A young man sustained a serious head injury in a car accident, but routine brain CT and MRI scans are normal. Your next step?
Figure 1. Axial MRI gradient echo demonstrates multiple small acute hemorrhages in the temporal lobe and two foci of hemorrhage in the cerebellum.
Figure 2. Axial MRI gradient echo reveals two small foci of acute hemorrhage in the right frontal lobe, one in the left frontal lobe, as well as a left scalp hematoma.
A 21-year-old man* was ejected from a speeding motor vehicle after it slammed into a tree. Emergency medical services personnel found him unconscious with stable vital signs. On examination in the emergency department, he became agitated and required intubation, sedation, and transfer to the intensive care unit. His girlfriend, who was not in the car, arrived later and provided his history.
Past medical and psychiatric history is negative; family history is unremarkable. The patient takes no medications and has no allergies. He does not smoke or abuse alcohol; however, he uses marijuana regularly. He is single and works as a chef at a local restaurant. When the accident occurred, he had been on his way to celebrate his birthday.
The next day, the patient wakes up and is extubated. He complains of pain in his right arm and left leg, a severe headache, and blurry vision.
Physical and neurological examination
He has a large scalp hematoma and swelling of the right arm and left leg. He can state his name and knows he is in the hospital. He does not know the day of the week or the date. He recalls getting into his car the previous afternoon but has no memory of the accident or transport to the hospital. His speech is so rapid that his words are nearly incomprehensible. He sits up impulsively and almost falls out of bed. The rest of his neurological examination, including cranial nerves, motor, reflexes, sensory, and coordination, is intact.
Laboratory and imaging studies
Results of a routine chemistry panel, complete blood cell count, and coagulation studies are unremarkable. Imaging reveals right arm, left femur, and pelvic fractures. A head CT scan is normal. CT angiography of the neck does not show carotid or vertebral arterial injury. Brain MRI T2 images are normal, but T2 gradient echo (GRE) sequences reveal hypodense lesions in both frontal lobes, the left temporal lobe, and cerebellum (Figure 1 and Figure 2).
The following day, the patient undergoes surgical fixation of his limb fractures. By the fifth hospital day, he is fully oriented. His speech has more normal pacing. He still has no recollection of the accident. His girlfriend reports that his behavior is almost normal. The patient is discharged to home to follow up in orthopedic and neurology clinics.
To what diagnosis do the T2 GRE images point? >>
DIAGNOSIS: DIFFUSE AXONAL INJURY
Traumatic brain injury (TBI) is defined as a blow or penetrating head injury that affects brain function. In the US, approximately 1.7 million cases of TBI occur every year, resulting in 235,000 hospitalizations and $48 to $56 billion in costs. TBI is more common in males (78.8%) than in females (21.2%). More than half of TBI cases result from motor vehicle accidents. Each year, about 50,000 people die of TBI. It is the number one cause of death and morbidity in young adults.1
Approximately three-quarters of head injuries are categorized as “mild” TBI or “concussion.”2 Common symptoms include headache and neck pain, but other symptoms may occur as well. These include ageusia, anosmia, behavioral abnormalities, bradyphrenia, dizziness, fatigue, impaired memory, tinnitus, nausea, and vomiting. Symptoms may persist longer than a year. Repeated mild TBI may result in chronic traumatic encephalopathy.3
Concussion is generally diagnosed after TBI when patients have neurologic symptoms but lack abnormalities on routine brain CT and MRI scans. Persistent symptoms may seem inexplicable in the face of normal neuroimaging results. However, patients with mild TBI may suffer acute brain injury termed diffuse axonal injury (DAI), also known as “shearing injury,” which is not visible on standard CT and MRI scans. DAI is defined as “diffuse damage to axons in the cerebral hemispheres, in the corpus callosum, in the brainstem, and sometimes also in the cerebellum resulting from a head injury.”4
DAI results from high-impact, acceleration-deceleration forces that deform and stretch the brain. Once DAI occurs, secondary changes may include inflammation, cellular death, synaptic dysfunction, activation of glial cells, and protein deposition.1
Special MRI sequences may reveal DAI, which is characterized by microhemorrhages and edema. For example, T2 GRE is more sensitive than conventional MRI to detect microhemorrhages.2 In this patient, routine CT and MRI sequences were unremarkable, but GRE images revealed multiple hypodense areas consistent with Adams grade 1 DAI (Figures1 and 2).
Several other MRI sequences may reveal DAI. These include susceptibility weighted images (SWI), diffusion-weighted images (DWI) paired with apparent diffusion coefficient (ADC) maps, and diffusion tensor images (DTI).
The severity of DAI can be graded with the Adams classification, which was derived from histopathological post-mortem evaluation of 434 cases of fatal non-missile head injury4:
• Grade 1: axonal injury in the cerebral hemisphere white matter, corpus callosum, brainstem, and cerebellum
• Grade 2: grade 1 plus focal lesion in the corpus callosum
• Grade 3: grade 2 plus focal lesion in the rostral brainstem
In a systematic review and meta-analysis of patients with TBI, DAI increased the risk of an unfavorable outcome by 3 times.5 Furthermore, each Adams grade on MRI increased the risk of unfavorable outcome by 3 times. Consequently, a grade 3 lesion with brainstem lesions predicted a 9 times increased risk of an unfavorable outcome. However, DAI does not always result in an adverse outcome-37% of patients with grade 3 DAI had a favorable outcome.
• Neurological symptoms and signs and behavioral changes commonly occur after TBI.
• In mild TBI, DAI may be present but invisible on routine brain CT and MRI imaging.
• MRI sequences such as T2 GRE, SWI, DWI/ADC, and DTI should be considered when DAI is suspected.
• The presence of DAI indicates brain injury and increases the risk of a worse functional outcome.
• Currently, there is no proven medical treatment other than supportive care that improves prognosis in mild TBI.
*Details of this case were significantly changed to protect patient confidentiality.
About the author
Andrew Wilner, MD, is a neurologist who blogs at www.andrewwilner.com/blog. His latest book is The Locum Life: A Physician’s Guide to Locum Tenens.
1. Grassi DC, da Conceicao DM, da Costa Leite C, Andrade CS. Current contribution of diffusion tensor imaging in the evaluation of diffuse axonal injury. Arq Neuropsiquiatr. 2018;76:189-199.
2. Xiong KL, Zhu YS, Zhang WG. Diffusion tensor imaging and magnetic resonance spectroscopy in traumatic brain injury: a review of recent literature. Brain Imaging Behav. 2014;8:487-496.
3. Nisenbaum EJ, Novikov DS, Lui YW. The presence and role of iron in mild traumatic brain injury: an imaging perspective. J Neurotrauma. 2014;31:301-307.
4. Adams JH, Doyle D, Ford I, et al. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology. 1989;15:49-59.
5. Van Eijck MM, Schoonman GG, van der Naalt J, et al. Diffuse axonal injury after traumatic brain injury is a prognostic factor for functional outcome: a systemic review and meta-analysis. Brain Injury. 2018;32:395-402.