**2. Pathophysiology of pediatric TBI**

Brain damage in TBI may arise by two mechanisms, including (1) primary (immediate) injury, directly caused by mechanical forces during the initial insult, and (2) secondary (delayed) injury, accompanied by further tissue and cellular damages following primary insult. Primary injury occurs at the time of impact and is mostly irreversible. The immediate impact of different mechanical insults to the brain can cause two types of primary injuries: focal (brain contusions) and diffuse (diffuse axonal injury, diffuse vascular injury, edema). However, the common coexistence of focal and diffuse injuries in patients suffered from moderate to severe TBI was demonstrated [4, 5].

Secondary damages to the brain occur after the initial impact. This is initial injury progression in delayed and prolonged manner, lasting from hours to many years. There are number of factors contributing to secondary injuries, which include hypoperfusion of the penumbral region surrounding the primary injury, excitotoxicity, mitochondrial dysfunction, oxidative stress, lipid peroxidation, edema, neuroinflammation, axonal degeneration and apoptotic cell death [6, 7]. Depending on the age when the TBI happens, the effects of secondary injuries will vary, altering a variety of biological processes of brain development, including myelination, neurotransmitter and neurotrophin development, synaptogenesis and synaptic reorganization, gliogenesis, programmed cell death, blood-brain barrier function and cerebrospinal fluid dynamics. The secondary injury is believed to be an important determinant of outcomes and it may be preventable and more responsive to appropriate and timely medical intervention.

Defining the severity of TBI in the acute period is important as it is predictive of the outcome. The periodization of TBI clinical course could be delineated as follows [8], depending on its initial severity:

1.The acute period lasting 2–10 weeks.

2.The intermediate (subacute) period, from 10 weeks to 6 months post-injury.

3.The long-term (chronic) period, from 6 months to up to 2 years or more.

The factors, defining the long-term impact of TBI on the individual functioning include:

**187**

*Neurobehavioral, Cognitive, and Paroxysmal Disorders in the Long-Term Period of Pediatric…*

The localization of damage for particular types of TBI is rather typical [9]. For instance, the areas predominantly affected by contusions are the frontal and temporal lobes as well as the brain stem—regions located near bony prominences. Brain regions particularly involved in diffuse axonal (or shearing) injury are the corpus

However, not only the severity of TBI, but also the age at which it occurred, has a significant impact on the clinical manifestations of the consequences of TBI. Research on the response of children's brains to TBI has led to important results on the impact of age on recovery from injury and its functional consequences, and

were any long-term sequelae from such injuries. The prevailing view was that as children's brains are more plastic and better able to accommodate the effects of brain insults, children would experience fewer deficits than adults. The developing brain is capable of more significant reorganization and recovery after TBI. In addition, after damage to immature brain, progressive cognitive decline is less likely to develop, and ongoing neurodevelopment may contribute to recovery [10]. Most skills formed by the time of injury are preserved, even if they were temporarily lost or compromised [9]. As a result, children are more likely than adults to have a favorable outcome, even

after severe TBI, due to the high neuroplasticity of the developing brain.

On the other hand, studies of Klonoff et al. [11, 12] and Rutter et al. [13] and some others have shown that TBI in childhood does have measurable consequences in terms of functional impairment. Another concept was formulated considering the developing brain as more vulnerable to TBI if it is affected during critical periods of significant growth, formation of brain circuits and functions, which may lead to more serious and persistent physiological changes after a TBI. Brain structures and functions that continue to mature at the time of TBI may be affected to a greater extent than those formed before the injury [14]. Thus, the age of TBI is an important

Many children who suffered TBI make a good physical recovery and appear outwardly normal. However, even after mild TBI, children may continue to experience problems when faced with the complexities of everyday life, particularly learning, skill acquisition, cognitive and psychosocial functioning [15, 16]. Thus, even a mild TBI suffered in childhood does not always pass without a trace, and its

Educational and behavioral developments as well as social adaptation are dependent upon the intact capacities of learning, attention, and executive functioning (EF). Many of these skills are impaired as a result of TBI, even while intellectual functioning, as measured by traditional psychometric tests, may appear intact [17].

Early studies of childhood TBI were largely directed at determining whether there

*DOI: http://dx.doi.org/10.5772/intechopen.93733*

b.localization of damage

d.the functions affected

a.the severity of the initial injury in the acute period

c.the rate and completeness of physiological recovery

e.the meaning of the dysfunction to the individual

callosum, subcortical white matter and the mid-brain.

f. functions which are not affected by TBI

g.the resources available to aid recovery.

various opinions have been formulated.

factor influencing its consequences.

consequences can manifest years after the injury.

*Neurobehavioral, Cognitive, and Paroxysmal Disorders in the Long-Term Period of Pediatric… DOI: http://dx.doi.org/10.5772/intechopen.93733*


*Advancement and New Understanding in Brain Injury*

tion and high neuroplasticity of the developing brain.

sive to appropriate and timely medical intervention.

[8], depending on its initial severity:

1.The acute period lasting 2–10 weeks.

**2. Pathophysiology of pediatric TBI**

TBI was demonstrated [4, 5].

and depends on the age of impact, influencing different stages of brain development. TBI interferes with the normal course of neuroontogenesis, disturbing the development of cognitive functions, school education, behavior, and social skills formation. Cognitive and behavioral disorders in children and adolescents in the long-term period of TBI are significantly increased in the presence of paroxysmal disorders: post-traumatic headache, post-traumatic epilepsy, subclinical epileptiform activity on the EEG. Therapeutic and rehabilitation measures in the long-term period of TBI in children and adolescents should be intensively carried out both in the first 12 months after TBI, when the most significant results from their use are expected, and in the long-term period, considering the ongoing processes of morpho-functional matura-

Despite the importance of the problem, there is no specific treatment for the long-term consequences of childhood TBI, and the available recommendations are mostly extrapolated from studies conducted on adult patients, and thus do not take into account the features of the child's neurodevelopment and brain plasticity [2, 3].

Brain damage in TBI may arise by two mechanisms, including (1) primary (immediate) injury, directly caused by mechanical forces during the initial insult, and (2) secondary (delayed) injury, accompanied by further tissue and cellular damages following primary insult. Primary injury occurs at the time of impact and is mostly irreversible. The immediate impact of different mechanical insults to the brain can cause two types of primary injuries: focal (brain contusions) and diffuse (diffuse axonal injury, diffuse vascular injury, edema). However, the common coexistence of focal and diffuse injuries in patients suffered from moderate to severe

Secondary damages to the brain occur after the initial impact. This is initial injury progression in delayed and prolonged manner, lasting from hours to many years. There are number of factors contributing to secondary injuries, which include hypoperfusion of the penumbral region surrounding the primary injury, excitotoxicity, mitochondrial dysfunction, oxidative stress, lipid peroxidation, edema, neuroinflammation, axonal degeneration and apoptotic cell death [6, 7]. Depending on the age when the TBI happens, the effects of secondary injuries will vary, altering a variety of biological processes of brain development, including myelination, neurotransmitter and neurotrophin development, synaptogenesis and synaptic reorganization, gliogenesis, programmed cell death, blood-brain barrier function and cerebrospinal fluid dynamics. The secondary injury is believed to be an important determinant of outcomes and it may be preventable and more respon-

Defining the severity of TBI in the acute period is important as it is predictive of the outcome. The periodization of TBI clinical course could be delineated as follows

2.The intermediate (subacute) period, from 10 weeks to 6 months post-injury.

The factors, defining the long-term impact of TBI on the individual functioning

3.The long-term (chronic) period, from 6 months to up to 2 years or more.

**186**

include:


The localization of damage for particular types of TBI is rather typical [9]. For instance, the areas predominantly affected by contusions are the frontal and temporal lobes as well as the brain stem—regions located near bony prominences. Brain regions particularly involved in diffuse axonal (or shearing) injury are the corpus callosum, subcortical white matter and the mid-brain.

However, not only the severity of TBI, but also the age at which it occurred, has a significant impact on the clinical manifestations of the consequences of TBI. Research on the response of children's brains to TBI has led to important results on the impact of age on recovery from injury and its functional consequences, and various opinions have been formulated.

Early studies of childhood TBI were largely directed at determining whether there were any long-term sequelae from such injuries. The prevailing view was that as children's brains are more plastic and better able to accommodate the effects of brain insults, children would experience fewer deficits than adults. The developing brain is capable of more significant reorganization and recovery after TBI. In addition, after damage to immature brain, progressive cognitive decline is less likely to develop, and ongoing neurodevelopment may contribute to recovery [10]. Most skills formed by the time of injury are preserved, even if they were temporarily lost or compromised [9]. As a result, children are more likely than adults to have a favorable outcome, even after severe TBI, due to the high neuroplasticity of the developing brain.

On the other hand, studies of Klonoff et al. [11, 12] and Rutter et al. [13] and some others have shown that TBI in childhood does have measurable consequences in terms of functional impairment. Another concept was formulated considering the developing brain as more vulnerable to TBI if it is affected during critical periods of significant growth, formation of brain circuits and functions, which may lead to more serious and persistent physiological changes after a TBI. Brain structures and functions that continue to mature at the time of TBI may be affected to a greater extent than those formed before the injury [14]. Thus, the age of TBI is an important factor influencing its consequences.

Many children who suffered TBI make a good physical recovery and appear outwardly normal. However, even after mild TBI, children may continue to experience problems when faced with the complexities of everyday life, particularly learning, skill acquisition, cognitive and psychosocial functioning [15, 16]. Thus, even a mild TBI suffered in childhood does not always pass without a trace, and its consequences can manifest years after the injury.

Educational and behavioral developments as well as social adaptation are dependent upon the intact capacities of learning, attention, and executive functioning (EF). Many of these skills are impaired as a result of TBI, even while intellectual functioning, as measured by traditional psychometric tests, may appear intact [17].

In general, a favorable outcome is possible in children more often than adults even after severe TBI. Nevertheless, neurological, cognitive, behavioral, emotional, and socio-psychological consequences can be observed in the long-term period of TBI in children and adolescents. The complexity of pediatric TBI is due to the heterogeneity of its pathophysiology and depends on the age of impact, influencing different stages of brain development.
