Primary etiologies of acute brain injury in children include traumatic brain injury (TBI), hypoxic-ischemic encephalopathy (HIE), stroke, cerebral hemorrhages, infections, inflammatory conditions, seizures, tumor or mass lesions, metabolic abnormalities, and toxins (Table 105-1). TBI is the leading cause of death and disability in both children older than 1 year of age and young adults. Following the primary injury, the tissues surrounding the injury and the entire brain are vulnerable to further secondary injuries. The purpose of the initial management, investigation, monitoring, and treatment of acute brain injuries is aimed at preventing this secondary injury.
TABLE 105-1ETIOLOGIES OF ACUTE BRAIN INJURY |Favorite Table|Download (.pdf) TABLE 105-1ETIOLOGIES OF ACUTE BRAIN INJURY
| Focal parenchymal contusion |
| Diffuse axonal injury |
| Intracranial hemorrhage |
|Hypoxic-ischemic encephalopathy |
| Severe shock |
| Cardiac arrest |
| Asphyxia (drowning, strangulation) |
| Cellular dysoxia (cyanide poisoning) |
|Central nervous system infection |
|Inflammatory, autoimmune, postinfectious |
|Mass lesions |
| Tumor |
| Hydrocephalus |
| Arterial infarction |
| Cerebral venous thrombosis |
| Vasculitis |
|Status epilepticus |
|Metabolic abnormalities |
Pathophysiology of Secondary Injuries
Secondary injuries evolve in the minutes to days after the primary event and include both endogenous responses to the primary injury and secondary insults that occur in the field or during the course of care, such as hypoxemia or hypotension. Mechanisms involved in endogenous secondary injuries include energy failure, excitotoxicity and apoptosis, oxidative stress, mitochondrial dysfunction, inflammation, and multiple cell death pathways.
Hypoxia-Ischemia, Energy Failure, Excitotoxicity, and Oxidative Stress
In severe injury with cessation of blood flow, as occurs in ischemic stroke or cardiac arrest, a characteristic pattern of injury ensues. Oxygen stores are depleted very rapidly (< 20 seconds), and adenosine triphosphate (ATP) stores are depleted within 5 minutes. No further ATP can be generated to fuel energy-dependent cellular processes, and cell membranes depolarize, resulting in influx of sodium and calcium, efflux of potassium, cellular swelling, oxygen free radical production, and release of excitatory neurotransmitters such as glutamate from astrocytes and neurons. The release of glutamate triggers further depolarization of adjacent cells, and this potent combination of increased cellular metabolism and ischemia accelerates hypoxic injury. The same cellular dysfunction also occurs in situations of altered blood flow and is demonstrated in TBI, status epilepticus, and meningitis. In adult studies, cerebral blood flow (CBF) of less than 55 mL/100 g/min of brain tissue (at normothermia) led to inhibition of protein synthesis, key to the regeneration of injured tissues. CBF of less than 20 mL/100 g/min resulted in anoxic depolarization. These thresholds are likely higher in injured brain tissue, rendered vulnerable by excitotoxicity, seizures, and impaired oxygen utilization from mitochondrial dysfunction. Either globally or more focally, disturbance to the neurovascular unit that regulates CBF occurs in all forms of severe acute brain injury as a consequence of direct tissue disruption, edema, intracranial hypertension, vasospasm and loss of autoregulation. Much of the secondary injury in severe TBI and meningitis is hypoxic-ischemic in nature.
Necrosis and Programed Cell Death
Energy failure, excitotoxicity, and oxidative stress are the principle mechanisms leading to cell death, which can take the form of necrosis or apoptosis. The age of the child (ie, maturity), the severity and duration of the primary and secondary insults, and the vulnerability of the brain region contribute differently to determining the vulnerability or the resilience of the tissue. In circumstances of severe injury, the most vulnerable brain regions are the watershed areas of the intervascular boundary zones and areas with the highest metabolic rate, such as the thalami, basal ganglia, and sensorimotor cortex.
Cerebral edema in acute brain injury peaks at 24 to 72 hours after the initial insult and can result from three mechanisms: astrocyte and neuronal swelling, vasogenic edema, and osmolar swelling. Vasogenic edema results from inflammation and disruption of the blood–brain barrier (BBB) with endothelial dysfunction, such as in meningoencephalitis. Osmolar swelling occurs when intracellular macromolecules degrade, thus increasing intracellular osmolarity and drawing in of water.
The complications of acute brain injury can be focal and/or global. Focal neuroanatomical deficits are revealed on clinical examination with functional assessments (eg, Pediatric ...