Simplest way to understand Traumatic brain Injury and its Neuropsychiatric complications

1. Neuropsychiatric Consequences
of Traumatic Brain Injury
Dr. Dikshya Upreti
PG Resident
Department of Psychiatry
NMCTH, Birgunj, Nepal

2. Introduction
• Traumatic Brain Injury (TBI) refers to external mechanical force
acting on the brain which cause temporary or permanent dysfunction.
• The neuropsychiatric consequences of TBI encompass disorders also
seen in patients without brain injury and those unique to patients with
brain damage.

3. Hill et al., 2016

5. Epidemiology
• 80 percent of patients with TBI have mild head injury
• 10% have moderate head injury
• Remaining 10% severe head injury
• TBIs is common among adolescents and young adults, with a second peak
in elderly individuals.
• Males(40%) > Female
• Low socioeconomic status also experience higher rates of TBI than other
groups.
• Among younger adults, motor vehicle accidents and assaults produce the
most TBIs.
KAPLAN and SADOCK’S Comprehensive Textbook of Psychiatry 10th Edition

6. PATHOLOGY
TBI pathogenesis is a complex process that results from two injuries:
1. Primary injuries
2. Secondary injuries
These injuries lead to temporary or permanent neurological deficits.
• The primary deficit is direct external impact
of the brain.
• The secondary injury can happen from
minutes to days from the primary impact.

7. PATHOLOGY
• Secondary injury consists of a molecular, chemical, and inflammatory
cascade responsible for further cerebral damage
• After the second injury phase follows the recovery period, which consists of
reorganization in an anatomical, molecular, and functional level.

8. Primary brain damage
Primary brain damage results from:
1. Contact forces
2. Inertial forces that occur at the time of injury
• Contact forces may result in laceration to the scalp, skull fractures,
intracranial hemorrhages, contusions, and intracerebral hemorrhages.
• Inertial loading consists of acceleration/deceleration and rotational
forces that result in diffuse axonal injury and eventually acute subdural
hematoma from the tearing of subdural bridging veins.

9. Secondary brain damage
• Secondary brain damage is produced by pathological processes that
are initiated at the moment of injury but span a variable period
following the traumatic episode.
These include :
• Brain damage secondary to ischemia (e.g., that resulting from
associated hypotension and/or hypoxia)
• Brain swelling
• Raised intracranial pressure (with consequent reduction of cerebral
perfusion pressure)
• Infection

10. Neurobiological Changes
• TBI demonstrate cell death in the hippocampus and other medial
temporal lobe structures that occur through both necrotic and apoptotic
cascades.
• Diffuse neuronal damage and cell loss may progress over weeks to
months
• The initial insult is selectively in vulnerable regions of the prefrontal
cortex, hippocampus, thalamus, striatum, amygdala, and forebrain
nuclei.

11. Measuring head injury severity
Clinical methods: (Indicators of head injury severity)
1. Glasgow Coma Scale
2. Duration of loss of consciousness/coma
3. Evidence of behavioral/cognitive change in the immediate aftermath
suggestive of delirium
4. Neurological symptoms and signs
5. Evidence of skull fracture and/or other abnormalities on neuroimaging
6. Blood in the CSF
7. Duration of PTA: Interval between the injury and return of normal day-to-
day memories

13. Measuring head injury severity
Less useful indicators
1. Duration of retrograde amnesia: the period leading up to the injury
for which memories have been lost
2. Abnormalities on EEG
3. Markers of cell damage (e.g. S-100B)
4. Evidence of injury to head, e.g. lacerations, bruising, bleeding from
ears, fracture of maxilla/zygoma
Lishman’s Organic Psychiatry, 4th edition

14. Classification of severity of traumatic brain
injury
Mild Moderate Severe Very severe
GCS 13–15 9–12 6–8 3–5
LoC ≤30 min >30 min to 6 hours >6 hours to 7 days >7 days
PTA ≤24
hours
>24 hours to 14
days
>14 days to 8
weeks
>8 weeks
Lishman’s Organic Psychiatry, 4th edition

15. Likely outcome for given duration of PTA
PTA duration Likely outcome
<1 hour Usually return to work within 1 month
<1 day Usually return to work within 2 months
<1 week Usually return to work within 4 months
>1 week Often followed by invalidism extending over the greater part of a year
>2 week Almost inevitable measurable residual cognitive problems, of variable
impact
>1 month At best a reduced work capacity, at work some community
supervision
>3 months Makes voluntary or subsidized work a likely best outcome, while at
worst residential placement may be needed
Lishman’s Organic Psychiatry, 4th edition

16. Laboratory tests
Serum markers for TBI include:
Serum S-100B (90 percent sensitivity)
Ideally, serum markers could objectively diagnose TBI in symptomatic
patients with normal neuroimaging findings.
Neuronal proteins Glial proteins
Neuron-specific enolase S100B
Cleaved tau protein glial fibrillary acidic protein
Neurofilament
Ubiquitin C-Terminal
hydroxylase-l1
KAPLAN and SADOCK’S Comprehensive Textbook of Psychiatry 10th Edition

17. Neuroendocrine dysfunction may accompany
head injury
• Growth hormone deficiency (GHD) in adults:10 to 30 percent, most common
endocrinopathy
• Others rates of LH, FSH, ACTH, TSH, prolactin, and ADH abnormalities range
from 2 to 17 percent.
• About 3 to 5 percent of patients with TBI may show multiple neuroendocrine
abnormalities.
• Pituitary hormone deficiencies, as the pituitary’s location makes it vulnerable to
injury in TBI.
• Antidiuretic hormone (ADH) deficiency causes diabetes insipidus manifests
clearly in the acute stage.
KAPLAN and SADOCK’S Comprehensive Textbook of Psychiatry 10th Edition

18. Electrophysiological Studies
• Conventional EEG recordings are currently used in trauma intensive care
units for monitoring procedures and for brain death diagnosis.
• EEG is also invaluable in the diagnosis of status epilepticus and is the
primary diagnostic procedure to localize a post-traumatic epileptic focus.
• Quantitative EEG (Q-EEG) is currently used as an adjunctive diagnostic
technique in the evaluation of slow-wave abnormalities associated with
brain injuries and in the diagnosis of post-traumatic temporal lobe epilepsy.

19. Neuroimaging
• CT and MRI are routinely used for the evaluation of patients with TBI.
• CT remains the most efficient for hematomas and is the study of choice for
evaluating patients with rapid changes in their neurological status.
• MRI, however, shows more sensitivity in detecting the more prevalent
posttraumatic non hemorrhagic lesions (e.g., cortical contusions and deep
white matter lesions) and in identifying small subdural collections.
• Further research is going for other advanced imaging methods such as
single photon emission tomography, and positron emission tomography.

20. (A) Pre-injury magnetic resonance image (MRI) approximately 2 years prior to TBI where the normal size of the
ventricular system and ventricle-to-brain (VBR) ratio of 1.64 (normal is approximately 1.5 with a 0.5 standard
deviation).
(B) Day-of-injury initial CT demonstrating brain edema and reduced VBR, which continues to be reflected in (C,D).
(E) Distinct neurodegeneration has occurred by 16 weeks post-injury, reflected as ventricular dilation and increased
VBR, with continued neurodegeneration out to 2 years post-injury as seen in (F).
Erin D. Bigler, 201

21. Consequences of TBI
• Approximately 7 percent of patients hospitalized for TBI will die from
their injuries
• Individuals who survive a TBI face an elevated risk of subsequent
stroke and increased all-cause mortality.
• Neuropsychiatric disorders are probably the most frequent
complication of TBIs

22. CLINICAL FEATURES
Acute Behavioral Consequences of Traumatic Brain Injury
1. Loss of consciousness
2. Post traumatic confusion/delirium
3. Post traumatic amnesia (PTA)

23. DSM-5 Classification of Some Behavioral Syndromes
(Occurring after traumatic brain injury)
1. Delirium due to traumatic brain injury
2. Major and minor neurocognitive disorder due to traumatic brain
injury
3. Depressive disorder due to traumatic brain injury
With depressive features
With major-depressive-like episode
With mixed features

24. DSM-5 Classification of Some Behavioral Syndromes
(Occurring after traumatic brain injury)
4.Bipolar and related disorder due to traumatic brain injury
With manic features
With manic- or hypomanic-like episode
With mixed features
5.Anxiety disorder due to traumatic brain injury
Post-traumatic stress disorder
6. Psychotic disorder due to traumatic brain injury

25. Cognitive Disorders
Two categories:
1. Those which begin at the time of injury
2. Those which develop years to decades later

26. The DSM-5 defines major neurocognitive
disorder due to TBI
1. Significant decline in at least one cognitive domain, interfering with
everyday activities, and not occurring solely in the context of
delirium
2. A history of head trauma accompanied by loss of consciousness,
PTA, disorientation and confusion, and/or neurological changes
3. Symptoms beginning at the time of the injury and continuing after
the acute post-injury phase.
Mild neurocognitive disorder due to TBI follows the same criteria,
except that the decline in cognitive domain(s) is modest and does not
interfere with everyday life.

27. Personality Changes
• A change from the individual’s previous personality profile (or a
deviation of normal development in children) and is attributable to the
pathophysiological changes triggered by brain trauma.
• Irritable, childish, inconsiderate, capricious, anxious, or aggressive,
apathetic, withdrawn
• They lack foresight and misjudge the consequences of their actions.
• Disinhibition is a frequent and striking clinical feature that may lead to
antisocial behavior.

28. Depressive Disorders
• Using the DSM-5 diagnostic criteria:
Depressive disorders associated with TBI are categorized as
“Depressive Disorder due to Traumatic Brain Injury”.
• 6 to 77% depressive disorders following TBI
• More frequent in patients who suffered TBIs than in patient who
underwent similar levels of stress (e.g., motor vehicle accidents) but
who did not sustain brain injury

29. • The differential diagnosis of post-TBI major depression includes
adjustment disorder with depressed mood, apathetic syndromes, and
PBA.
• Patients with adjustment disorders develop short-lived and relatively
mild emotional disturbances within 3 months of a stressful life event,
and symptoms do not persist longer than 6 months after the stressful
event or its consequences cease

30. Pseudobulbar Affect
• PBA manifests as sudden and uncontrollable affective outbursts (e.g.,
crying or laughing), which may be congruent or incongruent with the
patient’s mood, and can occur spontaneously or may be triggered by
minor stimuli.

31. Apathy
• Apathy occurs frequently with TBI
• Estimated prevalence ranging from 1/5 to almost ¾ of patients with
TBI.
• Apathy consists of impairment of motivation, initiation, interest,
activity, emotional responsiveness, and/or spontaneity.
• Apathy differs from depression in that it is not associated with sadness
or low mood.

32. Trauma- and Stressor-Related Disorders
• PTSD, the prototypical trauma-related disorder, is characterized by
recurrent intrusive recollections, distressing dreams, and flashbacks of
the traumatic event.
• Patients with PTSD show features of increased arousal such as
difficulty falling or staying asleep, exaggerated startle response, and
irritability.
• Individuals who sustain a TBI are more likely to develop PTSD than
those who suffer other types of traumatic injuries

33. Anxiety Disorders
• Prevalence of generalized anxiety disorder (GAD) after TBI varies from 2
to 32 percent
• The most common post TBI anxiety disorder.
• Rates of panic disorder following TBI range from 6 to 14 percent
• Post-TBI-specific phobias show rates of 1 to 10 percent
• Social anxiety disorder
KAPLAN and SADOCK’S Comprehensive Textbook of
Psychiatry 10th Edition

34. Substance-Related and Addictive Disorders
• TBI increases the risk of binge drinking and the likelihood of being
diagnosed with an addiction-related disorder
• The combined effects of traumatic injury and the toxicity of chronic
substance abuse (particularly alcohol) might produce greater
disruption of the neural circuits involved in mood regulation,
motivation, and reward processing

35. Psychotic Disorders
• Following DSM-5 criteria, psychotic disorder due to TBI consists of
prominent hallucination or delusions occurring as a direct
physiological consequence of the TBI.
• Delusional content including Capgras syndrome, reduplicative
paramnesia, delusional jealousy, Cotard syndrome, somatic delusions,
and Fregoli syndrome

36. Potential Characteristics Discriminating Between
PD-TBI and Schizophrenia
PD-TBI Schizophrenia
Presence of Negative
Symptoms
37% 50%–90%
MRI/CT: Positive Findings 70% 12%–35%
Atrophy Not seen Seen
Focal abnormalities Common 6%–9%
Most common finding 74% frontal
47% temporal
Enlarged ventricles
Whole brain, Hippocampal
atrophy, enlarged ventricles
EEG: Positive Findings 70% 20%–60%
Most common finding Temporal slowing Frontal slowing
Daryl Fujii Et al, 2005

37. Treatment of depression in TBI
• Low anticholinergic activity, minimal lowering of seizure threshold,
and low sedative effects are the most important factors to be
considered in the choice of an antidepressant drug.
Ref: KAPLAN and SADOCK’S Comprehensive Textbook of Psychiatry 10th Edition
• SSRIs represent a good first-line choice for pharmacotherapy and are
safe and well-tolerated in individuals with TBI
JR. Fann Et al, 2009
KAPLAN and SADOCK’S Comprehensive Textbook of Psychiatry 10th Edition

38. Treatment of depression in TBI
• TCAs in TBI are mixed
• Methylphenidate is effective for treating depression in TBI, and may
also improve fatigue and cognitive functioning
• Bupropion, while not absolutely contraindicated in TBI, can lower the
seizure threshold; using the lowest effective dose, the sustained-release
formulation, and careful monitoring may help reduce the risk.
KAPLAN and SADOCK’S Comprehensive Textbook of
Psychiatry 10th Edition

39. • ECT is not contraindicated in patients with TBI and may be considered
if other methods of treatment prove to be unsuccessful, though there
are no systematic studies of its effects.
• Cognitive behavioral therapy (CBT) may improve mood in patients
with TBI, either alone or as part of a neurorehabilitation program
• Supportive psychotherapy equally improved depression following
TBI.

40. Treatment in PBA
• Treatment options for PBA in TBI remain understudied
• SSRIs represent a reasonable first-line strategy.
• However, Combination therapy with dextromethorphan and quinidine
can help treat PBA, but has not been specifically studied in TBI.

41. Treatment of psychosis
• Till date, no clinical trials have examined the pharmacotherapy of
psychosis due to TBI.
• By extrapolation from the treatment of idiopathic psychosis,
antipsychotic medications will likely represent the mainstay of
treatment
• However, given the possible association between post-traumatic
psychosis and epilepsy, AEDs may also represent an option.

42. COURSE AND PROGNOSIS
• Assessing the course and prognosis of patients with TBI involves the
longitudinal analysis of neurological, neuropsychological, psychiatric,
and psychosocial variables.
• The long-term outcome of patients with TBI primarily relates to the
severity of brain injury, type and location of intracranial lesion, age,
and efficacy of acute medical and surgical treatment.

43. References
• KAPLAN and SADOCK’S Comprehensive Textbook of Psychiatry
10th Edition
• Lishman’s Organic Psychiatry, 4th edition
• Different article

44. Thank you