**5. Pathophysiology**

TBI pathogenesis involves primary and secondary injuries culminating in a temporary or permanent neurological deficit. Primary injury represents brain dysfunction as a direct result of brain deformation. Structural damage in focal, multifocal, or diffuse pattern in primary injury can only be prevented before the collision. Consequent molecular, chemical, and inflammatory cascades further extend the reversible secondary injury from minutes to days after the primary insult [18].

Theoretically, cerebral blood flow (CBF) and therefore, cerebral perfusion pressure (CPP) is determined by the difference between mean arterial pressure (MAP) and ICP. It is noteworthy that in TBI cases, studies demonstrated that the cerebral autoregulation mechanism impairment in the presence of normal CBF and CPP values. Decreased metabolic demand in coma or ischemic conditions may be the plausible explanation for cerebral hypoperfusion after TBI. Under such pathophysiologic conditions, CBF continues to decline to reach ischemic level thus exacerbating the impact of secondary injury [19]. CBF restoration may also cause reperfusion injury mediated by oxidative stress, leukocyte infiltration, and blood brain barrier dysfunction [20, 21].

Deterioration of CBF deprives the cells of their metabolic needs and forcing them to switch into anaerobic metabolism. Less energy and more lactate production in anaerobic metabolism give rise to failure in cellular functioning and generate an acidic milieu [20]. Moreover, the glial-neuronal uncoupling further enhances extracellular lactate production independent of ischemia, resulting in lactate storm in severe cases [22].

One of the main concern in the cerebral metabolic alteration is the failure of the sodium/potassium (Na/K) pumps. Massive sodium influx precipitates the cascades in secondary injury through neuron depolarization. Depolarized neurons release excitatory neurotransmitters, including glutamate and aspartate, which leads to intracellular calcium increase and enzymes and free radicals activation [20, 22, 23]. Neuronal cells degradation triggers neuroimmune responses and instigates BBB dysfunction, both of which add up to the cerebral edema progression [23, 24]. Vasogenic and cytotoxic edema in TBI is followed by raised ICP. According to the Monro-Kellie doctrine, the brain responds to the edema by displacing CSF and venous blood away. Failure of this compensation mechanism ultimately results in brain compression and death [20, 23].

## **6. Diagnosis and clinical manifestations**

Amidst many classification systems and scales constructed for TBI diagnosis, this review focuses on definition generalizability since some recent studies focused solely on sports-related concussion. Disease severity is classified into mild, moderate, and severe based on GCS level and imaging findings.

#### **6.1 Mild TBI**

The mildest form of TBI, or concussion, conversely raises considerable concern because of its large proportion and rather unsettled recognition approach. This mild manifestation can coexist in more severe TBI cases. Despite vast heterogeneity in definitions provided, the common ground is that the patient is alert and experiencing any of the mild TBI clinical phenotypes after head injury. As observed in **Table 2**, no clear-cut definition for concussion and loss of consciousness alone is not a prerequisite in defining concussion. Some organizations focus on the clinical criteria, while others incorporate validated supplementary tools to objectify the assessment.

The most specific and systematic clinical criterias are provided by the Brain Trauma Foundation (BTF) [4] and Craton et al. [27] based on Concussion in Sport Group (CISG) guidelines. BTF clearly defined the clinical indicators and assigned specific time intervals for each in the first step of its guideline [4], whereas the second step of the guideline described clinical concussion subtypes and associated conditions [28]. Craton et al. on the other hand classified the symptoms into seven

**91**

(PECARN) decision rules.

*Proposed definitions of concussion.*

**6.2 Moderate and severe TBI**

*Traumatic Brain Injury in Children*

Diagnostic criteria

Supporting tool

Exclusion requirement

Noncontributing factors

**Table 2.**

*DOI: http://dx.doi.org/10.5772/intechopen.96010*

Alteration in memory and orientation

PCSS, GSC, SAC

CT imaging in select cases

clinical phenotypes with *COACH CV* mnemonics and suggested specific testings in

*AAN, American Academy of Neurology; BMI, body mass index; BTF, Brain Trauma Foundation; CDC, Centers for Disease Control and Prevention; CISG, Concussion in Sport Group; CT, computed tomography; GCS, Glasgow Coma Scale; GSC, Graded Symptom Checklist; HBI, Health and Behavior Inventory; LOC, loss of consciousness; NINDS, National Institute of Neurological Disorders and Stroke; PCSI, Post-Concussion Symptom Inventory; PCSS, Post-Concussion Symptom Scale; PECARN, Pediatric Emergency Care Applied Research Network; SAC,* 

**AAN [25] BTF [4] CDC [26] CISG [7] NINDS [2]**

Symptoms, signs, balance impairment, behavioral changes, cognitive impairment, sleep/wake disturbance

SCAT5, SAC

Clinical utility of advanced neuroimaging requires further validation

LOC

LOC, headache, confusion, lightheadedness, dizziness, blurred vision, tinnitus, change in sleep patterns, behavioral or mood changes, and impaired memory, concentration, attention, or thinking

Confusion or disorientation, posttraumatic amnesia, focal signs, symptoms, or seizure

GSC, PCSS, HBI,

or neurosurgical intervention requirement

CT imaging in select cases (PECARN)

PCSI

GCS — 13–15 13–15 ≥ 30 minutes — —

Disorientation or confusion, impaired balance, slower reaction time, impaired verbal learning and memory

Supporting tools proposed by the guidelines are meant as a diagnostic adjunct to clinical indicators. The tools are validated and mentioned in the order of their priority as in the actual guideline. Each tool is age- and condition-specific, therefore careful consideration should be taken before administering and interpreting the results in decision making strategy. Computed tomography (CT) scan is indicated in select cases when more severe TBI or complication is suspected or as suggested by intermediate or high risk in Pediatric Emergency Care Applied Research Network

Detecting moderate and severe TBI cases are more straightforward with commonly accepted classification based on the level of consciousness measured in pediatric Glasgow Coma Scale (GCS) [29] and evidence of pathological imaging findings. GCS level lower than 9 is considered severe TBI, while GCS level within the range of 9–13 is considered moderate TBI. Based on anatomical structure

addition to supplementary tools for identifying each phenotype [27].

*Standardized Assessment of Concussion; SCAT5, Sports Concussion Assessment Tool version 5.*

LOC Hospitalization


*Advancement and New Understanding in Brain Injury*

dysfunction [20, 21].

in severe cases [22].

**6.1 Mild TBI**

assessment.

brain compression and death [20, 23].

**6. Diagnosis and clinical manifestations**

ate, and severe based on GCS level and imaging findings.

Theoretically, cerebral blood flow (CBF) and therefore, cerebral perfusion pressure (CPP) is determined by the difference between mean arterial pressure (MAP) and ICP. It is noteworthy that in TBI cases, studies demonstrated that the cerebral autoregulation mechanism impairment in the presence of normal CBF and CPP values. Decreased metabolic demand in coma or ischemic conditions may be the plausible explanation for cerebral hypoperfusion after TBI. Under such pathophysiologic conditions, CBF continues to decline to reach ischemic level thus exacerbating the impact of secondary injury [19]. CBF restoration may also cause reperfusion injury mediated by oxidative stress, leukocyte infiltration, and blood brain barrier

Deterioration of CBF deprives the cells of their metabolic needs and forcing them to switch into anaerobic metabolism. Less energy and more lactate production in anaerobic metabolism give rise to failure in cellular functioning and generate an acidic milieu [20]. Moreover, the glial-neuronal uncoupling further enhances extracellular lactate production independent of ischemia, resulting in lactate storm

One of the main concern in the cerebral metabolic alteration is the failure of the sodium/potassium (Na/K) pumps. Massive sodium influx precipitates the cascades in secondary injury through neuron depolarization. Depolarized neurons release excitatory neurotransmitters, including glutamate and aspartate, which leads to intracellular calcium increase and enzymes and free radicals activation [20, 22, 23]. Neuronal cells degradation triggers neuroimmune responses and instigates BBB dysfunction, both of which add up to the cerebral edema progression [23, 24]. Vasogenic and cytotoxic edema in TBI is followed by raised ICP. According to the Monro-Kellie doctrine, the brain responds to the edema by displacing CSF and venous blood away. Failure of this compensation mechanism ultimately results in

Amidst many classification systems and scales constructed for TBI diagnosis, this review focuses on definition generalizability since some recent studies focused solely on sports-related concussion. Disease severity is classified into mild, moder-

The mildest form of TBI, or concussion, conversely raises considerable concern because of its large proportion and rather unsettled recognition approach. This mild manifestation can coexist in more severe TBI cases. Despite vast heterogeneity in definitions provided, the common ground is that the patient is alert and experiencing any of the mild TBI clinical phenotypes after head injury. As observed in **Table 2**, no clear-cut definition for concussion and loss of consciousness alone is not a prerequisite in defining concussion. Some organizations focus on the clinical criteria, while others incorporate validated supplementary tools to objectify the

The most specific and systematic clinical criterias are provided by the Brain Trauma Foundation (BTF) [4] and Craton et al. [27] based on Concussion in Sport Group (CISG) guidelines. BTF clearly defined the clinical indicators and assigned specific time intervals for each in the first step of its guideline [4], whereas the second step of the guideline described clinical concussion subtypes and associated conditions [28]. Craton et al. on the other hand classified the symptoms into seven

**90**


*AAN, American Academy of Neurology; BMI, body mass index; BTF, Brain Trauma Foundation; CDC, Centers for Disease Control and Prevention; CISG, Concussion in Sport Group; CT, computed tomography; GCS, Glasgow Coma Scale; GSC, Graded Symptom Checklist; HBI, Health and Behavior Inventory; LOC, loss of consciousness; NINDS, National Institute of Neurological Disorders and Stroke; PCSI, Post-Concussion Symptom Inventory; PCSS, Post-Concussion Symptom Scale; PECARN, Pediatric Emergency Care Applied Research Network; SAC, Standardized Assessment of Concussion; SCAT5, Sports Concussion Assessment Tool version 5.*

#### **Table 2.**

*Proposed definitions of concussion.*

clinical phenotypes with *COACH CV* mnemonics and suggested specific testings in addition to supplementary tools for identifying each phenotype [27].

Supporting tools proposed by the guidelines are meant as a diagnostic adjunct to clinical indicators. The tools are validated and mentioned in the order of their priority as in the actual guideline. Each tool is age- and condition-specific, therefore careful consideration should be taken before administering and interpreting the results in decision making strategy. Computed tomography (CT) scan is indicated in select cases when more severe TBI or complication is suspected or as suggested by intermediate or high risk in Pediatric Emergency Care Applied Research Network (PECARN) decision rules.
