Traumatic brain injury (TBI) is classified as one of a diverse group of sterile injuries that can give rise to cell death, inflammation, and neurologic dysfunction in patients independent of age, sex and race.

TBI is complex and has proven particularly challenging to diagnose and treat. [1]
 

The absence of imaging findings to support the conclusion of brain trauma is not necessarily a pathognomonic of a non-traumatized brain. In many cases, structural neuroimaging (MRI) immediately following the injury remain normal. [2] Often, even in young people with prolonged post-concussion symptoms, no abnormality on imaging is demonstrated. [3] There is an ever growing support in the literature that “many brain injuries are likely go undetected on any imaging modality in current use”. [4]
 

Severe single incident injuries, even without skull fracture may lead to permanent brain damage with incomplete recovery, with residual sensory, motor, and cognitive deficits and post-traumatic stress disorders frequently accompanying the TBI. [5]
 

Both temporal and subcellular abnormalities may be delayed following TBI and white and grey matter destruction may remain undiscovered. [6] A myriad of neurologic symptoms and deficits, including headaches, fatigue, vision, balance, coordination, concentration,

confusion, dizziness, insomnia, nausea and other autonomic system dysfunctions may occur.

These symptoms are all commonly noted as post-concussion sequelae. [7]

Neuroinflammation following TBI, in the acute stage, occurs due to cell death, is a contributing factor in post-concussion headache and is anti-inflammatory resistant. More importantly, it has been linked to the long-term development of neurodegenerative diseases. [10] In animal studies, post-TBI inflammation is not limited only to the damaged site, but spreads to remote areas of the brain as well. [11] Chronic neuroinflammation is linked to debilitating, post-traumatic headache (PTHAs). [12]
 

Changes in emotion are frequent and common corollaries of severe brain injury. [21] There is a growing trend to include “emotional TBI” into the TBI definition. Synaptic plasticity changes, due to brain injury, elevate brain stress, hormones, reduce neurogenesis and lead to dendritic atrophy and impaired cognition. [22]

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