Most patients are children, boys and girls being equally affected, but rare instances are known in infants (Huttenlocher and Trauner) and young adults. In most cases, the encephalopathy is preceded for several days to a week by fever, symptoms of upper respiratory infection, and protracted vomiting. These are followed by the rapid evolution of stupor and coma, associated in many cases with focal and generalized seizures, signs of sympathetic overactivity (tachypnea, tachycardia, mydriasis), decorticate and decerebrate rigidity, and loss of pupillary, corneal, and vestibuloocular reflexes. One or two such cases were included in the series of acute “toxic encephalopathy” reported by Lyon and colleagues (see “Acute Toxic Encephalopathy” in Chap. 31). In infants, respiratory distress, tachypnea, and apnea are the most prominent features.
The liver may be greatly enlarged, often extending to the pelvis and providing an important diagnostic clue as to the cause of the cerebral changes. Initially there is a metabolic acidosis, followed by a respiratory alkalosis (rising arterial pH and falling Pco2). The CSF is usually under increased pressure and is acellular; glucose values may be low, reflecting the hypoglycemia. The serum ALT, coagulation times, and blood ammonia are increased, sometimes to an extreme degree. The EEG is characterized by diffuse arrhythmic delta activity, progressing to electrocerebral silence in patients who fail to survive. CT and MRI show the cerebral swelling but are difficult to interpret in these young individuals, who lack any adult brain atrophy.
The major pathologic findings are cerebral edema, often with cerebellar herniation, and infiltration of hepatocytes with fine droplets of fat (mainly triglycerides); the renal tubules, myocardium, skeletal muscles, pancreas, and spleen are infiltrated to a lesser extent. There are no inflammatory lesions in the brain, liver, or other organs. There is not full agreement as to the pathogenesis of this disorder and the mechanism of aspirin toxicity but mitochondrial dysfunction has been implicated.
In a series of children with blood ammonia levels greater than 500 mg/dL who were treated during the years 1967 to 1974, Shaywitz and colleagues reported a mortality of 60 percent. Once the child became comatose, death was almost inevitable. In more recent years, early diagnosis and initiation of treatment before the onset of coma have reduced the fatality rate to 5 to 10 percent. Treatment consists of the following measures: temperature control with a cooling blanket; nasotracheal intubation and controlled ventilation to maintain Pco2 below 32 mm Hg; intravenous glucose covered by insulin to maintain blood glucose at 150 to 200 mg/dL; administration of lactulose, neomycin enemas, and hemodialysis to directly lower the NH3 concentration; control of intracranial pressure by means of continual monitoring and the use of hypertonic solutions (see Chap. 30); and the maintenance of fluid and electrolyte balance (Trauner). Upon recovery, cerebral function returns to normal unless there had been deep and prolonged coma or protracted elevation of intracranial pressure.