Anoxic Encephalopathy

A severe burn is attended by the rapid and massive accumulation of edema in the burned and unburned skin (burn edema). Intravascular volume depletion and hypotension follow and lead to ischemic tissue damage. This state is called burn shock . Anoxic encephalopathy is the most common neurologic complication of a burn, and burn shock is its most common cause in the first few days after a burn. After the first week, septic shock becomes the major cause.

Other Encephalopathies

Burned patients are liable to a variety of metabolic derangements, many of which cause encephalopathy. Fluid resuscitation for burn shock can result in dilutional hyponatremia, the most common cause of early confusion and seizures in burned patients, especially children. Later in the hospital course, hyponatremia is most often associated with systemic infection. Uremic encephalopathy is most often due to acute renal failure, which is common in the burn unit. In patients with chronic liver disease, hepatic encephalopathy can develop during convalescence from a burn. Precipitating causes include a systemic infection, narcotic analgesics, hypovolemia, and gastrointestinal bleeding. Hypernatremia, caused by insensible water loss through the burn wound, is the most common electrolyte abnormality. A burn causes a marked increase in metabolic rate. There is increased production of glucose, and this may lead to hyperglycemia. Insulin resistance and intravenous hyperalimentation are other causes of hyperglycemia in burned patients. Hypoglycemia is usually associated with overwhelming systemic infection. Sequestration of calcium in burned skin may cause hypocalcemia, which can lead to seizures and confusion. Hypomagnesemia, with muscle cramps or hallucinations, occurs occasionally. Septic encephalopathy, caused by systemic infection, and toxic encephalopathy, caused by sedating and analgesic medicines, are common problems in the burn unit.

Pseudomonas aeruginosa

Bacterial meningitis develops in 0.1 to 4 percent of extensively burned patients. P. aeruginosa is the most common etiology. Moreover, in one autopsy series, meningitis developed in 15 percent of burned patients who had a systemic Pseudomonas infection. A burn wound infection was the most common source, and blood cultures were positive. This is the only CNS infection that has been reported in the first week after a burn. Other gram-negative enteric organisms, such as Escherichia coli and Acinetobacter baumannii , and Staphylococcus aureus , but not fungi, have been reported to cause meningitis in burned patients. Gram-negative rods have not been reported to cause other types of intracranial infection, such as brain abscess.

The diagnosis of meningitis may be difficult because the burn surgeon will probably have started to treat the primary (source) infection by the time of neurologic consultation. This may eliminate the headache and stiff neck of meningitis without eradicating the infection. In some patients, only confusion, stupor, or coma is found. Hence, a metabolic or septic encephalopathy may be diagnosed. However, a gram-negative infection outside the CNS, especially one due to P. aeruginosa , occurring in a patient with an extensive burn that is more than 1 week old, should prompt lumbar puncture. Evidence of meningitis, perhaps partially treated, may be found. If cultures and smears of CSF are negative, antibiotics effective against P. aeruginosa meningitis should be prescribed because that is the likeliest pathogen. Many burned patients have more than one systemic infection. Adequate coverage should also be provided for meningitis due to all other microorganisms grown in systemic culture.

If the skin of the back is burned, it may be impossible to do a lumbar or cervical puncture. This is the case in the most extensively burned patients, and they are the ones most likely to develop meningitis. If such a patient has a systemic infection due to a gram-negative rod, particularly P. aeruginosa , an antibiotic with good CSF penetration should be prescribed so that meningitis, although impossible to document, should not go untreated.

Candida Species

The frequency of Candida infections is increasing among burned patients, because of the use of broad-spectrum antibiotics for bacterial infections, longer survival of older and more extensively burned patients, and the use of central intravenous catheters and intravenous hyperalimentation. Half of the patients with invasive candidiasis have cerebral involvement at autopsy. This most often takes the form of disseminated microabscesses; large abscesses, meningitis and mycotic aneurysms are much less common. Patients infected with Candida have almost always had at least one previously treated bacterial infection. This is reflected in the relatively late onset of cerebral candidiasis—usually late in the second hospital week and never in the first week.

The antemortem diagnosis of disseminated cerebral microabscesses is difficult. They typically produce drowsiness, confusion, stupor, or coma. Fixed, focal cerebral signs and seizures are unusual. The CSF remains normal. Often less than 3 mm in diameter, the abscesses are too small to be detected by computed tomography (CT), but MRI shows larger ones as small ring-enhancing lesions. Thus, it may require MRI to distinguish multiple cerebral microabscesses from a metabolic or septic encephalopathy.

The diagnosis of cerebral candidiasis may be difficult because the CSF is usually normal, and the diagnosis therefore requires the demonstration of infection outside the CNS. The primary site of infection may not be apparent, and metastatic foci of infection may be hidden as microabscesses in the myocardium or kidney. Pneumonia, evidence of which can be seen on a chest radiograph, is not common. Positive urine, sputum, fecal, and wound cultures can mean colonization rather than infection. Blood cultures are often negative. Without candidemia, the diagnosis is usually made only after death. There is currently no single test that identifies every case of invasive candidiasis. The diagnosis begins with a high index of suspicion in patients with unexplained systemic signs of infection, deep extensive burns, and a prior bacterial infection. Blood cultures, serologic tests, and repeated clinical evaluation for involvement of the skin and eye may help in diagnosis. In an autopsy study, almost half of burned patients with candidemia had cerebral involvement. Therefore, a positive blood culture should prompt systemic antifungal therapy.

Staphylococcus aureus

S. aureus spreads to the brain by way of endocarditis in burned patients. Intracranial spread from other sites has been reported but rarely. The sequence of events is burn wound infection, bacteremia, infection of a heart valve, and embolism of infected material to the brain, with infarction or microabscess formation. Other cerebral complications of endocarditis, such as meningitis and mycotic aneurysm, probably occur in burned patients but have not been reported. Intracranial staphylococcal infections begin relatively late—in most cases more than 10 days after the burn—because the brain is infected after the burn wound and endocardium. The frequency of CNS infection with this organism has declined since the mid-1970s because better antibiotic treatment of burn wound infection prevents the development of endocarditis. The diagnosis of staphylococcal cerebral microabscesses is as hard as that of microabscesses due to Candida , but the identification of S. aureus as the cause is easier because blood cultures are positive. The diagnosis of a staphylococcal CNS infection should prompt a search for endocarditis.

Septic Infarction

Cerebral infarction is due more often to complications of the burn than atherosclerosis, atrial fibrillation, and other premorbid conditions unrelated to the burn. Each infection discussed earlier can cause septic occlusion of cerebral blood vessels, with infarction of brain. Meningeal infection can extend into the walls of arteries and veins that run through the subarachnoid space, and that may lead to inflammation and occlusion of affected vessels. This is a common complication of P. aeruginosa meningitis and can occur in the first week of disease. Embolism of infected material with occlusion of cerebral arteries is a classic complication of infective endocarditis. Invasive cerebral candidiasis causes mainly microabscesses; infarcts are fewer. Only one burned patient with cerebral aspergillosis has been reported, and it took the form of septic infarction, but Aspergillus is a common cause of systemic infection in patients with burns.

Radiologic features do not distinguish septic infarcts from those caused by premorbid vascular disease, but certain clinical points are helpful. Septic infarction may affect patients of any age and does not occur during the first week after a burn. Patients have extensive burns and systemic signs of sepsis. Focal neurologic deficits do not improve. In contrast, infarction caused by premorbid conditions may occur at any time during the hospital course and regardless of the severity of the burn or of the presence of systemic infection. Patients are usually elderly, have conventional risk factors for cerebral infarction, and may have had previous cerebral infarcts or coronary or peripheral vascular disease.

When a burned patient has a cerebral infarct and a septic cause seems likely, it is important to determine the mechanism involved—meningitis, endocarditis, or fungal invasion of a vessel—and the responsible microorganism. If the patient was neurologically normal before cerebral infarction, meningitis is unlikely. Physical signs of meningitis, infective endocarditis, or disseminated candidiasis may be found. The mechanism and etiology of septic infarcts correlate with one another. Cerebral infarction in a patient with S. aureus bacteremia suggests the presence of endocarditis. A systemic P. aeruginosa infection suggests that meningitis due to that organism underlies the infarct. If meningitis is found, it is the likely mechanism of infarction, and P. aeruginosa is the probable cause. Thus, examination of the CSF should always be considered in a burned patient who has had a cerebral infarct. If neither meningitis nor endocarditis is found, fungal invasion of cerebral blood vessels should be suspected. Cerebral infarction in a patient with invasive candidiasis or aspergillosis suggests that the infection has spread to the brain. A cerebral infarct in a patient with systemic signs of sepsis but negative cultures suggests the possibility of infection with Candida or Aspergillus.

Disseminated Intravascular Coagulation and other Causes of Cerebral Infarction

DIC is a well-known complication of deep, extensive burns. Fibrin thrombi occlude capillaries and small arteries and veins throughout the body. In the brain, disseminated hemorrhagic infarcts and microinfarcts are the result. They may or may not produce focal cerebral signs. DIC, like disseminated microabscesses, may simulate a metabolic or toxic encephalopathy. CT detects the larger infarcts, and micro-infarcts may appear on MRI. DIC is unlikely to be the cause of early neurologic symptoms; it usually begins later than the first week after a burn, and never before the fourth day. Heparin has not proved helpful in treating DIC in patients with burns. Treatment of the infection and hypotension causing DIC and replacement of depleted platelets and clotting factors are the recommended approaches.

Cerebral infarction in the arterial borderzone may occur early in the hospital course as a complication of burn shock and, later, with septic shock. The location of the infarct on brain imaging and the clinical setting suggest the diagnosis. Cerebral infarction caused by occlusion of dural sinuses and large and small cerebral veins has been reported in burned patients. Meningitis is not associated. DIC or intravascular volume depletion may be responsible. Magnetic resonance venography or routine MRI can detect occlusion of large venous channels. Nonbacterial thrombotic endocarditis and deep venous thrombosis with paradoxical cerebral embolism are possible, but unreported, causes of cerebral infarction in burned patients.

Intracranial Hemorrhage

Intracranial hemorrhage occurs much less often than cerebral infarction in burned patients. Lobar hemorrhage, subarachnoid hemorrhage, and widespread parenchymal petechiae (brain purpura) have been reported. A bleeding diathesis related to DIC or thrombocytopenia is the cause. Cerebral hematomas and infarcts may both be present in patients with DIC.