THE FORENSIC NEUROPATHOLOGY OF
BLUNT FORCE TRAUMA OF THE BRAIN
Part 5: Diffuse Traumatic Brain Injury
Bennet I. Omalu, M.D., M.P.H.Forensic Pathologist/ Neuropathologist
DIFFUSE TRAUMATIC BRAIN INJURY
• The sine qua non of Diffuse Traumatic Brain Injury is Diffuse Traumatic Axonal Injury
• Typically associated with diffuse inertial biomechanical loading and acceleration-deceleration shearing forces
Axonal injury is not localized to a single region of the brain, it is diffusely spread
• Para-sagittal structures of the brain are most vulnerable especially the splenium of the corpus callosum
• Diffuse Traumatic Axonal Injury is associated with gliding contusions
• Note that axonal injury may be associated with non-traumatic causes like viral encephalitis, hypoxic injury and toxic encephalopathies, traumatic axonal injury is solely caused by trauma
DIFFUSE TRAUMATIC BRAIN INJURY
• There are three neuropathologic grades of diffuse traumatic axonal injury:
• Adams Grade 1 DAI
Diffuse cytotoxic edema, + APP immunohistochemistry
• Adams Grade 2 DAI
Diffuse cytotoxic edema, petechial/ecchymotic hemorrhages in corpus callosum, + APP
• Adams Grade 3 DAI
Diffuse cytotoxic edema, petechial/ ecchymotic hemorrhages in corpus callosum and dorso-lateral brainstem, + APP. Typically associated with loss of consciousness at the scene
PATHOLOGIC DIAGNOSIS OF DIFFUSE AXONAL INJURY
• Following gross grading of DAI, tissue immuno-histochemistry must be performed using antibodies for Amyloid Precursor Protein [APP]
• Amyloid Precursor Protein [APP]
A single-membrane spanning protein found in cell membranes and membranous organelles of every cell
Involved in diverse metabolic and regulatory cell pathways including cell adhesion and inter-cellular signaling
Encoded by APP gene on Chromosome 21
Parent compound of Beta-Amyloid peptide of Alzheimer’s Disease
Synthesized in the perikaryon
Fast antero-grade and retro-grade axonal transport by microtubules [100-400 mm/day]
Without axonal injury APP is not detected by tissue immunohistochemistery
PATHOLOGIC DIAGNOSIS OF DIFFUSE AXONAL INJURY
• Amyloid Precursor Protein [APP], cont’d
Following axonal injury and disruption of the micro-tubule cytoskeleton, APP accumulates both proximally and distally to point of axonal injury
It takes APP 2 – 3 hours post injury to accumulate sufficiently to be detected
This can shorten to 1 hour with antigen retrieval methods
APP has been observed up to 99 days post injury [3 months]
APP associated with diffuse hypoxic-ischemic injury shows a geographic pattern of immunopositivity
Trauma-induced DAI exhibits a diffuse focal pattern of APP+
Using silver impregnation and H&E stains, axonal injury can be identified after 15 hours of injury, axonal spheroids of Cajal, axonal viscosities and swellings may be seen
APP immuno-histochemistry is an important tool in medico-legal cases
DAI AND APPDAI AND APP
Adams Grade 2 DAI with corpus callosal hemorrhages and a small gliding contusion [*]
*
DAI AND APPDAI AND APP
Axonal Spheroids and Varicosities
APP IMMUNOSTAIN
H&E
OTHER TYPES OF DIFFUSE BRAIN INJURY
• DIFFUSE VASCULAR INJURY
Presents immediately after trauma, usually fatal
Brain exhibits only peri-vascular petechial and micro-hemorrhages in lobar cortical white matter
• DIFFUSE CEREBRAL FAT EMBOLISM
Associated with fractures of long bones with surgical fixation/manipulation
Associated with extensive soft tissue and crush injuries
Presents 2 to 3 days after trauma
Manifests as diffuse cortical white matter petechial perivascular hemorrhages
Fat stains show intra-luminal fat globules in penetrating parenchymal vessels
Peri-vascular rarefaction and demyelination may follow