Reye Syndrome



Reye Syndrome


Penelope Terhune Louis



Reye syndrome, first described in 1963, is an acute, life-threatening, postinfectious, metabolic encephalopathy that affects predominantly school-aged children, occasionally infants, and rarely adults. Over the years, the disease and its clinical manifestations have received widespread recognition.

Characteristically, a prodromal illness, most often influenza or varicella infection, is followed in 3 to 5 days by the onset of persistent and intractable vomiting. Initially, patients are well oriented but irritable and lethargic. Some patients have no change in consciousness and remain only lethargic, with no progression to unconsciousness. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are 3 to 30 times normal. The serum bilirubin level rarely exceeds 1 mg/dL. Serum ammonia concentrations are variable at presentation. As the encephalopathy worsens to a hyperexcitable state, the patient is intermittently out of contact with the environment. Further progression to a deeper comatose state is characterized by decerebrate and decorticate posturing, hyperventilation, and, finally, flaccid paralysis with loss of involuntary ventilatory control. The comatose patient uniformly has an elevated ammonia concentration ranging from 3 to 20 times normal. The encephalopathy typically persists for 24 to 96 hours, with gradual improvement occurring in survivors. Recovery of consciousness in patients with permanent neurologic impairment may require weeks.

Criteria for the case definition of Reye syndrome include the following: an acute, noninflammatory encephalopathy documented clinically by an alteration in consciousness and, if available, cerebrospinal fluid containing fewer than eight leukocytes per microliter; hepatopathy documented by liver biopsy on autopsy or a threefold or greater increase in the ALT, AST, or serum ammonia level; and no more reasonable explanation for the cerebral or hepatic abnormalities.

Accurately assessing the severity of the illness is important because the therapies for severely affected children are aggressive, invasive, and dangerous. Several staging systems have been developed, culminating in the National Institutes of Health Staging System (Box 405.1). The peak incidence of this disorder occurred in the 1960s and 1970s, and only rare cases have been reported since 1985.


PATHOGENESIS

Despite intensive study, the pathogenesis of Reye syndrome remains incompletely defined. Whether the pathogenesis can be explained by a primary injury to the mitochondria of multiple organs, including the brain, liver, and muscle, with its metabolic consequences, or by a primary hepatic injury that leads to metabolic consequences producing the biochemical abnormalities and encephalopathy remains unclear. Morphologic and biochemical studies have confirmed the presence of a characteristic injury. Pleomorphic, enlarged mitochondria with disrupted cristae, electron-lucent matrices, and reduced numbers of dense bodies are characteristic of the hepatic pathologic features of Reye syndrome. Associated reductions in mitochondrial enzymes involved in ureagenesis and gluconeogenesis and in enzymes associated with the citric acid cycle have been observed. Further evidence of mitochondrial injury is suggested by the finding of dicarboxylic acids in the urine and serum.

Morphologic and biochemical studies of the brain in patients with Reye syndrome have revealed swollen astrocytes and myelin blebs. Alterations in the morphologic features of the mitochondria have been identified only in neurons. Despite these morphologic changes, mitochondrial enzyme activities in the brain are not reduced as they are in the liver. This finding is somewhat surprising because it suggests that brain mitochondrial injury may play an unimportant role in the observed encephalopathy of Reye syndrome.

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Jul 24, 2016 | Posted by in ORTHOPEDIC | Comments Off on Reye Syndrome
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