A 26-year-old man is brought to the emergency department after a high-speed motorcycle collision. The patient was thrown several feet after his motorcycle collided with a car. On arrival, he is profoundly comatose. A CT scan of the head performed within an hour of the event shows no abnormalities. The patient dies several hours later, and autopsy examination is performed. Brain histopathology shows widespread axonal swelling, predominantly at the gray-white junction. Immunohistochemical staining of these axons reveals accumulation of alpha-synuclein and amyloid precursor proteins. Which of the following is the most likely cause of these observed findings?

Question

A 26-year-old man is brought to the emergency department after a high-speed motorcycle collision.  The patient was thrown several feet after his motorcycle collided with a car.  On arrival, he is profoundly comatose.  A CT scan of the head performed within an hour of the event shows no abnormalities.  The patient dies several hours later, and autopsy examination is performed.  Brain histopathology shows widespread axonal swelling, predominantly at the gray-white junction.  Immunohistochemical staining of these axons reveals accumulation of alpha-synuclein and amyloid precursor proteins.  Which of the following is the most likely cause of these observed findings?

Quizplus · Accepted Answer

11ec160b_39e2_d102_9249_9172e2640bdd_MD0001_00 This patient has histopathologic findings of diffuse axonal injury (DAI), a type of severe traumatic brain injury that can occur from direct blunt force injury (eg, head hitting windshield) or abrupt changes in acceleration-deceleration (eg, restrained passenger coming to sudden stop after a collision). Transfer of force can result in immediate shearing of the white matter tracts or induce secondary biochemical changes leading to degradation of the axonal cytoskeleton with subsequent axon breakage. Normal axonal transport is inhibited, leading to accumulation of axonally transported proteins (eg, amyloid precursor, alpha-synuclein) within axonal swellings at the point of injury (eg, axonal bulb formation). Presentation varies based on the extent of injury; most patients are comatose (Glasgow Coma Score <8); however, those with very mild DAI may have only concussive symptoms (eg, headache, amnesia). CT scan has low sensitivity for diagnosis and is often normal, but MRI may demonstrate lesions at the gray-white junction. Microscopically, DAI is visible as widespread axonal swelling, most pronounced at the gray-white matter junction. Prognosis is poor, with up to 25% of cases resulting in death. (Choices A and C) Diffuse cerebral hypoperfusion typically occurs in the setting of systemic hypotension or cardiac arrest. Watershed zone infarctions or diffuse edema with blurring of the gray-white junction are often visible on imaging. Ischemic neurons can release glutamate, leading to overactivation of the NMDA receptor with continuous membrane depolarization. This results in neuronal damage in a process known as excitotoxicity. Red neurons with intensely eosinophilic cytoplasm are seen on histopathology. (Choice B) Disruption of the bridging cortical veins results in subdural hematoma; the elderly are at increased risk due to cerebral atrophy (stretching of the bridging veins increases the risk of tear). Subdural hematomas are visible on imaging as crescent-shaped hyperdensities that cross suture lines. (Choice E) Subarachnoid hemorrhages are typically caused by rupture of saccular aneurysms but may be associated with trauma (typically with associated brain contusions); head CT scan demonstrates blood within the subarachnoid space. Educational objective: Diffuse axonal injury (DAI) is a type of traumatic brain injury that results from disruption of the white matter tracts. Microscopically, DAI is visible as widespread axonal swelling, most pronounced at the gray-white matter junction, with accumulation of transport proteins (eg, amyloid precursor, alpha-synuclein) at the site of injury. __________ References: Axonal pathology in traumatic brain injury. (http://www.ncbi.nlm.nih.gov/pubmed/22285252)

A 26-Year-Old Man Is Brought to the Emergency Department After