Intracranial Diffuse Axonal Injury at Autopsy*

JOHN R. PARKER, JOSEPH C. PARKER, JR., M.D., and JOHN C. OVERMAN, M.D.

Department of Pathology, Truman Medical Center, Kansas City, MO 64108

ABSTRACT

An illustrative case of diffuse axonal injury (DAI) emphasizes features that help to separate focal outer head trauma owing to blows and/or falls from angular acceleration head injuries associated with diffuse inner brain lesions. In the past, explaining significant neurological deficits and death as the result of diffuse closed head trauma received from high-speed auto mobile accidents has been difficult as well as confusing. The long term consequences from such diffuse inner cerebral trauma are still poorly defined. Head injuries sustained in automobile accidents have been associated with diffuse brain damage characterized by axonal injury at the moment of impact. The reported victim of a motor vehicle accident showed post-mor- tem findings for both inner cerebral trauma and focal outer cerebral dam age. The diffuse degeneration of cerebral white matter is associated with sagittal and lateral acceleration with centroaxial trauma and has a different pathogenesis from outer focal head trauma, typified by subdural hema tomas and coup injuries. Unlike outer cerebral injury, over 50 percent of victims with diffuse axonal injury die within two weeks. These individuals characteristically have no lucid interval and remain unconscious, vegeta tive, or severely disabled until death. Compared to head trauma victims without diffuse axonal injury, there is a lower incidence of skull fractures, subdural hemorrhages, or other intracranial mass effect as well as outer brain contusions. Primary brainstem injuries often demonstrated at autopsy are seen in the reported victim. Diffuse axonal injury is produced by various angles of acceleration with prolonged acceleration/deceleration usually accompanying traffic accidents. Less severe diffuse axonal injury causes concussion.

Introduction * Presented in part at the annual meeting of the .1 1 . r 1 1 ■ • Association of Clinical Scientists in Charlottesville, While mechanisms for head injury are VA, in May, 1989. complex, the lesions can be classified as 220 0091-7370/90/0600-0220 $00.90 © Institute for Clinical Science, Inc. INTRACRANIAL DIFFUSE AXONAL INJURY AT AUTOPSY 2 2 1

either focal or diffuse. Focal head injury, while lateral acceleration is the trauma, which typically occurs over the most devastating. More severe injuries outer brain surfaces, includes cerebral tear many deep axons resulting in imme contusions, subdural hemorrhages, and diate coma. epidural hemorrhages, and may be asso From primate studies and case ciated with skull fractures.4 On the other reports, it appears that diffuse axonal hand, diffuse inner brain injuries are injury is caused by direct damage to fundamentally different and are referred axons at the moment of injury. This is the to as diffuse axonal injury (DAI).4 A vic most common cause of traumatic coma in tim of a motor vehicle accident will illus the absence of an intracranial expanding trate this phenomenon and is used to lesion2 and is illustrated herein by an compare these two fundamental types of automobile accident victim. closed, blunt head trauma. Diffuse axonal injury is demonstrated microscopically by damage to vast Case Report numbers of axons (neurites) throughout R. K., a previously healthy 17-year-old white male, the inner brain and grossly by hemor was a passenger in a half ton piek-up truck which rhagic lesions in the corpus callosum and struck a parked vehicle at an unknown rate of speed. The impact was sufficient to crush the front of the dorsolateral quadrants of the rostral truck. R. K. presented at Truman Medical Center- brainstem.7 The severity of neuropatho- West in Kansas City, MO., unconscious with dilated logical abnormalities, the duration of and fixed pupils. His extremities had numerous abrasions and were cyanotic. He did not respond to coma, and prognosis for recovery corre vasopressor agents, fluids, or other resuscitation spond with the direction of head move efforts and died within hours of the accident. ment at the initial insult. Primate stud The medical examiner’s autopsy revealed evidence of massive blunt head trauma. A large abrasion cov ies7 have shown that sagittal acceleration ered the right superior and lateral orbit, right tem produces the least amount of long-term ple, right cheek, right lower mandible, and right

F ig u r e 1. Diffuse axonal injury manifested by petechial lesions in the corpus callosum. 2 2 2 PARKER, PARKER, AND OVERMAN

neck. Reflection of the scalp revealed a scalp contu Discussion sion 4.5 cm in diameter over the right temple. The dura was intact with diffuse subarachnoid hemor rhages over the right and left cerebral convexities. Diffuse axonal injury, a term posed by No subdural hemorrhage was identified. There were Adams,5 has many confusing synonyms, multiple skull fractures including a basilar fracture involving the right middle fossa and another radiat including “intermediary coup” lesions,8 ing from the right anterior fossa across the sella tur shearing or rotational injuries, diffuse cica into the left middle fossa. degeneration of cerebral white matter,10 Other autopsy findings included multiple lung contusions over the lateral and posterior aspects of inner cerebral trauma, and diffuse white the upper and lower lobes of the left lung. The right matter shearing injury.12 Injuries severe lung was atelectatic secondary to pneumothorax. No enough to produce diffuse axonal injury traumatic injury of the heart or aorta was present. No intra-abdominal trauma was identified. are seen most commonly as a result of The neuropathological examination revealed a automobile accidents.6 Unless an indi recent contusion over the inferior temporal lobes and vidual falls from a considerable height, the inferior aspects of the frontal lobes. Diffuse sub arachnoid hemorrhage was present over the right falls do not produce diffuse axonal temporoparietal region. Diffuse edema was mani injury.3 Studies4,9 have shown that fested by flattened gyri and narrowed sulci. The patients who suffer diffuse axonal injury brain, coronally sectioned at 2.5 cm intervals, showed rotational and/or shearing injury manifested do not sustain skull fractures, cerebral by punctate hemorrhages in the corpus callosum and contusions, intracranial hematoma, or basal ganglia (figure 1). Multiple brainstem hemor sudden cerebral edema as often as those rhages were present (figure 2). Histological section ing revealed axonal spheroids in these hemorrhagic who sustain only outer focal cerebral areas (figure 3). damage (table I). Subarachnoid hemor-

F ig u r e 2 . D iffu se axonal injury with small hemorrhages in the rostral brainstem. INTRACRANIAL DIFFUSE AXONAL INJURY AT AUTOPSY 223

axonal injury has been detected in child abuse cases. In the study by Vowles, dif fuse axonal injury was present in every case of contusional tearing.11 Shaking and blunt force injuries are the most common mechanisms of injury in infants. This pattern of injury is in striking contrast to that associated with a low fall. The duration of acceleration is appar ently much shorter than in automobile crashes. This shorter duration of acceler ation combined with a lesser propensity for total frontal injury in low falls, results in a different pattern of injury character ized by focal lesions over the outer sur face of the brain. Skull fractures, sub dural hematomas, and brain contusions (classically of contracoup type) are com mon after low falls, while the instance of DAI is very low (table I). Nevertheless, many victims of closed head trauma, as seen in the reported case, experience varying combinations of both outer focal contusions and DAI. Clinical correlation with detailed descriptions of the injury are required to assess accurately these intracranial lesions. FIGURE 3. Axonal swellings (see arrow) indicative of diifuse axonal injury (Bielchowsky stain, 250 x). T A B L E I

Comparison of Blunt Head Trauma rhage is also uncommon in victims with to Diffuse Axonal Injury* only DAI. Patients with lethal diffuse axonal injury usually have an immediate In n e r O uter (Diffu s e loss of consciousness, evolving into a (Focal) o r DAI) deep coma.9 Coma from the moment of insult has been assumed as a clinical pre Clinical Circumstances Falls 1. High + ++ requisite of diffuse axonal injury.6 2. L o w ++ + The production and severity of the Blows 1. Angular + ++ 2. L i n e a r + + lesions seen in diffuse axonal injury High Speed Injuries + ++ C o m a + ++ depend on many factors, including the Early Death + ++ magnitude, duration, and direction of M o r p h o l o g y acceleration.7 Animal models7 have Epidural Hematoma ++ 0 shown that acceleration in the sagittal Subdural Hemorrhage ++ 0 Subarachnoid Hemorrhage ++ 0 plane causes moderate disability in Coup/Contracoup ++ 0 Periventricular Hemorrhages 0 ++ behavior and motor skills; however, Periaqueductal Hemorrhages 0 ++ recovery is slow and incomplete. Skull Fracture ++ + Lateral and oblique insults yield a prolonged coma duration and much *Legend: ++ = often present. + = not often present. more severe motor impairment. Diffuse 0 = not typical or absent. 2 2 4 PARKER, PARKER, AND OVERMAN In our case study, lesions in the corpus References callosum and dorsolateral quadrants of the brainstem are indicative of diffuse 1. A d a m s , J. H.: Head Injury, in Adams, J. H., Corsellis, J. A. N., and Duchen, L. W., (eds). axonal injury. Histologically, acute Greenfield’s Neuropathology, 4th ed. London, changes include diffuse damage to neur- Edward Arnold, 1984, pp. 85-124. ites with axonal retraction balls and vari 2. A d a m s , J. H., et al: Microscopic diffuse axonal injury in cases of head injury. Medical Science cosities.1 With time, reactive changes Law 25:265-269, 1985. include microglial nodules throughout 3. A d a m s , J. H., D o y l e , D., et al: Diffuse axonal the white matter in the cerebrum, cere injury in head injuries caused by a fall. Lancet bellum and brainstem.1 Myelin may 2:1420-1421, 1984. 4. A d a m s , J. H. and G r a h a m , D. I.: Diffuse brain become distorted, and the axonal swell damage in non-missile head injury, in Anthony, ings may persist. After several months, P. P. and MacSween, R. N. M. (eds.) Recent Wallerian degeneration of the medial Advances in Histopathology, vol. 12. Edin burgh, Churchill, Livingstone, 1984, pp. leminisci, pyramidal tracts, internal cap 241-257. sule, and cerebral white matter is seen.1 5. A d a m s, J. H., G raham , D . I., M urray, L. S ., At autopsy, acute diffuse axonal injury an d S c o t t , G.: Diffuse axonal injury due to non missile head injury in humans: An analysis of 45 manifests itself as hemorrhagic lesions cases. Ann. Neurol. 12:557-563, 1982. (streaks, petechiae, or ball hemor 6. C o r d o b é s , F., L o b a t o , R. D. et al: Post-trau rhages). Over months to years, the hem matic diffuse axonal brain injury. Analysis of 78 patients studies with Computerized Tomogra orrhagic lesions become lytic, cavitated, phy. Acta Neurochirug. 81:27-35, 1986. gliotic, and demyelinated. 7. G e n n a r e l l i, T. A., et al: Diffuse axonal injury Proper fixation is imperative for recog and traumatic coma in the primate. Ann. nition of acute diffuse axonal injury. The Neurol. i2:564-574, 1982. 8. L in d e n b e r g , R.: Trauma of meninges and brain. characteristic lesions may be missed if Pathology of the Nervous System, vol. 2, New the brain is cut without formalin fixation. York, McGraw Hill, 1971, pp. 1705-1765. The brain should be firm enough for a 9. S im p s o n , R. H. W. and B e r s o n , S. D. The detailed and thorough macroscopic postmortem diagnosis of diffuse cerebral inju ries, with special reference to the importance of examination.9 Since some cases of diffuse brain fixation. South African Med. J. 71:10-14, axonal injury do not show characteristic 1987. macroscopic findings, microscopic sec 10. St r it c h , S . J.: Diffuse degeneration of the cere bral white matter in severe dementia following tions from susceptible areas such as the head injury. J. Neurol. Neurosurg. and Psychiat. corpus callosum, hypothalamus, and 19:163-185, 1956. midbrain should be examined. 11. V o w l e s , G. H., Sc h o l t z , C. L., and C a m e r o n , J. M.: Diffuse axonal injury in early infancy. J. Clin. Pathol. 40:185-189, 1987. Acknowledgments 12. Z im m e r m a n , R. A., B il a n iu k , L. T., and G e n Thanks are extended to Robert T. Burns, HT and n a r e l l i, T. A.: Computed tomography of shear Jane Hulme for their technical assistance in prepar ing injuries of the cerebral white matter. Radiol ing this manuscript. ogy 127:393-396, 1978.