Harrison's Neurology in Clinical Medicine, 3rd Edition


Allan H. Ropper

Almost 10 million head injuries occur annually in the United States, about 20% of which are serious enough to cause brain damage. Among men <35 years, accidents, usually motor vehicle collisions, are the chief cause of death and >70% of these involve head injury. Furthermore, minor head injuries are so common that almost all physicians will be called upon to provide immediate care or to see patients who are suffering from various sequelae.

Medical personnel caring for head injury patients should be aware that (1) spinal injury often accompanies head injury, and care must be taken in handling the patient to prevent compression of the spinal cord due to instability of the spinal column; (2) intoxication is a common accompaniment of traumatic brain injury and, when appropriate, testing should be carried out for drugs and alcohol; and (3) additional injuries, including rupture of abdominal organs, may produce vascular collapse or respiratory distress that requires immediate attention.



This form of minor head injury refers to an immediate and transient loss of consciousness that is associated with a short period of amnesia. Many patients do not lose consciousness after a minor head injury but instead are dazed or confused, or feel stunned or “star struck.” Severe concussion may precipitate a brief convulsion or autonomic signs such as facial pallor, bradycardia, faintness with mild hypotension, or sluggish pupillary reaction, but most patients are quickly neurologically normal.

The mechanics of a typical concussion involve sudden deceleration of the head when hitting a blunt object. This creates an anterior-posterior movement of the brain within the skull due to inertia and rotation of the cerebral hemispheres on the relatively fixed upper brainstem. Loss of consciousness in concussion is believed to result from a transient electrophysiologic dysfunction of the reticular activating system in the upper midbrain that is at the site of rotation (Chap. 17).

Gross and light-microscopic changes in the brain are usually absent following concussion but biochemical and ultrastructural changes, such as mitochondrial ATP depletion and local disruption of the blood-brain barrier, are transient abnormalities. CT and MRI scans are usually normal; however, a small number of patients will be found to have a skull fracture, an intracranial hemorrhage, or brain contusion.

A brief period of both retrograde and anterograde amnesia is characteristic of concussion and it recedes rapidly in alert patients. Memory loss spans the moments before impact but may encompass the previous days or weeks (rarely months). With severe injuries, the extent of retrograde amnesia roughly correlates with the severity of injury. Memory is regained from the most distant to more recent memories, with islands of amnesia occasionally remaining. The mechanism of amnesia is not known. Hysterical posttraumatic amnesia is not uncommon after head injury and should be suspected when inexplicable behavioral abnormalities occur, such as recounting events that cannot be recalled on later testing, a bizarre affect, forgetting one’s own name, or a persistent anterograde deficit that is excessive in comparison with the degree of injury. Amnesia is discussed in Chap. 18.

A single, uncomplicated concussion only infrequently produces permanent neurobehavioral changes in patients who are free of preexisting psychiatric and neurologic problems. Nonetheless, residual problems in memory and concentration may have an anatomic correlate in microscopic cerebral lesions (later in the chapter).


A surface bruise of the brain, or contusion, consists of varying degrees of petechial hemorrhage, edema, and tissue destruction. Contusions and deeper hemorrhages result from mechanical forces that displace and compress the hemispheres forcefully and by deceleration of the brain against the inner skull, either under a point of impact (coup lesion) or, as the brain swings back, in the antipolar area (contrecoup lesion). Trauma sufficient to cause prolonged unconsciousness usually produces some degree of contusion. Blunt deceleration impact, as occurs against an automobile dashboard or from falling forward onto a hard surface, causes contusions on the orbital surfaces of the frontal lobes and the anterior and basal portions of the temporal lobes. With lateral forces, as from impact on an automobile door frame, contusions are situated on the lateral convexity of the hemisphere. The clinical signs of contusion are determined by the location and size of the lesion; often, there are no focal neurologic abnormalities, but these injured regions are later the sites of gliotic scars that may produce seizures. A hemiparesis or gaze preference is fairly typical of moderately sized contusions. Large bilateral contusions produce stupor with extensor posturing, while those limited to the frontal lobes cause a taciturn state. Contusions in the temporal lobe may cause delirium or an aggressive, combative syndrome.

Contusions are easily visible on CT and MRI scans, appearing as inhomogeneous hyperdensities on CT and as hyperintensities on MRI sequences that detect blood; there is usually localized brain edema (Fig. 36-1) and some subarachnoid bleeding. Blood in the cerebrospinal fluid (CSF) due to trauma may provoke a mild inflammatory reaction. Over a few days, contusions acquire a surrounding contrast enhancement and edema that may be mistaken for tumor or abscess. Glial and macrophage reactions result in chronic, scarred, hemosiderin-stained depressions on the cortex (plaques jaunes) that are the main source of posttraumatic epilepsy.



Traumatic cerebral contusion. Noncontrast CT scan demonstrating a hyperdense hemorrhagic region in the anterior temporal lobe.

Torsional or shearing forces within the brain cause hemorrhages of the basal ganglia and other deep regions. Large hemorrhages after minor trauma suggest that there is a bleeding diathesis or cerebrovascular amyloidosis. For unexplained reasons, deep cerebral hemorrhages may not develop until several days after injury. Sudden neurologic deterioration in a comatose patient or a sudden rise in intracranial pressure (ICP) suggests this complication and should therefore prompt investigation with a CT scan.

A special type of deep white matter lesion consists of widespread mechanical disruption, or shearing, of axons at the time of impact. Most characteristic are small areas of tissue injury in the corpus callosum and dorsolateral pons. The presence of widespread axonal damage in both hemispheres, a state called diffuse axonal injury (DAI), has been proposed to explain persistent coma and the vegetative state after closed head injury (Chap. 17), but small ischemic-hemorrhagic lesions in the midbrain and thalamus are as often the cause. Only severe shearing lesions that contain blood are visualized by CT, usually in the corpus callosum and centrum semiovale (Fig. 36-2); however, selective imaging sequences of the MRI can demonstrate such lesions throughout the white matter.



Multiple small areas of hemorrhage and tissue disruption in the white matter of the frontal lobes on noncontrast CT scan. These appear to reflect an extreme type of the diffuse axonal shearing lesions that occur with closed head injury.


A blow to the skull that exceeds the elastic tolerance of the bone causes a fracture. Intracranial lesions accompany roughly two-thirds of skull fractures and the presence of a fracture increases many-fold the chances of an underlying subdural or epidural hematoma. Consequently, fractures are primarily markers of the site and severity of injury. They also provide potential pathways for entry of bacteria to the CSF with a risk of meningitis and for leakage of CSF outward through the dura. Severe orthostatic headache results from lowered pressure in the spinal fluid compartment.

Most fractures are linear and extend from the point of impact toward the base of the skull. Basilar skull fractures are often extensions of adjacent linear fractures over the convexity of the skull but may occur independently owing to stresses on the floor of the middle cranial fossa or occiput. Basilar fractures are usually parallel to the petrous bone or along the sphenoid bone and directed toward the sella turcica and ethmoidal groove. Although most basilar fractures are uncomplicated, they can cause CSF leakage, pneumocephalus, and cavernous-carotid fistulas. Hemotympanum (blood behind the tympanic membrane), delayed ecchymosis over the mastoid process (Battle sign), or periorbital ecchymosis (“raccoon sign”) are associated with basilar fractures. Because routine x-ray examination may fail to disclose basilar fractures, they should be suspected if these clinical signs are present.

CSF may leak through the cribriform plate or the adjacent sinus and cause CSF rhinorrhea (a watery discharge from the nose). Persistent rhinorrhea and recurrent meningitis are indications for surgical repair of torn dura underlying the fracture. The site of the leak is often difficult to determine, but useful diagnostic tests include the instillation of water-soluble contrast into the CSF followed by CT with the patient in various positions, or injection of radionuclide compounds or fluorescein into the CSF and the insertion of absorptive nasal pledgets. The location of an intermittent leak is rarely delineated, and many resolve spontaneously.

Sellar fractures, even those associated with serious neuroendocrine dysfunction, may be radiologically occult or evident only by an air-fluid level in the sphenoid sinus. Fractures of the dorsum sella cause sixth or seventh nerve palsies or optic nerve damage.

Petrous bone fractures, especially those oriented along the long axis of the bone, may be associated with facial palsy, disruption of ear ossicles, and CSF otorrhea. Transverse petrous fractures are less common; they almost always damage the cochlea or labyrinths and often the facial nerve as well. External bleeding from the ear is usually from local abrasion of the external canal but can also result from petrous fracture.

Fractures of the frontal bone are usually depressed, involving the frontal and paranasal sinuses and the orbits. Depressed skull fractures are typically compound, but they are often asymptomatic because the impact energy is dissipated in breaking the bone; some have underlying brain contusions. Debridement and exploration of compound fractures are required in order to avoid infection; simple fractures do not require surgery.


The cranial nerves most often injured with head trauma are the olfactory, optic, oculomotor, and trochlear; the first and second branches of the trigeminal nerve; and the facial and auditory nerves. Anosmia and an apparent loss of taste (actually a loss of perception of aromatic flavors, with retained elementary taste perception) occur in ~10% of persons with serious head injuries, particularly from falls on the back of the head. This is the result of displacement of the brain and shearing of the fine olfactory nerve filaments that course through the cribriform bone. At least partial recovery of olfactory and gustatory function is expected, but if bilateral anosmia persists for several months, the prognosis is poor. Partial optic nerve injuries from closed trauma result in blurring of vision, central or paracentral scotomas, or sector defects. Direct orbital injury may cause short-lived blurred vision for close objects due to reversible iridoplegia. Diplopia limited to downward gaze and corrected when the head is tilted away from the side of the affected eye indicates trochlear (fourth nerve) nerve damage. It occurs frequently as an isolated problem after minor head injury or may develop for unknown reasons after a delay of several days. Facial nerve injury caused by a basilar fracture is present immediately in up to 3% of severe injuries; it may also be delayed 5-7 days. Fractures through the petrous bone, particularly the less common transverse type, are liable to produce facial palsy. Delayed palsy, the mechanism of which is unknown, has a good prognosis. Injury to the eighth cranial nerve from a fracture of the petrous bone causes loss of hearing, vertigo, and nystagmus immediately after injury. Deafness from eighth nerve injury is rare and must be distinguished from blood in the middle ear or disruption of the middle ear ossicles. Dizziness, tinnitus, and high-tone hearing loss occur from cochlear concussion.


Convulsions are surprisingly uncommon immediately after a head injury, but a brief period of tonic extensor posturing or a few clonic movements of the limbs just after the moment of impact can occur. However, the cortical scars that evolve from contusions are highly epileptogenic and may later manifest as seizures, even after many months or years (Chap. 26). The severity of injury roughly determines the risk of future seizures. It has been estimated that 17% of individuals with brain contusion, subdural hematoma, or prolonged loss of consciousness will develop a seizure disorder and that this risk extends for an indefinite period of time, whereas the risk is <2% after mild injury. The majority of convulsions in the latter group occur within 5 years of injury but may be delayed for decades. Penetrating injuries have a much higher rate of subsequent epilepsy.


Hemorrhages beneath the dura (subdural) or between the dura and skull (epidural) have characteristic clinical and radiologic features. They are associated with underlying contusions and other injuries, often making it difficult to determine the relative contribution of each component to the clinical state. The mass effect and raised ICP caused by these hematomas can be life threatening, making it imperative to identify them rapidly by CT or MRI scan and to remove them when appropriate.

Acute subdural hematoma (Fig. 36-3)

Direct cranial trauma may be minor and is not required for acute subdural hemorrhage to occur, especially in the elderly and those taking anticoagulant medications. Acceleration forces alone, as from whiplash, are sometimes sufficient to produce subdural hemorrhage. Up to one-third of patients have a lucid interval lasting minutes to hours before coma supervenes, but most are drowsy or comatose from the moment of injury. A unilateral headache and slightly enlarged pupil on the side of the hematoma are frequently, but not invariably, present. Stupor or coma, hemiparesis, and unilateral pupillary enlargement are signs of larger hematomas. In an acutely deteriorating patient, burr (drainage) holes or an emergency craniotomy are required. Small subdural hematomas may be asymptomatic and usually do not require evacuation if they do not expand.



Acute subdural hematoma. Noncontrast CT scan reveals a hyperdense clot which has an irregular border with the brain and causes more horizontal displacement (mass effect) than might be expected from its thickness. The disproportionate mass effect is the result of the large rostral-caudal extent of these hematomas. Compare to Fig. 36-4.

A subacutely evolving syndrome due to subdural hematoma occurs days or weeks after injury with drowsiness, headache, confusion, or mild hemiparesis, usually in alcoholics and in the elderly and often after only minor trauma. On imaging studies subdural hematomas appear as crescentic collections over the convexity of one or both hemispheres, most commonly in the frontotemporal region, and less often in the inferior middle fossa or over the occipital poles (Fig. 36-3). Interhemispheric, posterior fossa, or bilateral convexity hematomas are less frequent and are difficult to diagnose clinically, although drowsiness and the neurologic signs expected from damage in each region can usually be detected. The bleeding that causes larger hematomas is primarily venous in origin, although additional arterial bleeding sites are sometimes found at operation, and a few large hematomas have a purely arterial origin.

Epidural hematoma (Fig. 36-4)

These evolve more rapidly than subdural hematomas and are correspondingly more treacherous. They occur in up to 10% of cases of severe head injury but are associated with underlying cortical damage less often than are subdural hematomas. Most patients are unconscious when first seen. A “lucid interval” of several minutes to hours before coma supervenes is most characteristic of epidural hemorrhage, but it is still uncommon, and epidural hemorrhage is not the only cause of this temporal sequence. Rapid surgical evacuation and ligation or cautery of the damaged vessel is indicated, usually the middle meningeal artery that has been lacerated by an overlying skull fracture.



Acute epidural hematoma. The tightly attached dura is stripped from the inner table of the skull, producing a characteristic lenticular-shaped hemorrhage on noncontrast CT scan. Epidural hematomas are usually caused by tearing of the middle meningeal artery following fracture of the temporal bone.

Chronic subdural hematoma (Fig. 36-5)

A history of trauma may or may not be elicited in relation to chronic subdural hematoma; the injury may have been trivial and forgotten, particularly in the elderly and those with clotting disorders. Headache is common but not invariable. Additional features may include slowed thinking, vague change in personality, seizure, or a mild hemiparesis. The headache fluctuates in severity, sometimes with changes in head position. Bilateral chronic subdural hematomas produce perplexing clinical syndromes and the initial clinical impression may be of a stroke, brain tumor, drug intoxication, depression, or a dementing illness. Drowsiness, inattentiveness, and incoherence of thought are more generally prominent than focal signs such as hemiparesis. Rarely, chronic hematomas cause brief episodes of hemiparesis or aphasia that are indistinguishable from transient ischemic attacks. Patients with undetected bilateral subdural hematomas have a low tolerance for surgery, anesthesia, and drugs that depress the nervous system; drowsiness or confusion persist for long periods postoperatively.



CT scan of chronic bilateral subdural hematomas of different ages. The collections began as acute hematomas and have become hypodense in comparison to the adjacent brain after a period during which they were isodense and difficult to appreciate. Some areas of resolving blood are contained on the more recently formed collection on the left (arrows).

CT without contrast initially shows a low-density mass over the convexity of the hemisphere (Fig. 36-5). Between 2 and 6 weeks after the initial bleeding the hemorrhage becomes isodense compared to adjacent brain and may be inapparent. Many subdural hematomas that are several weeks in age contain areas of blood and intermixed serous fluid. Bilateral chronic hematomas may fail to be detected because of the absence of lateral tissue shifts; this circumstance in an older patient is suggested by a “hypernormal” CT scan with fullness of the cortical sulci and small ventricles. Infusion of contrast material demonstrates enhancement of the vascular fibrous capsule surrounding the collection. MRI reliably identifies subacute and chronic hematomas.

Clinical observation coupled with serial imaging is a reasonable approach to patients with few symptoms, such as headache alone, and small chronic subdural collections. Treatment of minimally symptomatic chronic subdural hematoma with glucocorticoids is favored by some clinicians, but surgical evacuation is more often successful. The fibrous membranes that grow from the dura and encapsulate the collection require removal to prevent recurrent fluid accumulation. Small hematomas are resorbed, leaving only the organizing membranes. On imaging studies very chronic subdural hematomas are difficult to distinguish from hygromas, which are collections of CSF from a rent in the arachnoid membrane.



The patient who has briefly lost consciousness or been stunned after a minor head injury usually becomes fully alert and attentive within minutes but may complain of headache, dizziness, faintness, nausea, a single episode of emesis, difficulty with concentration, a brief amnestic period, or slight blurring of vision. This typical concussion syndrome has a good prognosis with little risk of subsequent deterioration. Children are particularly prone to drowsiness, vomiting, and irritability, symptoms that are sometimes delayed for several hours after apparently minor injuries. Vasovagal syncope that follows injury may cause undue concern. Generalized or frontal headache is common in the following days. It may be migrainous (throbbing and hemicranial) in nature or aching and bilateral. After several hours of observation, patients with minor injury may be accompanied home and observed for a day by a family member or friend; written instructions to return if symptoms worsen should be provided.

Persistent severe headache and repeated vomiting in the context of normal alertness and no focal neurologic signs is usually benign, but CT should be obtained and a longer period of observation is appropriate. The decision to perform imaging tests also depends on clinical signs that indicate the impact was severe (e.g., prolonged concussion, periorbital or mastoid hematoma, repeated vomiting, palpable skull fracture), on the seriousness of other bodily injuries, and on the degree of surveillance that can be anticipated after discharge. Two studies have indicated that older age, two or more episodes of vomiting, >30 min of retrograde or persistent antero-grade amnesia, seizure, and concurrent drug or alcohol intoxication are sensitive (but not specific) indicators of intracranial hemorrhage that justify CT scanning. It is appropriate to be more liberal in obtaining CT scans in children since a small number, even without loss of consciousness, will have intracranial lesions.

Concussion in sports

In the current absence of adequate data, a common sense approach to athletic concussion has been to avoid contact sports for at least several days after a mild injury, and for a longer period if there are more severe injuries or if there are protracted neurologic symptoms. The individual then undertakes a graduated program of activity until there are no further symptoms with exercise (Table 36-1). These guidelines are designed in part to avoid the extremely rare second impact syndrome, in which cerebral swelling follows a second minor head injury. There is some evidence that repeated concussions are associated with cumulative cognitive deficits, but this and the subsequent risk for dementia and Parkinson’s disease are controversial.

TABLE 36-1





Patients who are not fully alert or have persistent confusion, behavioral changes, extreme dizziness, or focal neurologic signs such as hemiparesis should be admitted to the hospital and have a CT scan. A cerebral contusion or hematoma is usually found. Common syndromes include: (1) delirium with a disinclination to be examined or moved, expletive speech, and resistance if disturbed (anterior temporal lobe contusions); (2) a quiet, disinterested, slowed mental state (abulia) alternating with irascibility (inferior frontal and frontopolar contusions); (3) a focal deficit such as aphasia or mild hemiparesis (due to subdural hematoma or convexity contusion, or, less often, carotid artery dissection); (4) confusion and inattention, poor performance on simple mental tasks, and fluctuating orientation (associated with several types of injuries, including those described earlier and with medial frontal contusions and interhemispheric subdural hematoma); (5) repetitive vomiting, nystagmus, drowsiness, and unsteadiness (labyrinthine concussion, but occasionally due to a posterior fossa subdural hematoma or vertebral artery dissection); and (6) diabetes insipidus (damage to the median eminence or pituitary stalk). Injuries of this degree are often complicated by drug or alcohol intoxication, and clinically inapparent cervical spine injury may be present.

After surgical removal of hematomas, most patients in this category improve over weeks. During the first week, the state of alertness, memory, and other cognitive functions often fluctuate, and agitation is common. Behavioral changes tend to be worse at night, as with many other encephalopathies, and may be treated with small doses of antipsychotic medications. Subtle abnormalities of attention, intellect, spontaneity, and memory return toward normal weeks or months after the injury, sometimes abruptly. Persistent cognitive problems are discussed later.


Patients who are comatose from the moment of injury require immediate neurologic attention and resuscitation. After intubation, with care taken to immobilize the cervical spine, the depth of coma, pupillary size and reactivity, limb movements, and Babinski responses are assessed. As soon as vital functions permit and cervical spine x-rays and a CT scan have been obtained, the patient should be transported to a critical care unit. Hypoxia should be reversed, and normal saline used as the resuscitation fluid in preference to albumin. The finding of an epidural or subdural hematoma or large intracerebral hemorrhage is an indication for prompt surgery and intracranial decompression in an otherwise salvageable patient. The use of prophylactic antiepileptic medications has been recommended but there is little supportive data. Management of raised ICP, a frequent feature of severe head injury, is discussed in Chap. 28.


In severe head injury, the clinical features of eye opening, motor responses of the limbs, and verbal output have been found to be generally predictive of outcome. These three responses are assessed by the Glasgow Coma Scale; a score between 3 and 15 is assigned (Table 36-2). Over 85% of patients with aggregate scores of <5 die within 24 h. However, a number of patients with slightly higher scores, including a few without pupillary light responses, survive, suggesting that an initially aggressive approach is justified in most patients. Patients <20 years, particularly children, may make remarkable recoveries after having grave early neurologic signs. In one large study of severe head injury, 55% of children had a good outcome at 1 year, compared with 21% of adults. Older age, increased ICP, early hypoxia or hypotension, compression of the brainstem on CT or MRI, and a delay in the evacuation of large intracranial hemorrhages are indicators of a poor prognosis.

TABLE 36-2





The postconcussion syndrome refers to a state following minor head injury consisting of fatigue, dizziness, headache, and difficulty in concentration. The syndrome simulates asthenia and anxious depression. Based on experimental models, it has been proposed that subtle axonal shearing lesions or as yet undefined biochemical alterations account for the cognitive symptoms. In moderate and severe trauma, neuropsychological changes such as difficulty with attention, memory and other cognitive deficits are undoubtedly present, sometimes severe, but many problems identified by formal testing do not affect daily functioning. Test scores tend to improve rapidly during the first 6 months after injury, then more slowly for years.

Management of the postconcussive syndrome requires the identification and treatment of depression, sleeplessness, anxiety, persistent headache, and dizziness. A clear explanation of the problems that may follow concussion has been shown to reduce subsequent complaints. Care is taken to avoid prolonged use of drugs that produce dependence. Headache may initially be treated with acetaminophen and small doses of amitryptiline. Vestibular exercises (Chap. 11) and small doses of vestibular suppressants such as promethazine (Phenergan) may be helpful when dizziness is the main problem. Patients who after minor or moderate injury have difficulty with memory or with complex cognitive tasks at work may be reassured that these problems usually improve over 6–12 months. It is sometimes helpful to obtain serial and quantified neuropsychological testing in order to adjust the work environment to the patient’s abilities and to document improvement over time. Whether cognitive exercises are useful in contrast to rest and a reduction in mental challenges is uncertain. Previously energetic and resilient individuals usually have the best recoveries. In patients with persistent symptoms, the possibility exists of malingering or prolongation as a result of litigation.