CHAPTER FOUR
TRAUMATIC BRAIN INJURY AND INCREASED INTRACRANIAL PRESSURE

CEREBRAL CONTUSIONS, DIFFUSE AXONAL INJURY, AND THE SHAKEN BABY SYNDROME

CEREBRAL CONTUSIONS

Contre coup contusions

A contusion is hemorrhagic necrosis of brain tissue. When the head is abruptly brought to a stop against a solid object, such as the dashboard or the ground, the brain continues to move for an instant, hitting the inside the now stationary skull. The soft brain is easily contused and lacerated by the hard bony ridges at the base of the skull or by the tentorium cerebelli and falx cerebri. Contusions usually involve the surface of the brain, especially the crowns of gyri, and are more frequent in the orbital surfaces of the frontal lobes and the tips of the temporal lobes. Acute contusions show hemorrhagic necrosis and brain swelling. Gradually, macrophages remove necrotic brain tissue and blood. Eventually, the contusion evolves into a yellowish plaque characterized by loss and atrophy of brain tissue, glial scarring, hemosiderin deposition, and loss of axons in the underlying white matter. A cerebral contusion can be distinguished from a cerebral infarct because, in the infarct, the superficial cortex is usually preserved, whereas in the contusion, it is the first to be destroyed. Contusions may correspond to the site of impact ("coup" contusions) -from the French word "blow"- or develop opposite the impact ("contre coup" contusions). In falls, contre coup are more frequent than coup contusions. A fall to the back with the occiput hitting the ground causes contusions in the inferior frontal and temporal lobes.

DIFFUSE AXONAL INJURY

Diffuse axonal injury (DAI) is a special traumatic lesion, which occurs most frequently in motor vehicle accidents and following blows to the unsupported head. In the course of such injuries, the cerebrum goes into a back and forth gliding motion, pivoting around the upper brainstem. The brainstem, together with the cerebellum, is held firmly fixed by the tentorium, and the falx prevents side-to-side motion. Axons are stretched but do not snap from this injury; their sudden deformation causes changes in the axonal cytoskeleton (compaction of neurofilaments, loss of microtubules) that lead to an arrest of the fast axoplasmic flow. Components of this flow, including mitochondria and other organelles, accumulate proximal to the lesion and cause axonal swellings. Some axons with mild lesions probably recover but many eventually rupture. It takes several hours from trauma to axonal rupture. The cascade of reactions that lead to the formation of axonal swellings is probably initiated by influx of calcium through the stretched axolemma. The swellings are located at nodes of Ranvier where the axolemma is more liable to deform because there is no myelin. Brain damage is most severe along midline structures (corpus callosum, brainstem) where the shear forces are greatest, and at the cortex-white matter junction because of the change in the consistency of brain tissue.

Clinically, patients with severe DAI become unconscious immediately after the injury and either remain comatose or go into a persistent vegetative state. Cerebral concussion is thought to be a mild form of DAI without permanent pathology. The loss of consciousness in concussion is probably due to a functional disturbance of the reticular activating substance of the upper brainstem. This is the part of the CNS that is subjected to the highest twisting force during sagittal rotation of the hemispheres. In severe TBI, DAI is compounded by widespread vascular injury and other traumatic lesions which cause cerebral edema and HIE.

DAI-corpus callosum hemorrhages	DAI-brainstem hemorrhages

DAI is rarely a pure lesion, and, clinically, its effects are difficult to separate from other concurrent  TBI pathology. When severe, it can depress consciousness in the acute phase and can cause lasting impairment of memory and cognition. The MRI shows small hypointense lesions corresponding to traumatic microbleeds. While being the only marker of DAI, the microbleeds may not correlate with the degree of axonal damage. In acute DAI, the brain is either normal or shows petechial hemorrhages in the corpus callosum, centrum semiovale, dorsolateral brainstem, and other areas, due to tearing of blood vessels. These vascular lesions should be distinguished from secondary brainstem hemorrhages that occur with herniations (see further on).

DAI-axonal swellings. BAPP immunostain.	DAI. Severe white matter degeneration.

Microscopically, the damaged white matter shows axonal swellings. These can occur anywhere but are particularly common in the parasagittal parts of the brain, the corpus callosum, fornix, internal capsule, and the brain stem. Axonal swellings can be detected with H&E and silver stains 15 hours after the injury. Immunostains with antibodies to Beta Amyloid Precursor Protein (BAPP) can detect the axonal lesions in 2-3 hours after the injury. BAPP is produced by neurons as a reaction to injury. It flows down the axon and accumulates at points of axonal constriction or transection. Axonal swellings may persist for years. Distal to the swellings, axons and myelin degenerate and gliosis develops over time. Severe DAI may cause decrease of white matter volume, atrophy of the corpus callosum, and dilatation of the lateral ventricles. Some patients with severe TBI and DAI also have neuronal loss and microglial nodules in the cortex, deep nuclei and brainstem (diffuse neuronal injury.)

CEREBRAL CONCUSSION is characterized by transient loss of consciousness and post-traumatic amnesia of variable duration, in most cases less than 30 minutes. Its pathology is difficult to establish because there is no opportunity for neuropathological observations. It had been thought to be a reversible functional disturbance without structural damage. However, it is now proposed that there is a continuum of brain injury in concussion, ranging from very mild cases in which patients are dazed for a few seconds without losing consciousness to the most severe ones in which there are persistent neurological abnormalities and structural changes that blend with DAI. In that sense, classic cerebral concussion is a mild form of DAI. Loss of neurological function is probably caused by axonal dysfunction. Loss of consciousness, in particular, may be due to dysfunction of the reticular activating substance of the upper brainstem. This is the part of the CNS that is subjected to the highest twisting force during sagittal rotation of the hemispheres. More important, it has become evident that repeated concussion, especially before symptoms from the previous one resolve, have a cumulative effect and can cause chronic traumatic encephalopathy.

CHRONIC TRAUMATIC ENCEPHALOPATHY

It has been known for many years that boxers develop a form of neurodegeneration that has been called the “punch-drunk” state and “dementia pugilistica”. This condition has been reported recently in professional football players and renamed “Chronic Traumatic Encephalopathy” (CTE). In addition to boxers and football players, CTE has been reported in other athletes involved in collision sports and in a few non-athletes with a history of TBI. The syndrome of CTE begins insidiously, usually many years after the patients have stopped playing sports, with inattention, mood and behavior disturbances, confusion, and memory loss, and progresses inexorably over many years to a stage of full blown dementia and parkinsonism. The brain, in CTE, shows atrophy, dilatation of the lateral and third ventricles, and thinning of the corpus callosum. Microscopic examination reveals neuronal loss and tau deposition in neurons (neurofibrillary tangles-NFTs, neuropil neurites) and in astrocytes. This pathology involves the cerebral cortex, white matter, deep nuclei, and the brainstem. In the cortex, the changes are patchy and affect the superficial cortex, perivascular areas, and deeper parts of cerebral sulci.  Beta amyloid deposition in the form of diffuse and less frequently neuritic plaques is seen inconstantly. It is clear that tau deposition is the key cellular change in CTE. The cause of CTE is thought to be TBI, especially repeated cerebral concussions and subconcussive trauma. In the acute phase, concussion, especially following side-to-side hits to the head, causes DAI and triggers the release of tau and beta amyloid in the brain. This, along with cerebral hypoxia, excitotoxicity and inflammatory mediators, set in motion a progressive destructive cascade that causes neurodegeneration many years later.

THE SHAKEN BABY SYNDROME

Shaken baby syndrome. Retinal and optic nerve hemorrhages.	Shaken baby syndrome. Retinal and optic nerve hemorrhages.

The term shaken baby syndrome (SBS) describes a pattern of child abuse which is the second most common cause of death in children under one year of age, after the sudden infant death syndrome.

Grabbing an infant by the shoulders and shaking or jerking sets the head into a whiplash or dangling motion. Acceleration and deceleration of the brain causes severe traumatic brain injury. While shaking is emphasized, in actuality, many child abuse injuries are a combination of shaking and blunt impact, and the latter is also important in their pathogenesis. Thus, the term "shaking-impact syndrome" is closer to reality. Infants with these injuries are usually brought to the Emergency Department with a nonspecific clinical picture of hypotonia, listlesness, vomiting, irritability, and lethargy. Many are apneic and comatose or are dead on admission. The diagnosis may be missed unless a skeletal survey and fundoscopic examination are done.

The SBS is characterized by a combination of subdural hematoma, subarachnoid hemorrhage, contusions, DAI, retinal hemorrhage, ischemic infarcts, global HIE, and increased intracranial pressure. The subdural hematomas are located in the interhemispheric fissure or over the convexities and may be of varying ages. DAI may affect the cortex-white matter junction, the corpus callosum, internal capsule, or the brainstem. Vascular tears from shaking cause microscopic or large parenchymal hemorrhages. Infarcts in an irregular geographic pattern are common, and global HIE results from cardiorespiratory arrest. Apnea, in turn, may be due injury of the lower brainstem and cervical spinal cord during shaking. The cause of death in most cases is increased intracranial pressure from cerebral edema associated with HIE and infarcts and the added volume of subdural hematoma. Shaking can also cause whiplash spinal cord injury. SBS infants usually also have rib, skull, and other fractures (often of varying ages), skin and soft tissue bruises, internal injuries, and other evidence of trauma. Retinal hemorrhages, often large and confluent, are an important component of the SBS and correlate with the severity of brain damage. They are probably caused by shaking of the globe and tearing of delicate retinal vessels. Documentation of retinal hemorrhage by fundoscopic examination is important in the clinical evaluation of the SBS. Retinal hemorrhages are uncommon in accidental brain injury and are infrequently seen in patients with bleeding disorders, angiopathies, sepsis, and other nontraumatic settings.

INTRACEREBRAL HEMATOMA

Severe head trauma can also cause deep intracerebral hematomas and brain necrosis. Traumatic intracerebral hematomas are often multiple. They are found more commonly in the frontal and temporal white matter. They are probably due to rupture of intrinsic vessels as result of angular rotation of the brain.

POSTTRAUMATIC CEREBRAL ISCHEMIA

A large proportion of patients with severe or fatal TBI also have cerebral infarcts. Most of these infarcts are in vascular territories and a few affect watershed zones. The underlying causes are intracranial hypertension, vascular compression from herniations, vasospasm, traumatic vascular tears, dissecting hematomas and other vascular lesions. Global HIE is also a frequent finding in severe TBI. It is caused by a combination of systemic hypotension and intracranial hypertension, leading to cerebral hypoperfusion. Cardiovascular collapse and other systemic changes may result from the effects of DAI on the medulla. Infarcts and HIE greatly increase morbidity and mortality in TBI.

Further reading

Marino R, Gasparotti R, Manzoni D, et al. Posttraumatic cerebral infarction in patients with moderate or severe head trauma. Neurology 2006;67:1165-71. PubMed

Case ME. Inflicted Traumatic Brain Injury in Infants and Young Children. Brain Pathology 2008;18:571-82. PubMed

McKee AC, Cantu RC, Nowwinski CJ, et al. Chronic Traumatic Encephalopath in Athletes: Progressive Tauopath  After Repetitive Head Injury. J Neuropathol Exp Neurol 2009;68:709-35. PubMed

Updated: November, 2009.