A 5-year-old, previously healthy, girl is brought to the emergency department due to lethargy and altered mental status. The patient was in her usual state of health until 5 days ago, when she developed a fever, malaise, headache, cough, and nasal discharge. The fever resolved with over-the-counter medications, and the patient was feeling better until this morning, when she developed nausea, vomiting, and lethargy. She has no chronic medical conditions and takes no prescription medications. Temperature is 36.8 C (98.2 F), blood pressure is 98/60 mm Hg, pulse is 110/min, and respirations are 20/min. The patient is not oriented to person, place, or time. Cardiopulmonary examination shows no abnormalities. Hepatomegaly is present; there is no splenomegaly. CT scan of the head reveals diffuse cerebral edema. Which of the following is the most likely cause of this patient's imaging findings?
Toxic-metabolic encephalopathy* & cerebral edema | |
Diagnosis | Precipitating factors |
Hypoxic-ischemic |
|
Diabetic ketoacidosis |
|
Hyponatremia |
|
Liver failure |
|
Reye syndrome |
|
*Acute cerebral dysfunction/mental status changes in the absence of primary CNS pathology. SIADH = syndrome of inappropriate antidiuretic hormone secretion. | |
This patient has acutely altered mental status and cerebral edema on CT scan, findings concerning for toxic-metabolic encephalopathy. The potential underlying etiologies are vast and are characterized by brain dysfunction in the absence of primary CNS disease (eg, infection, tumor). In this case, the patient's recent upper respiratory infection treated with over-the-counter medications, hepatomegaly, and rapid progression make Reye syndrome most likely.
Reye syndrome is a rare but potentially fatal condition that occurs in children who were given salicylates (eg, aspirin) for a viral illness (eg, influenza, varicella). The pathophysiology likely involves mitochondrial dysfunction from aspirin, which leads to impaired fatty acid metabolism and acute hepatic steatosis, as seen by this patient's hepatomegaly. With declining liver function, excess ammonia (ie, neurotoxin) accumulates and causes cerebral edema and encephalopathy (ie, altered mental status). Initial symptoms of increased intracranial pressure (ie, vomiting, lethargy) can rapidly progress to seizures, coma, and death.
Liver biopsy showing microvesicular steatosis in the context of acute toxic-metabolic encephalopathy is consistent with Reye syndrome but is not required for the diagnosis. Treatment is supportive, and parents should be reminded that aspirin is contraindicated in children except in the management of Kawasaki disease and rheumatologic diseases (eg, juvenile idiopathic arthritis).
(Choice A) Adrenal crisis can be precipitated by infection and cause hypotension, vomiting, and acute mental status changes. However, cerebral dysfunction is due to poor perfusion, not cerebral edema, from lack of cortisol. This patient's hepatomegaly, cerebral edema, and normal blood pressure make adrenal insufficiency unlikely.
(Choice C) Hypoglycemia, which can cause confusion and lethargy, may occur in Reye syndrome from decreased hepatic production of glucose but does not cause cerebral edema. Cerebral edema can be caused by hyperglycemia (eg, diabetic ketoacidosis), but this metabolic derangement is not seen in Reye syndrome.
(Choice D) Severe hypothyroidism (myxedema coma) can present with lethargy and disorientation, but hypothermia and bradycardia would also be present. In addition, hypothyroidism does not cause hepatomegaly or cerebral edema.
(Choice E) Urea is a neurotoxin that, in excess (eg, renal failure), can cause altered mental status (ie, uremic encephalopathy) but not cerebral edema. Signs of renal impairment (eg, hypertension, peripheral edema), not hepatomegaly, would be expected.
Educational objective:
Reye syndrome is a rare toxic-metabolic encephalopathy in children who have taken aspirin for a viral illness. Liver failure (microvesicular hepatic steatosis) leads to hyperammonemia, cerebral edema, and encephalopathy (ie, altered mental status).