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