Traumatic Brain Injury (TBI)

Primer

Traumatic Brain Injury (TBI) is an intracranial injury that occurs when an external force injures the brain. When clinically significant, the DSM-5 diagnoses are major neurocognitive disorder or mild neurocognitive disorder due to Traumatic Brain Injury.[1]

Epidemiology
  • About 2% of the population lives with TBI-associated disability.
  • Males account for the majority of TBI cases. The leading causes of TBI are due to falls, motor vehicle accidents, contact sports, and assaults.[2]
  • There are three peak mean ages of highest TBI incidence, including 0–4 years, 15–19 years, and over 65 years.[3]
Prognosis
  • Neuropsychiatric symptoms tend to be most severe in the first few months following a TBI.
    • In mild-moderate TBI, the typical course is complete or substantial improvement of neuropsychiatric symptoms.
      • Approximately 80% of all TBIs are of mild severity.[4]
      • The symptoms associated with mild TBI resolve within days to weeks after the injury, with complete resolution typical by 3 months.
      • Neuropsychiatric symptoms such as depression, irritability, fatigue, headache, photosensitivity, sleep disturbance also tend to resolve in the weeks following mild TBI.
  • In moderate-to-severe TBI, seizures (particularly in the first year), photosensitivity, and hyperacusis can remain.
    • Neuropsychiatric symptoms such as irritability, aggression, depression, sleep disturbance, fatigue, and apathy can occur.
    • These changes can lead to significant psychosocial impairment compared to the pre-injury level, and deterioration in interpersonal relationships.
    • Moderate and severe TBI are associated with increased risk of depression, PTSD, aggression, and possibly neurodegenerative diseases such as Alzheimer's disease.
Older Adults
  • Those aged >75 years have the highest incidence of TBI of any group.[5]
  • The most common mechanism of injuries are falls from standing height and motor vehicle accidents. In this older cohort, women are affected more than men. There is an increased risk of intracranial bleeding (even in those with mild TBIs).
  • Older adults generally also have higher morbidity and mortality, slower recovery, and worse functional outcomes.[6]
  • The impairment in cognitive domains post-TBI may improve within the first 6 to 12 months, but keeping an age-related dementia on the differential diagnosis is important.
  • Additionally, the increased frequency of pre-existing and co-morbid medical conditions make TBI outcome assessments challenging, and it can be hard to isolate the effect of the TBI alone.
  • Though age is an important prognostic factor for recovery in TBI, it is not the sole determining factor. Older adults with TBI can have similar outcomes as their younger cohorts.[7]
Comorbidity
  • Individuals post-TBI have a higher chance of developing depression and posttraumatic stress disorder (PTSD).[8]
  • Although substance use disorders can high before the onset of a TBI, it in fact declines after injury.[9]
  • In those with a trauma history related to the TBI, subsequent PTSD can have symptoms such as anxiety, irritability, insomnia, personality changes, and memory problems, and this overlap can sometimes complicate the diagnostic picture.[10]

DSM-5 Diagnostic Criteria

Criterion A

The criteria are met for major or mild neurocognitive disorder

Criterion B

There is evidence of a traumatic brain injury—that is, an impact to the head or other mechanisms of rapid movement or displacement of the brain within the skull, with one or more of the following:

  1. Loss of consciousness.
  2. Posttraumatic amnesia.
  3. Disorientation and confusion.
  4. Neurological signs (e.g. - neuroimaging demonstrating injury; a new onset of seizures; a marked worsening of a preexisting seizure disorder; visual field cuts; anosmia (loss of smell); hemiparesis).
Criterion C

The neurocognitive disorder presents immediately after the occurrence of the traumatic brain injury or immediately after recovery of consciousness and persists past the acute post-injury period.

Terminology

Concussions

Concussions can be considered a form of mild traumatic brain injury. A regional study of Canadian adolescents found that approximately 20% of all adolescents have sustained a concussion[11]

Chronic Traumatic Encephalopathy (CTE)

Chronic traumatic encephalopathy (CTE) is a term used to describe brain degeneration likely caused by repeated head trauma. CTE is thought to significantly increase the risk for dementia.[12] A diagnosis of CTE can only be made during autopsy. CTE is a rare condition and usually found in individuals who play contact sports.

Symptoms and Severity

Symptoms

The cognitive presentation and symptoms after a TBI can be variable. Difficulties in the domains of complex attention, executive ability, learning, and memory are common as well as slowing in speed of information processing and disturbances in social cognition. In more severe TBIs that involve brain contusion, hemorrhage, or a penetrating injury, there can be more neurocognitive deficits, such as aphasia, neglect, and constructional dyspraxia. TBIs are also associated with:

  1. Affective changes (irritability, easy frustration, tension and anxiety, affective lability)
  2. Personality changes (disinhibition, apathy, suspiciousness, aggression)
  3. Physical changes (headache, fatigue, sleep disorders, vertigo or dizziness, tinnitus, hyperacusis, photosensitivity, anosmia, reduced tolerance to psychotropic medications)
  4. Loss of smell can often occur due to sinonasal tract disruption, direct shearing or stretching of olfactory nerve fibers at the cribiform plate, or local contusion or bleeding within the olfactory bulb and cortex.[13]
  5. Seizures, hemiparesis, visual disturbances, cranial nerve deficits (particularly in more severe TBI, neurological symptoms and signs)
Severity

Severity ratings for traumatic brain injury

Injury characteristic Mild TBI Moderate TBI Severe TBI
Loss of consciousness <30 minutes 30 minutes-24 hours >24 hours
Posttraumatic amnesia <24 hours 24 hours-7 days 7 days
Glasgow Coma Scale on assessment 13-15 (not below 13 at 30 minutes) 9-12 3-8

In the First Few Months After a TBI...

It's important to look out for:
  • Depression
  • Cognitive and memory impairment
  • Sleep changes and sleep disorders
  • Behavioural changes according to family and collateral report

Pathophysiology

Depending on the neuroanatomical region of the injury, symptoms of TBI can vary as described above. In general, TBIs can cause a variety of cytotoxic processes, including axonal injury, free-radical injuries, changes in Mg+2 and Ca+2 signalling, and neurotransmitter excitotoxicity. These changes contribute to a range of cognitive and neuropsychiatric symptoms.

Differential Diagnosis

In some instances, the severity of neurocognitive symptoms may appear to be inconsistent with the severity of the TBI. After previously undetected neurological complications (e.g., chronic hematoma) are excluded, the possibility of diagnoses such as somatic symptom disorder or factitious disorder need to be considered. Posttraumatic stress disorder can co-occur with the neurocognitive impairment and have overlapping symptoms (e.g. - difficulty concentrating, depressed mood, aggressive behavioural disinhibition).

Investigations

Biomarkers for acute concussion have been identified, including ubiquitin carboxy-terminal hydrolase L1 (UCH-L1).[14] The FDA has recently approved this for clinical use.

Treatment

There are no approved pharmacological treatments for TBI, and use is off-label to address neuropsychiatric symptoms related to the injury.[15] A variety of medications can be used depending on the symptom.

If there is no urgent or acute symptoms, do watchful waiting and assess for spontaneous resolution of symptoms first. A “start low and go slow” approach is important as those with TBI have increased sensitivity to to cognitive side effects of psychotropic and neurological medications.

TBI-related Cognitive Deficits

Dopamine agonists Amantadine 100 to 300mg daily, bromocriptine 5 to 45mg daily
Acetylcholinesterase inhibitors Donepezil, rivastigmine 3 to 6mg daily[16]
Stimulants Methylphenidate 10 to 15mg BID, modafinil 100 to 400mg daily
*Off-label

Depression

SSRIs Fluoxetine 60mg daily, sertraline 100mg daily
*Off-label

Aggression/Agitation

Anticonvulsants Valproic acid 600 to 2250mg daily, carbamazepine 400 to 800mg daily
Beta-blockers Propranolol up to 420mg/daily,[17] pindolol 60 to 100mg daily
Mood stabilizers Lithium 900mg daily
Second generation antipsychotics Clozapine 300 to 500mg daily, quetiapine 25 to 300mg daily, ziprasidone 20 to 80mg daily
*Off-label

Somnolence

Stimulants Methylphenidate 10 to 15mg BID, modafinil 100 to 400mg daily
*Off-label

Guidelines

Traumatic Brain Injury (TBI) Guidelines

Guideline Location Year PDF Website
Evidence-Based Review of Moderate-to-Severe Brain Injury (ERABI) Canada 2007 Link Link
Ontario Neurotrauma Foundation Canada 2017 Link Link
British Columbia Medical Journal (BCMJ) Canada 2010 - Link
BMJ Open (Systematic Review) UK 2019 - Link
PsychiatricTimes (Expert Opinion) USA 2019 - Link
Tele-Rehabilitation Interventions through University-based Medicine for Prevention and Health (TRIUMPH) USA 2020 Link -

Resources

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Articles

References

1) Wortzel, H. S., & Arciniegas, D. B. (2014). The DSM-5 approach to the evaluation of traumatic brain injury and its neuropsychiatric sequelae. NeuroRehabilitation, 34(4), 613-623.
2) Lauterbach, M. D., Notarangelo, P. L., Nichols, S. J., Lane, K. S., & Koliatsos, V. E. (2015). Diagnostic and treatment challenges in traumatic brain injury patients with severe neuropsychiatric symptoms: Insights into psychiatric practice. Neuropsychiatric disease and treatment, 11, 1601.
3) Lauterbach, M. D., Notarangelo, P. L., Nichols, S. J., Lane, K. S., & Koliatsos, V. E. (2015). Diagnostic and treatment challenges in traumatic brain injury patients with severe neuropsychiatric symptoms: Insights into psychiatric practice. Neuropsychiatric disease and treatment, 11, 1601.
4) Laskowski RA, Creed JA, Raghupathi R. Pathophysiology of Mild TBI: Implications for Altered Signaling Pathways
5) Thompson, H. J., McCormick, W. C., & Kagan, S. H. (2006). Traumatic brain injury in older adults: epidemiology, outcomes, and future implications. Journal of the American Geriatrics Society, 54(10), 1590-1595.
6) Thompson, H. J., McCormick, W. C., & Kagan, S. H. (2006). Traumatic brain injury in older adults: epidemiology, outcomes, and future implications. Journal of the American Geriatrics Society, 54(10), 1590-1595.
7) Rapoport, M. J., & Feinstein, A. (2000). Outcome following traumatic brain injury in the elderly: a critical review. Brain injury, 14(8), 749-761.
8) Rapoport, M. J., McCullagh, S., Streiner, D., & Feinstein, A. (2003). Age and major depression after mild traumatic brain injury. The American Journal of Geriatric Psychiatry, 11(3), 365-369.
9) Ponsford, J., Alway, Y., & Gould, K. R. (2018). Epidemiology and natural history of psychiatric disorders after TBI. The Journal of neuropsychiatry and clinical neurosciences, 30(4), 262-270.
10) Tanev, K. S., Pentel, K. Z., Kredlow, M. A., & Charney, M. E. (2014). PTSD and TBI co-morbidity: scope, clinical presentation and treatment options. Brain injury, 28(3), 261-270.
11) Veliz, P., McCabe, S. E., Eckner, J. T., & Schulenberg, J. E. (2017). Prevalence of Concussion Among US Adolescents and Correlated Factors. Jama, 318(12), 1180-1182.
12) Schneider, J. A. (2019). Multiple pathologic pathways to dementia in football players with chronic traumatic encephalopathy. JAMA neurology, 76(11), 1283-1284.
13) Howell, J., Costanzo, R. M., & Reiter, E. R. (2018). Head trauma and olfactory function. World journal of otorhinolaryngology-head and neck surgery, 4(1), 39-45.
14) Mondello, S., Palmio, J., Streeter, J., Hayes, R. L., Peltola, J., & Jeromin, A. (2012). Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is increased in cerebrospinal fluid and plasma of patients after epileptic seizure. BMC neurology, 12(1), 85.
15) Yue, J. K., Burke, J. F., Upadhyayula, P. S., Winkler, E. A., Deng, H., Robinson, C. K., ... & Ngwenya, L. B. (2017). Selective serotonin reuptake inhibitors for treating neurocognitive and neuropsychiatric disorders following traumatic brain injury: an evaluation of current evidence. Brain sciences, 7(8), 93.
16) Silver, J. M., Koumaras, B., Chen, M., Mirski, D., Potkin, S. G., Reyes, P., ... & Gunay, I. (2006). Effects of rivastigmine on cognitive function in patients with traumatic brain injury. Neurology, 67(5), 748-755.
17) Fleminger, S., Greenwood, R. R., & Oliver, D. L. (2003). Pharmacological management for agitation and aggression in people with acquired brain injury. Cochrane Database of Systematic Reviews, (1).