfrich, 2001; Tsao et al., 2002). There are several unique factors in infants that render their brains highly vulnerable to damage with shaking, including the relatively high weight of an infant’s head, weak neck muscles, the thickness of the skull wall, the lack of myelination and the high water content of the infant brain (Lancon et al., 1998; Lewin, 2008; Showers, 1992). The force at which an infant is shaken causes blood vessels to rupture, resulting in bleeding within the brain and precipitation of further damage (Carbaugh, 2004; Macdonald & Helfrich, 2001). SBS is typically seen within the first year of life; however, cases have been reported up to the age of three (Duhaime et al., 1998; Lancon et al., 1998; Tsao et al., 2002).

14.6.1 Risk Factors & Incidence

Frustration with an infant’s frequent and inconsolable crying is believed to the most common risk factor for SBS. An infant will typically cry 1.5 to 3 hours a day but an excessive amount of inconsolable crying can occur— a period known as “colic” or “purple crying”. The frustration and anger felt by the caregivers during these periods of “colic” are often cited as the main trigger for shaking an infant (Carbaugh, 2004; Goulet et al., 2009; Lewin, 2008). Occurrences of SBS tends to increase between 2.5 to 4 months when the period of “colic” is at its highest (Goulet et al., 2009). Due to the undeveloped anatomy of an infant, they are at an elevated risk of developing long-term disabilities, impairments, injury and even death as a result of brain injuries (Gutierrez et al., 2004). Deaths from SBS account for 13-50% all non-accidental pediatric deaths recorded (Dias et al., 2005; Goulet et al., 2009; Lancon et al., 1998), and for the infants that survive severe neurological impairments and physical disabilities are recorded in over half of cases (50-75%) (Dias et al., 2005; Goulet et al., 2009). Additional risk factors for SBS include: male gender, difficult infant temperaments, prematurity, low-birth weight, special needs and medical fragility (Carbaugh, 2004; Lewin, 2008).

14.6.2 Diagnosis/Clinical Findings

As the clinical symptoms of SBS are non-specific, each case tends to vary in its presentation. Minor symptoms of SBS can be mistaken for other childhood illnesses which lead to challenges in recognizing the syndrome. Common clinical signs include irritability, seizures, impaired consciousness, bulging fontanelle or forehead, inability to focus the eyes, breathing abnormalities, vomiting, lethargy, constipation, poor feeding, apnea and muscle weakness (Altimier, 2008; Carbaugh, 2004; Duhaime et al., 1998; Lewin, 2008). Any Infant who has been the victim of SBS should undergo a complete assessment and receive immediate care and attention (Gutierrez et al., 2004).

Assessments such as neurologic and ophthalmologic examinations, skeletal survey, CT and MRI of the head are used to diagnose SBS (see Table 14.27) (Coody et al., 1994; Duhaime et al., 1998). CT scans have been shown to be superior to MRI when viewing the damage to the infant’s brain, especially since findings like  intracranial hemorrhage, hairline skull fractures, and compression fractures in the skull are all visible on CT scan (Coody et al., 1994). In infants where CT findings are not definitive, MRI has been shown to be useful in detecting extra axial hemorrhages (Duhaime et al., 1998). t

A common finding in SBS, which has been reported in 65 to 95% of those affected, is retinal hemorrhage (RH) (Duhaime et al., 1998). The amount of force it takes to cause RH is unknown. Duhaime et al., (1998) noted that although RH is not specific to SBS, the appearance of “severe bilateral retinal hemorrhage with retinal folds or detachments” is.

14.6.3 Treatment

Evidence regarding the types of treatment used specifically in the SBS population is scarce and requires more research.  However, the type of treatment typically used parallels the treatment regimen of a TBI and is mostly supportive (Joyce & Huecker, 2019). The goal of treatment is to maintain normal blood and intracranial pressure to ensure adequate cerebral perfusion occurs (Joyce & Huecker, 2019).

The initial management of SBS is to maintain the patient’s airway, breathing and circulation. If a child presents with no alterations of consciousness and normal blood pressure, they may be treated with supportive care (Joyce & Huecker, 2019). However, if a child presents with a Glasgow coma score of less than 9, respiratory distress or hemodynamic instability they may require intubation and mechanical ventilation to enhance oxygenation and prevent aspiration (Joyce & Huecker, 2019). An important consideration when performing advanced airway management is to maintain cervical spine stability (Joyce & Huecker, 2019). For the initial monitoring of ventilation, capnography is recommended to avoid hyperventilation and subsequent hypocapnia, which leads to vasoconstriction and decreased cerebral perfusion (Joyce & Huecker, 2019).

The treatment of immediate brain injury from the initial traumatic forces is equally important to the prevention of secondary brain injury that may occur (Joyce & Huecker, 2019).  This includes preventing coagulation, hypoxemia, intracranial hypertension, hypercarbia, hyperglycemia or hypoglycemia, electrolyte abnormalities, hematomas, seizures and hyperthermia (Joyce & Huecker, 2019). Managing intracranial pressure is crucial in preventing secondary brain injury (Joyce & Huecker, 2019).  Intracranial pressure may be decreased by raising the patients head to 30 degrees (Joyce & Huecker, 2019).  This optimizes CPP and improves venous drainage without affecting cerebral blood flow (Joyce & Huecker, 2019).

If intracranial hypertension is present, the patient will require sedation with barbiturates (Joyce & Huecker, 2019). Barbiturates work to lower intracranial pressure by decreasing cerebral metabolism and blood flow (Joyce & Huecker, 2019).  In addition, therapeutic hypothermia may reduce cerebral metabolic demands and prevent secondary brain injury (Joyce & Huecker, 2019).

If a patient is not responding to supportive therapy or is demonstrating signs of herniation or neurologic deterioration a decompressive craniectomy may be necessary (Joyce & Huecker, 2019).  This surgical procedure removes a portion of the skull to allow for swelling and limits secondary injury (see section 14.2.3.1). However, aggressive treatment of an infant with poor prognosis outcomes has been questioned since most cases result in death despite continuous management (Duhaime et al., 1998).

14.6.4 Long-Term Outcomes

SBS can result in many possible long-term consequences such as “permanent brain damage, visual impairments, developmental delays, disabilities and motor impairments, paralysis, eye damage, hearing loss, blindness, decreased movement from spastic muscles, seizures and even death” (Carbaugh, 2004). Death occurs in approximately 5-35 percent of affected infants (Joyce & Huecker, 2019).

Eighty-four SBS cases were contacted to determine long term outcomes in a study conducted by Duhaime et al. (1998). Only 14 individuals completed the study and the mean duration of time elapsed since injury was 10 years. One patient died 5 years post injury but up until that time was in a vegetative state. Six patients were severely disabled, two patients were moderately disabled, and 5 patients presented with good outcomes. Associations were found between the severity of abnormalities in the acute stage of SBS and their long-term outcomes. Five patients who were unresponsive at acute care remained in a vegetative state or severely disabled long term. At acute care, six patients required intubation and all of these cases were described as having severe or moderate disabilities. Children who presented with bilateral or unilateral subdural hematoma on CT were found to have a severe disability at time of follow-up. Overall, children who were intubated, unresponsive, or who had a unilateral or bilateral subdural hematoma on CT while in acute care, had worse long term outcomes.

The cases of 404 children with SBS were reviewed by Bourgeois et al. (2008), to examine the prevalence of associated seizure disorder and how this related to SBS outcomes. Seventy-three percent of children (296 children) presented with seizures, with 50% of these patients displaying multiple seizure types. Behavioral problems were found to be closely associated with seizures, occurring in 96% of patients with chronic epilepsy. Seizure activity was found to be associated with worse outcomes for children with SBS.

In a case control study by Stipanicic et al. (2008), 11 SBS patients were compared to 11 healthy controls. It was found that SBS patients has significantly worse IQ scores (Stanford-Binet Intelligence Scale), comprehension of instructions and verbal fluency (NEPSY), time to complete an assignment (TMT-B, HRB-PF), and memory (digit-span backwards) compared to healthy controls.

King et al. (2003), reviewed the charts of 364 patients to determine the typical clinical characteristics of SBS, and related outcomes. Clinical features of SBS included seizures (45%), decreased consciousness (43%) and respiratory difficulties (34%). Retinal haemorrhages, which were found to be associated with neurological deficits, subdural haemorrhages and death, were present in 76% of patients. Many patients (85%) were found to need ongoing multidisciplinary care for moderate to severe disability or were in a vegetative state.

14.6.5 Ophthalmological Outcomes

Retinal hemorrhages (RH) have been found in 65-95% of infants with SBS (Duhaime et al., 1998). Two theories exist regarding the etiology of RH in SBS. One suggests that the RH occurs due to retinal venous obstruction secondary to increased ICP, while the second postulates that when an infant’s head is accelerating/decelerating, traction develops between the vitreous and the retina leading to RH (Kivlin et al., 2000). RH is a clinical presentation that should lead to clinician to pursue a CT scan of the head (Kivlin et al., 2000).

Kivlin et al. (2000) noted that RH was found in 79% of the entire study population (n=123). Of those, bilateral RH was found more frequently (68%) than unilateral RH (11%). Of the 36 patients who died, ophthalmologic examination revealed a lack of visual response in 35, poor pupillary response in 26, and RH in 34 patients. Study authors suggest the presence of these symptoms positively predicted fatal outcomes and severe neurological disability for those children with SBS (Kivlin et al., 2000). Furthermore, the researchers also noted that while patients who experienced seizures were less likely to die than those who didn’t, seizures were associated with poor vision at follow-up.

Of the 30 cases reviewed by McCabe & Donahue (2000), subdural hemorrhages were detected in 21 patients and were more common than intracerebral (n=11) and subarachnoid (n=10) hemorrhages. Seizure activity occurred in 67% of the study population. All 8 patients who died had nonreactive pupils 6 of the patients who died had a midline shift detected on CT. It was determined that lack of visual response and a midline shift are predictors of fatal outcomes in SBS.

In a case series of 10 patients, Mills (1998) studied how ophthalmologic examinations of SBS individuals predicted future outcomes. Of note, intraretinal hemorrhages were found in all patients but were not found to be significantly associated with fatal outcomes. Further, a lack of visual response was found in 4 patients, 3 of which later died, and circular perimacular retinal folds and peripheral retinoschisis were also found in all 3 individuals who died. Moreover, in a case series of 14 children in Wilkinson et al. (2014), the severity of RH predicted the severity of acute neurological outcomes. Other predictors of severe neurological injury included vitreous or subhyaloid hemorrhages.

14.6.6 Education & Prevention

Key Points

The PURPLE intervention for shaken baby syndrome may increase knowledge about crying and the effects of shaken baby syndrome among caregivers. It may also increase protective behaviours among caregivers, such as walking away during a period of inconsolable crying in their infant.

Education programs on infant crying and safety may be effective at informing parents about the dangers of shaken baby syndrome, helping change their behaviour, and reducing the number of shaken baby syndrome.

The “Don’t Shake the Baby” project implemented by Showers (1992) provided a basis for future SBS educational programs to build upon. “Don’t Shake the Baby” included an information card providing tips on how to calm a crying infant and a response card to be filled out by new parents. Evaluation of the program led to the conclusion that there needed to be more education provided to parents on the dangers of shaking infants and on how to properly care for a crying infant (Showers, 1992).

The prevention of SBS appears to be related to the education received by parents either prior to delivery at routine office visits, during prenatal visits, prenatal classes and/or post-delivery prior to discharge home (Walls, 2006).

Discussion

A commonly used intervention for educating mothers about SBS and the strategies used to prevent such injuries is called PURPLE. Each letter in PURPLE represents a characteristic of crying in infants that is troublesome for caregivers, potentially leading to SBS (Fujiwara et al., 2012). The PURPLE intervention has been shown to improve maternal knowledge of infant crying compared to an infant safety information control group (Barr et al., 2009; Fujiwara et al., 2012). Improvement in knowledge about infant shaking was not consistently identified, with two studies reporting no statistically significant improvement compared to the control group (Barr et al., 2009; Fujiwara et al., 2012) and one study reporting significant improvement (Barr et al., 2009). Overall, 95% of mothers post-intervention were reported to have a perfect score on knowledge of infant shaking following the PURPLE intervention, whereas only 57.4% scored perfectly on the crying knowledge subscale (Reese et al., 2014).

The improvement in knowledge of crying and shaking behaviours moderately translated into a change in behaviours following the PURPLE intervention. Mothers reported walking away from infant with inconsolable crying more than the control group (Barr et al., 2009; Fujiwara et al., 2012), and more mothers shared this information with other caregivers (Barr et al., 2009; Fujiwara et al., 2012). Two studies reported significant differences in caregivers who received PURPLE compared to controls in the sharing of information on the dangers of SBS with other caregivers (Barr et al., 2009) whereas another study reported no significant difference (Fujiwara et al., 2012). Overall, only 41% of mothers shared information that they had learned in the intervention with other care providers for their children (Reese et al., 2014). The most common reason for lack of sharing information was due to low perceived risk of infant shaking by the other caregiver. However, the majority of perpetrators of SBS are not mothers (Reese et al., 2014), and therefore the PURPLE intervention should be modified to increase the sharing of learned knowledge and to involve other caregivers.

Other educational programs have been evaluated for informing caregivers of the effects of SBS and its prevention. All of the programs that were implemented were short-term with little participant involvement. One program administered a brochure detailing on the steps to take when a child is crying inconsolably (Bechtel et al., 2011). Most programs used a brochure and short video (8-11min) combination (Altman et al., 2011; Deyo et al., 2008; Dias et al., 2005) and one used a talk from a pediatrician (Simonnet et al., 2014). These programs require minimal time to complete and are therefore attractive and relatively easily implemented. Programs that are administered within the hospital and provided through a healthcare professional are effective in communicating the dangers of shaking an infant (Altman et al., 2011; Bechtel et al., 2011; Deyo et al., 2008; Dias et al., 2005; Simonnet et al., 2014), helping parents change their behaviour, such as “taking a break if frustrated with a crying infant” (Bechtel et al., 2011), and were found to reduce the number of SBS cases post-implementation of the program (Altman et al., 2011; Dias et al., 2005).

Although all aforementioned studies improve caregiver knowledge on SBS, only a few evaluated the change in incidence of SBS following the educational interventions. Future research is warranted to determine the outcomes of educational interventions on rate of SBS.

Conclusions

There is level 1a evidence that the PURPLE intervention program may be effective for improving maternal knowledge of infant crying compared to an infant safety control group.

There is conflicting (level 1b) evidence regarding whether or not the PURPLE intervention program is effective at improving maternal knowledge of infant shaking, compared to an infant safety control group.

There is level 1a evidence that the PURPLE intervention program may be effective at improving maternal behaviours, such as walking away from an infant during inconsolable crying and sharing information on the dangers of shaken baby syndrome, compared to injury prevention educational materials.

There is level 4 evidence supporting the role of education programs for informing caregivers of children with shaken baby syndrome about its detrimental effects, helping parents change their behaviour, and reducing the number of shaken baby syndrome cases post intervention.

14.7 Conclusion

Overall the pediatric literature for ABI is sparse. It is imperative to determine preventative measures and interventions to reduce potential long-term effects of an ABI. Many of the interventions that were evaluated in this review have been studied and are effective in the adult ABI population. Children have different developmental trajectories compared to adults and there is also a developmental difference when comparing a young child to an adolescent. In children, a brain injury may affect the onset of a skill (i.e., skill acquisition may be delayed), the order of emergence of skills, the rate of skill development, and/or the degree to which complete development of a skill is attained. Therefore, health care professionals cannot generalize interventional studies conducted within the adult population to the pediatric ABI population. Further research is warranted in order to be able to make recommendations for the pediatric ABI population.

Summary


There is level 4 evidence that head elevation may reduce intracranial pressure, but not cerebral perfusion pressure, in children post TBI.

There is level 1a evidence that therapeutic hypothermia delivered for 24 hours is no different than normothermia at increasing mortality and unfavourable outcomes in children post TBI.

There is level 1a evidence that therapeutic hypothermia delivered for 24 hours may decrease intracranial pressure during cooling compared to normothermia in children post TBI.

There is level 1a evidence that therapeutic hypothermia delivered for 24 hours may decrease heart rate (24 hr post treatment), cerebral perfusion pressure (25-72 hr post treatment), and blood pressure (25-72 hr post treatment) compared to normothermia in children post TBI.

There is level 1a evidence that decreases in cerebral perfusion pressure and blood pressure during treatment with therapeutic hypothermia (for 24 hr) are associated with development of unfavourable outcomes in children post TBI.

There is level 1a evidence that therapeutic hypothermia delivered for 48 hours is no different than normothermia with respect to mortality or complications (arrythmias, coagulopathies, infections) in children post TBI.

There is level 1a evidence that therapeutic hypothermia delivered for 48 hours may temporarily (<24 h) lower intracranial pressure in children post TBI compared to normothermia.

There is level 1b evidence that hypothermia treatment maintained for 48 hours may preserve antioxidant defenses in children following a severe TBI, when compared to normothermia.

There is level 1b evidence that therapeutic hypothermia delivered for 72 hours with a cooling cap may improve short-term intracranial pressure (<72 hr) and reduce biomarkers of brain damage (S-100, NSE, CK-BB), compared to normothermia therapy in children post TBI.

There is level 4 evidence that hypothermia induced through cooling blankets placed on the patient’s bed may decrease the duration of hyperthermic state and acetaminophen administration upon arrival to the pediatric ABI inpatient unit.

There is level 1b evidence that spine injury severity and midline shift on CT scans, fixed pupils, abdominal injury, and subarachnoid hemorrhage are associated with mortality and unfavourable outcomes, respectively, at 3 months post-TBI in a pediatric population that underwent hypothermia treatment.

There is level 1b evidence that serum sodium concentrations are inversely proportional to intracranial pressure, and directly proportional to cerebral perfusion pressure, after hypertonic saline or Lactated Ringer’s solution therapy in children post TBI.

There is level 1b evidence that hypertonic saline is associated with a lower frequency of acute respiratory distress syndrome, shorter intensive-care unit stay, and lower rate of complications compared to treatment with Lactated Ringer’s solution in children post TBI.

There is level 4 evidence that hyperosmolar therapy (3% hypertonic saline and mannitol) may not improve intracranial pressure or cerebral perfusion pressure, or increase serum osmolarity, in children post TBI.

There is level 4 evidence that intracranial pressure can be lowered acutely (within 30 minutes) after 7.5% hypertonic saline treatment, for as long as 72 hours, using 3% hypertonic saline treatment in children refractory to standard therapy (intracranial pressure >20 mmHg) post TBI.

There is level 4 evidence that hypertonic saline treatment (3 or 7.5%) may increase cerebral perfusion pressure, serum sodium, and serum osmolarity in children refractory to standard therapy (intracranial pressure>20 mmHg) post TBI.

There is level 4 evidence that 7.5% hypertonic saline treatment is associated with hypernatremia, kidney injury, acute respiratory distress syndrome, and low Glasgow Outcome Scale- Extended score (3-4) in children refractory to standard therapy (intracranial pressure>20 mmHg) post TBI.

There is level 2 evidence that treatment of children with TBI following a new hypertonic saline-based protocol may increase favourable discharge disposition, but not Glasgow Outcome Scale scores, compared to therapy without guidance of a strict protocol.

There is level 4 evidence that early (<30 minutes post episode) hypotension treatment may reduce mortality compared to non-early hypotensive treatment in children post TBI.

There is level 4 evidence 3% hypertonic saline may decrease intracranial pressure and increase cerebral perfusion pressure faster than fentanyl (2μg/kg) and pentobarbital (5mg/kg) in pediatric patients post TBI.

There is level 4 evidence that high-dose fentanyl, low-dose midazolam, and high-dose fentanyl in combination with low-dose midazolam may increase intracranial pressure in pediatric patients post TBI.

There is conflicting (level 4) evidence regarding whether or not fentanyl reduces intracranial pressure and improves cerebral perfusion pressure in children following a severe TBI. 

There is level 4 evidence that pentobarbital may lower intracranial pressure and cerebral perfusion pressure in pediatric patients with refractory intracranial pressure post TBI.

There is level 1b evidence that amantadine may not improve level of consciousness (Coma/Near-Coma Scale, Coma Recovery Scale Revised, or Wee-FIM scores), but may improve blinded physicians’ ratings of consciousness, compared to placebo in pediatric patients post ABI.

There is level 1b evidence that an amantadine administration consisting of 4 mg/kg/d for a week followed by 6 mg/kg may be a safe and effective protocol compared to placebo in pediatric patients post ABI.

There is level 4 evidence that dopaminergic agents may increase responsiveness (Western NeuroSensory Stimulation Profile scores) in pediatric patients post ABI.

There is level 1a evidence that administration of dexamethasone may inhibit endogenous production of glucocorticoids compared to placebo in pediatric patients post TBI.

There is level 1b evidence that dexamethasone administration may not improve Glasgow Outcome Scale (GOS) scores, intracranial pressure, or blood pressure, but may increase the risk of bacterial pneumonia, compared to placebo in pediatric patients post TBI.

There is level 1b evidence that N-Acetylcysteine in combination with probenecid may increase N-Acetylcysteine levels in cerebrospinal fluid, but may not be different from placebo in its effect on intracranial pressure, temperature, Glasgow Outcome Scale (GOS) scores, hospital length of stay, or mean arterial pressure, in pediatric patients post TBI.

There is level 2 evidence that magnesium sulfate may not affect hemodynamics (intracranial pressure, cerebral perfusion pressure, mean arterial pressure) compared to placebo in children post TBI.

There is level 3 evidence that the presence of abusive head trauma, high PRISM III score, and low post-admission Glasgow Coma Scale scores, but not anemia and blood transfusions, are associated with increased mortality in pediatric patients post TBI.

There is level 4 evidence that coagulation assessments performed upon admission to a pediatric inpatient unit may be potential prognostic indicators of favourable outcomes post TBI.

There is level 4 evidence that a decompressive craniectomy may improve intracranial pressure and cerebral perfusion pressure in pediatric patients post TBI.

There is level 1b evidence that a decompressive craniectomy is as effective as standard intracranial pressure management at reducing intracranial pressure in pediatric patients post TBI.

There is level 4 evidence that a late decompressive craniectomy (< 2hr post admission) and intraoperative blood loss (>300 mL) are associated with greater mortality and worse outcomes in pediatric patients undergoing this procedure post TBI.

There is level 4 evidence that children with a severe TBI are at risk of secondary complications following a decompressive craniectomy that may prolong rehabilitation.

There is level 4 evidence that patients who undergo a decompressive craniectomy have greater Glasgow Outcome Scale scores than pediatric patients with TBI who do not.

There is level 3 evidence that children who sustain a severe TBI from non-accidental trauma have poorer outcomes and higher odds of mortality following a decompressive craniectomy, when compared to accidental trauma victims.

There is level 4 evidence that supraciliary “keyhole” small craniotomies for the treatment of anterior frontal space occupying lesions are not associated with major operative or post-operative complications in pediatric patients post ABI.

There is level 4 evidence that a burr-hole craniotomy without continuous drainage for the treatment of either a chronic subdural hematoma or a subdural hygroma is not associated with complications in pediatric patients post ABI.

There is level 3 evidence that there may be no difference in mortality between pediatric patients post TBI who were treated either at an adult or pediatric trauma center.

There is level 1b evidence that phenytoin prophylaxis may not reduce the occurrence of early (<1 week post injury) or late (>1 week post injury) post traumatic seizures compared to placebo in children post TBI.

There is level 4 evidence that children who develop early post traumatic seizures while receiving levetiracetam prophylaxis are younger and have experienced abusive head trauma, compared to those that did not develop post traumatic seizures.

There is level 1b evidence that the administration of enhanced immune formulas may not be superior to regular formulas in regards to increasing caloric and protein intake in children post TBI.

There is level 1b evidence that enhanced immune formulas may be superior to regular formulas at reducing markers of infection and inflammation (interleukin-8 concentrations and early gastric colonization) and improving 24 hour nitrogen balance in children post TBI.

There is level 1b evidence that initiating nutritional support earlier after ABI results in a decrease in mortality and better outcomes.

There is level 2 evidence that cognitive behavioral therapy may reduce anxiety, depression, and internalizing behaviour compared to no therapy in pediatric patients post ABI.

There is level 2 evidence that cognitive behavioural therapy may be more effective at improving socialization and internalizing behaviour in children post ABI who are not receiving adjunct pharmacotherapy, compared to those who are.

There is level 4 evidence that self-monitoring training can improve on-task behaviour, but not accuracy in completing assignments or task engagement, in children post TBI.

There is level 4 evidence that behavioural therapies for children with ABI may be effective in reducing or eliminating problematic behaviours, lowering agitation, and increasing autonomy.

There is conflicting (level 1b) evidence as to whether a counsellor-assisted problem-solving (CAPS) group is superior to an internet resource comparison intervention at improving management of externalizing, internalizing, and socialization behaviours in pediatric patients post TBI.

There is level 1b evidence that a counsellor-assisted problem-solving program may be superior to an internet resource comparison intervention at reducing conflict between parents and adolescents post TBI.

There is conflicting (level 1b) evidence as to whether lower or higher socioeconomic patients benefit most from a counsellor-assisted problem-solving intervention compared to an internet resource intervention post TBI.

There is level 1b evidence that treatment (counsellor-assisted problem-solving versus internet resource comparison), gender, race, age, or socioeconomic status do not affect use of mental health services in pediatric patients post TBI. 

There is level 1b evidence that an online problem-solving program with therapist assistance may not be superior to an internet resource comparison group at improving parent-teen communications and conflict post ABI.

There is level 1a evidence that an online problem-solving program with therapist assistance may be superior to an internet resource comparison group at improving compliant behaviour and self-management in children post TBI.

There is level 1a evidence that an online problem-solving program with therapist assistance may be superior to an internet resource comparison group at acutely improving anxiety, depression, and distress in the parents of children post ABI; however, only improvements in distress may be present at 18 months.

There is level 1a evidence that lower socioeconomic status is associated with greater reductions in distress and depressive symptoms following counsellor-assisted online therapy when compared to higher socioeconomic status in parents of children post ABI.

There is level 2 evidence that online problem solving with audio support may not be superior to the same program without audio support with regards to improving adolescent behavioural issues and depression in children post TBI.

There is level 1b evidence that an online parenting skills workshops (I-InTERACT) may improve positive parental involvement with their child, when compared with an internet resource group, in children post TBI.

There is level 1b evidence that an online parenting skills program (I-InTERACT) may not be superior to an internet resource comparison group at improving caregiver stress, distress, depression, and self-efficacy in individuals caring for children post TBI.

There is level 4 evidence that an app-based coaching intervention may increase confidence and participation frequency in pediatric TBI and brain tumor individuals.

There is level 2 evidence that the Stepping Stone Triple P program combined with Acceptance and Commitment Therapy may be superior to usual care at improving behavioural problems up to 6 months in children post ABI.

There is level 2 evidence that the Stepping Stone Triple P program combined with Acceptance and Commitment Therapy may improve parental distress, confidence, psychological flexibility, and conflict, but not depression, when compared to usual care in children post ABI.

There is level 2 evidence that face to face family problem solving therapy may be superior to usual care in terms of reducing internalizing problems (depression and anxiety) in children post TBI, but not parental distress or relationship satisfaction.

There is level 2 evidence that family-based therapy may be superior to standard clinician-directed care for improving intelligence, motor development, and functional independence in children post TBI.

There is level 4 evidence that a family focused inpatient social work program for parents/caregivers after their child’s TBI may not significantly decrease feelings of trauma or grief any more than a usual care intervention.

There is level 4 evidence that a family focused inpatient social work program for parents/caregivers after their child’s TBI may increase parent/caregiver confidence in managing the condition and feelings of more supportive counselling, increased family resources, and awareness of medical issues than a usual care intervention.

There is level 1b evidence that the allocation of community resource coordinators to a family post discharge may not be superior to standard care at improving functional outcomes in children following a TBI.

There is level 4 evidence that a multidisciplinary outpatient program may improve functional communication and behaviour, but not neuropsychological outcomes, in children post ABI.

There is level 1b evidence that family based online problem-solving programs, when compared to an internet resource comparison group, may improve functioning in school and the community, but not at home, at 12 months in adolescents post TBI.

There is level 4 evidence that interventions directed at strengthening the social interactions of children with brain injury may be temporarily beneficial.

There is level 2 evidence that a dedicated transitional hospital to school program does not demonstrate any increased benefits than a usual care group for children post TBI.

There is level 2 evidence that the use of amantadine can decrease the amount of aberrant behaviours, but may not improve cognitive functioning and problem solving, compared to usual care among children with a TBI.

There is level 3 evidence that amantadine is safe to administer in children following a TBI and facilitates rate of recovery, but not post-traumatic amnesia or hospital length of stay, post pediatric TBI.

There is level 1b evidence that the Amsterdam Memory and Training for children program may not improve sustained attention in pediatric patients post ABI compared an interactive program.

There is level 1b evidence that the Amsterdam Memory and Training for children may improve selective attention compared to an interactive program in pediatric patients post ABI.

There is level 2 evidence that the Attention Improvement and Management (AIM) program may improve sustained, but not selective, attention compared to healthy controls in children post TBI.

There is level 2 evidence that attention-specific neuropsychological training may improve attention compared to no training in pediatric patients post TBI.

There is level 2 evidence that a cognitive computerized training (CCT) program is feasible for use within a pediatric TBI population

There is conflicting (level 1b) evidence regarding whether or not methylphenidate improves cognitive behavioural function compared to placebo in children following a TBI.

There is level 2 evidence that the use of a pager system may improve memory and planning activities compared to having no pager system in adolescents post TBI.

There is level 4 evidence that rehabilitation focused around diary entries and self-instructional training may temporarily improve memory deficits in children post TBI.

There is level 2 evidence that sensory stimulation paired with cognitive neuropsychological rehabilitation may improve intellectual development in children with severe TBI compared to controls.

There is level 4 evidence that biweekly sessions of cognitive rehabilitation may improve memory skills in pediatric patients post TBI.

There is level 1a evidence that online counsellor-assisted problem solving programs may be superior to internet resource groups at improving executive function in adolescents post TBI.

There is level 1a evidence that older adolescents (14-17 years) benefit from counsellor-assisted problem solving programs more than younger (12-14 yr) adolescents in terms of improvements in executive functioning post TBI.

There is level 1b evidence that adolescents with a severe TBI, or poor vocabulary, benefit more from a counsellor-assisted problem solving program than adolescents with a moderate TBI, or adequate vocabulary, in terms of improvements in executive functioning post TBI.

There is level 1b evidence that the Strategic Memory Advanced Reasoning Training (SMART) program may improve higher-order cognitive deficits compared to bottom-up processing training in children post TBI.

There is level 1b evidence that metacognitive therapy may improve learning strategies and executive function compared to usual care in children and adolescents with an ABI.

There is level 4 evidence that the use of goal management therapy may improve parental ratings of executive function in young children who have sustained a TBI.

There is level 2 evidence that metacognitive problem-solving skills training may improve executive function and metacognitive abilities compared to no intervention in children post ABI.

There is level 4 evidence that electropalatography treatment may be effective at improving the articulatory component of dysarthria post TBI in children.

There is level 4 evidence that peer-group training of pragmatic language skills can improve pragmatic language behaviours and range of pragmatic communication abilities in children post ABI.

There is level 1b evidence that injury-related information interventions may not improve knowledge or awareness of injury-related deficits compared to placebo information sessions in children post TBI.

There is inconclusive (level 4) evidence regarding whether or not upper limb lycra splints improve the quality of movement in children post TBI.

There is level 2 evidence that constraint-induced movement therapy (CIMT) may improve motor function of the hemiparetic limb compared to no care in children post TBI.

There is level 2 evidence that walking and balance exercises performed in a virtual reality environment can improve pelvic and ankle kinematics, but not knee flexion, compared to healthy controls in children post ABI.

There is level 4 evidence that use of a Nintendo Wii console can improve motor coordination, as well as the amount and intensity of physical activity that a patient participates in, in children post ABI.

There is level 2 evidence that exoskeleton, body-weight supported treadmill training paired with physiotherapy may be superior to physiotherapy alone at improving gait and motor function in pediatric patients post ABI.

There is level 4 evidence that an wearable ankle robot combined with a computer game interface may be beneficial in reducing spasticity and increasing balance in children post ABI.

There is level 4 evidence that Robot Mediated Therapy (RMT) combined with goal-oriented reaching tasks may improve upper limb motor function and spasticity in children post ABI.

There is level 2 evidence that botulinum toxin type A (BTX-A) used in combination with adjunct therapy (physiotherapy, occupational therapy) may decrease upper and lower limb spasticity, as well as movement range of motion, in children and adolescents post ABI.

There is level 4 evidence that intrathecal baclofen pumps may be effective at reducing spasticity in the upper and lower limbs for children with ABI as a result of hypoxia.

There is level 1b evidence that home based exercise programs may be superior to regular daily activities at improving balance, dexterity, and aerobic capacity short-term (<6 weeks) in children post ABI.

There is level 1a evidence that the PURPLE intervention program may be effective for improving maternal knowledge of infant crying compared to an infant safety control group.

There is conflicting (level 1b) evidence regarding whether or not the PURPLE intervention program is effective at improving maternal knowledge of infant shaking, compared to an infant safety control group.

There is level 1a evidence that the PURPLE intervention program may be effective at improving maternal behaviours, such as walking away from an infant during inconsolable crying and sharing information on the dangers of shaken baby syndrome, compared to injury prevention educational materials.

There is level 4 evidence supporting the role of education programs for informing caregivers of children with shaken baby syndrome about its detrimental effects, helping parents change their behaviour, and reducing the number of shaken baby syndrome cases post intervention.

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