1. Neuropathology for neurologist conference Case presentation
Wilson Heredia, PGY 3
September 12th 2016

2. HPI
J.A. is a 23 year old male with no significant past medical history who was brought by EMS after he was found at the scene of a MVA, involving the car where he was a back seat passenger and a light post. He was not wearing his seat belt.
As per the EMS Report he was conscious, but disoriented and could not recall the details of the accident.
Analysis of the crash scene revealed that he hit his head with the rear door window.

3. ED Course
At time of arrival patient was conscious but drowsy, able to speak and answer questions.
Vitals were WNL.
He still could not remember the details of the accident, but could recall the ambulance ride to the Hospital.

4. Histories PMhx – No significant health conditions
PSxHx – Denies Surgeries
Allergies – NKDFA
FMHx – ?
Social – Recently graduated from college, denies drug use, social alcohol use.
Meds – Multivitamins

5. Physical Exam
General: Awake, but drowsy, and at time of exam becoming less responsive
Skin: redness and swelling over the right side of the scalp
CN: Grossly intact, except for decrease vision acuity on the right eye
Motor: Normal bulk and tone. No tremor or involuntary movements.
Deltoid Biceps Triceps Wr ext Wr flex Handgrip
Left / / / / / /5
Right / / / / / /5
Iliopsoas Knee flex Knee ext Tib Ant Gastroc
Left / / / / /5
Right / / / / /5
Reflexes: 2+ and symmetric in biceps, triceps, brachioradialis, patellar and achilles tendons. Plantar responses flexor. No pathological reflexes.
AT THIS POINT PATIENT BECAME UNRESPONSIVE!!!! -> EMERGENT INTUBATION.
Great
You might want to enter a discussion of
Subdural versus epidural versus DAI and what if anything would distinguish them

6. Riddle me this?
What are you thinking at this point??
DDs?

7. Imaging – CT Scan

8. Riddle me that??
DDs?

9. Imaging – MRI

10. Repeat MRI

11. Diffused traumatic brain/Axonal injury (DAI)
Pattern of injury throughout the brain caused by widespread traumatic disruption of its nerve cells, identified microscopically as axonal disruptions.
Most commonly with motor vehicle accidents or any other mechanism of injury in which the head is subjected to a large amount of force, causing rotational stretching/twisting of the brain tissue within the confines of the skull.
The head is usually in motion and the injury is caused by rapid and severe deceleration of the head as it impacts against another object such as a windshield.
There is often additional evidence of severe head injury, such as skull fractures, subdural blood, subarachnoid blood, and cortical contusions, but such additional injuries are not necessary for the diagnosis.

12. Mechanism
Direct impact of moving head with non-moving object -> acceleration – deceleration event.
Grey matter is less dense than white matter, as the brain rotates during acceleration-deceleration events, lower density tissues move more rapidly than those of greater density ->
This velocity difference causes shearing of neuronal axons which traverse the junction of gray and white matter -> Lesions are seen most frequently in the areas of the brain where white and gray matter meet.
Several directions of stretching/straining can be observed.

13. Mechanism cont.
The magnitude of axonal injury in DIA is dependent on 3 factors: 1) the distance from the center of rotation, 2) the arc of the rotation, and 3) the duration and intensity of the force.
Typically, the process is widespread and bilateral, most frequently involving the frontal and temporal lobe white matter, corpus callosum, and areas of the brainstem not involved with basic life functions.
There is almost no correlation between DAI and the presence or absence of skull fractures, or subarachnoid or subdural bleeding

14. Phases of injury
Primary injury, in which axons undergoing shear forces are stretched at the moment of impact (no rupture).
Secondary, or delayed phase, where stretched axons undergo swelling and rupture as a result of biochemical changes related to the primary injury -> Initial abnormal changes in stretched axons, known as “bulb” formation, is generally seen within a day or two of injury, but completion of the degenerative process may take up to 2 years.
It may take up to 2 years to fully develop clinical symptoms in individuals who are not rendered unconscious at the time of initial injury.
While mechanical separation of neuronal axons may occur at the moment of injury, it is now widely held that the greatest injury to neurons with DAI occurs as a result of primary strain (not rupture), followed by delayed secondary rupture due to metabolic disturbances within the neuronal axon, rather than tearing of axons at injury.  

15. Classification
The Adams classification categorizes DAI based on the  degree and location of injury-related lesions in the white matter:
Mild (grade 1) is characterized by microscopic changes in the white matter of the cerebral cortex, corpus callosum, brainstem, and occasionally the cerebellum.
Moderate (grade 2) is defined by grossly evident focal lesions isolated to the corpus callosum.
Severe DAI (grade 3), there are additional focal lesions in the dorsolateral quadrants of the rostral brainstem (commonly in the superior cerebellar peduncle). - > Severe DAI results in an immediate loss of consciousness, and most individuals with a severe DAI injury (>90%) remain in a persistent vegetative state. The prognosis worsens in direct relationship to the number of lesions present. GCS score of 8 or less immediately after injury have a poor prognosis for complete recovery.

16. Gross inspection of DAI
May have hemorrhages of the corpus callosum and superior cerebellar peduncle region.
May have hemorrhages of the deep nuclei.
May have gliding contusions in the parasagittal white matter.
May have small hemorrhages scattered throughout the cerebral hemispheric white matter and brain stem.

17. Histopathology of DAI
Widespread dystrophic axons visible on routine H-E stained sections after approximately 1 day's survival time and with β-amyloid precursor protein immunohistochemistry (BAPP) after approximately 2 hours’ survival time.
Injured axons undergo physiologic changes over time, becoming gradually more swollen and varicose before disconnecting.
It’s a must to distinguish diffuse traumatic axonal injury from vascular axonal injury or other causes of axonal injury.

18. H-E Stain microscopy

19. BAPP Stain Microscopy

20. DAI Histopathology
Mild
H&E
APP
IBA1
CD68
Moderate NF CC
Severe

21. Management ICU/Supportive care.
Currently there are no known specific drug therapies to inhibit or reverse the process of nerve axon dysfunction in Diffuse Axonal Injury.
Drug therapy at this time is restricted to treating the neuropsychiatric and neurobehavioral conditions that may occur as a result of injury. Depression, anxiety, agitation, and impulsive behavior may respond to specific pharmacologic agents, but great care must be taken in the administration of such medications to DAI patients.  
Symptoms may be aggravated rather than reduced, and because the symptoms of Diffuse Axonal Injury often change over time (especially during the first few years after injury), long-term pyschotropic drug regimens without frequent reassessment and follow up are to be avoided.

22. Prognosis
90% of individuals with severe DAI remain in a persistent vegetative state indefinitely, and may remain so for decades.
Of the 10% who regain consciousness, the majority will sustain permanent and far- reaching functional deficits.
Only a small percentage of these individuals will attain near-normal neurological function. What improvement occurs usually does so within the first months after the injury.
a patient suffering head injury with DAI has a GCS of 8 or less in the immediate post-injury period, the chances of permanent and severe neurological dysfunction are very likely.
“As a rule, if PTA lasts less than 1 week, a reasonably good outcome is expected. If PTA lasts longer than 1 month, significant disability is likely; a good proportion of those affected will not be able to return to work or to independent living. In general, younger individuals (those in their late teens or 20s) tend to do much better.
The outlook for those with mild or moderate Diffuse Axonal Injury is better, especially for teens and individuals in their 20s.