Traumatic brain injury (TBI) is a form of acquired brain injury that occurs when a sudden trauma causes damage to the brain.
TBI is the commonest cause of coma and the leading cause of death in those under 45.
300-400 per 100,000 in high income countries REF
Large global variation 60 to 811 per 100 000
Incidence increasing in low income countries with increased road usage and lower safety standards
Incidence increasing in high income countries due to falls in elderly patients
Australian figures are 275 per 100,000 REF
This compares with aSAH c.10/100000, ICH c.10/100000 person years, AIS c.100/100,000
Globally 69 million individuals are estimated to suffer TBI from all causes each year REF
Incidence peaks in the 0-4 year olds, young men and then significantly in the elderly:
CLASSIFICATION
There are several ways to classify TBI.
All give some idea about prognosis.
Understanding the pathophysiology of Secondary Brain Injury is most useful in terms of critical care management.
MILD: GCS 14-15 (81%)
MOD: GCS 9-13 (11%)
SEVERE: GCS 3-8 (8%)
Direct Impact
Penetrating injury
Rapid acceleration and deceleration
Blast Injury
Often the focus of the SURGICAL MANAGEMENT
Affects prognosis
FOCAL PATHOLOGY
> Extradural haematoma (EDH)
> Subdural haematoma (SDH)
> IntraCerebral Haemorrhage (ICH) AKA haemorrhagic contusion AKA intraparenchymal haematoma
> Subarachnoid haemorrhage (SAH)
> Intra-ventricular haemorrhage (IVH)
NON-FOCAL PATHOLOGY
> Global ischaemia
> Diffuse Axonal Injury
> Diffuse brain swelling
> Post-traumatic hydrocephalus
PRIMARY BRAIN INJURY
Injuries caused by the trauma, causing neuronal ischaemia and death
Determined by the initial impact so can’t really be influenced by what we do
SECONDARY BRAIN INJURY
> The focus of the critical care management
> Because some causes are modifiable
SYSTEMIC
> Hypoxia
> Hypo- and hypercapnoea
> Hyperthermia (fever)
> Hypo- and hyperglycaemia
> Hypo- and hypernatraemia
> Hyperosmolality
> Non-CNS infection / sepsis
INTRACRANIAL
> Seizures
> Delayed bleed / haematoma
> Effects of SAH
> Vasospasm
> Hydrocephalus
> CNS infection
> Paroxysmal sympathetic hyperactivity
CLINICALLY RELEVANT PATHOPHYSIOLOGY
> The brain is enclosed within the rigid skull and dura
> Small increases in intracranial volume result in sharp increases in intracranial pressure: The Monroe-Kelly doctrine
See section on EICP Fundamentals
> TBI invokes and inflammatory response characterised by the release of pro- and anti-inflammatory mediators
> This response alters the permeability of the blood-brain barrier (BBB), causes glial swelling and alters global and regional cerebral blood flow
> Altered BBB permeability can change response to IV fluids, osmotic diuretics and vasoactive drugs
Normally, cerebral perfusion is maintained at a constant rate in the presence of changing perfusion pressures by regional myogenic and metabolic autoregulation
When these mechanisms are damaged in TBI 3 patterns of cerebral blood flow (CBF) follow:
These are generalised phenomena that are seen, and there is significant variation between patients
This is covered in the Elevated Intracranial Pressure Module
TBI is the classic model for EICP and the principles described there all apply to severe TBI patients.
Secondary injury mechanisms include:
- Excitotoxicity
- Calcium influx
- Oxidative injury (through lipid peroxidation, protein nitrosylation, and DNA damage)
- Cellular and humoral inflammatory mediators
- Energy failure
Which result in secondary neuronal loss through a range of cell death modes (necrosis, apoptosis, necroptosis, paraptosis, parthanosis, autophagy, and phagoptosis of injured but viable cells by activated microglia).
Cytotoxic edema may arise from either reduced energy supply or increased energy demand.
Systemic hypoxia and hypotension are important causes of inadequate oxygen and substrate delivery, and powerful modulators of outcome
Even if systemic physiology is maintained, classic ischemia is seen, commonly within the first 24 hours after TBI and often in relation to contusions and SDHs.
Other factors that impair energy generation include:
- Tissue hypoxia arising from impaired oxygen diffusion
- Microvascular ischemia
- Mitochondrial dysfunction causing metabolic crisis
Mitochondrial dysfunction may be due to mechanical disruption of mitochondria, or due to competitive inhibition in the respiratory chain by elevated levels of nitric oxide.
These energy crises can be measured locally with cerebral microdialysis, a form of invasive neuromonitoring used mainly in research centres.
Cortical spreading depression (CSD) is increasingly recognised pathologic process following TBI
CSD is a physiologic phenomenon characterized by transient cortical gray matter depolarization that expands to adjacent regions at a rate of 2–5 mm/min, resulting in suppression of spontaneous electrical activity for a period of several minutes.
Detectable on electroencephalography, this “silencing” of brain activity is thought to underlie the metabolic disruption and redistribution of ions characteristic of CSD.
This includes neuronal K+ efflux and Ca2+ influx, glutamatergic neurotransmission, and astrocyte-mediated cerebral blood flow (CBF) modulation.
The ensuing metabolic crisis ultimately contributes to the delayed secondary insults following TBI.
With improvements in electrocorticography (ECoG) and intracranial electroencephalography approaches, real-time cortical monitoring has become more clinically feasible.
Further understanding CSD in TBI may provide a new treatment paradigm in managing TBI. REF
More on CSDThere is good evidence that an individual’s genetics affect their recovery following TBI.
There are many challenges to examining the genetic basis of recovery from brain injury in humans, and the results of many studies performed to date are not really conclusive.
BDNF and APOE gene loci have been thought to be involved in recovery from TBI or stroke
Genome wide Association Studies have not confirmed this however but have brought forward new candidates that require validation and further analysis.
A complicated and developing area of research. Read more here.