CEREBRAL HERNIATION AND FATAL HYPERAMMONEMIA WITH NORMAL HEPATIC FUNCTION. R. Tripathi 1 , E. Warm 1 ; 1 University of Cincinnati, Cincinnati, OH LEARNING OBJECTIVES: 1) Determine differential diagnosis and treatment of severe hyperammonemia and microvesicular steatosis, 2) Describe the mechanism of action of a previously unreported enzyme deficiency (Hepatic Glutamine Synthetase Deficiency) that has fatal consequences, and 3) Discuss appropriate screening for this deficiency. CASE INFORMATION: A 60 year-old white male with a past medical history significant only for chronic obstructive lung disease was admitted to the hospital with shortness of breath and pneumonia. He was treated with piperacillin/tazobactam, steroids and inhalers. On day 2 of hospitalization, the patient developed mental status changes and had an ammonia level of 41. By day 3 he developed seizures, and on day 4 he was comatose with an ammonia level of 2808. At that point, family withdrew all support. Throughout his course, the patient had essentially normal liver enzymes. Autopsy showed pulmonary embolism with infarction, ischemic colitis, cerebellar tonsil herniation, and multifocal areas of microvesicular steatosis in less than 50% of liver. DISCUSSION: Microvesicular steatosis has a limited differential including Reye's syndrome and it is usually not associated with normal liver function enzymes and tremendous increases in ammonia. Similar histopathological and clinical findings as in our patient have been described in patients with heart-lung transplantation. A case series of these orthotopic lung transplant patients with fatal hyperammonemia have shown them to have a hepatic glutamine synthetase deficiency with normal urea cycle and liver function enzymes. The increased ammonia is shunted to the cerebrospinal fluid. Initial increase in ammonia is thought to be secondary to an increased protein load (i.e. gastrointestinal bleeds, TPN) and/or increased catabolic processes (i.e. major surgery). Patients with intact glutamine synthetase enzymes are able to handle this increased ammonia production and there is a pulmonary process in patients with the deficiency for clearing the excess ammonia. A combination of hepatic enzyme deficiency, increased protein load and acute pulmonary disease could be postulated to be the cause of rapid hyperammonemia, cerebral herniation and death in our patient. This is a recently reported entity that may have been underdiagnosed in the critical care setting in the past. In the future, screening for this disorder may be important before patients are candidates for heart-lung transplantation or other pulmonary surgery. It may be important currently to screen patients with mental status changes and no known liver disease with ammonia levels because the only proven treatment modality for severe hyperammonemia is emergent hemodialysis. LEARNING OBJECTIVES: Identify the causes of acute paralysis in the patient who uses drugs.Illustrate the importance of using the history and physical exam to quickly discern the correct diagnosis while definitive studies are pending CASE INFORMATION: A 20 year-old man presented with acute onset of bilateral lower extremity weakness and anesthesia shortly after arriving in New Orleans. He reported passing out for 12 hours after injecting heroin and cocaine. When he regained consciousness, he could not ambulate and had to pull himself to the telephone to call for help. On physical exam, he was afebrile with normal vital signs. He had no heart murmurs and there were no skin ulcerations. He had bilateral loss of sensation in the L4-S2 distribution. He was unable to dorsiflex, plantarflex, invert or evert his ankles. Patellar reflexes were normal; ankle reflexes were absent bilaterally. Flexion of the hips and knees, and sphincter tone were normal. The remaining neurologic exam was normal. The urinalysis showed large blood, but few red blood cells. His serum creatinine was 4.1 mg/dL and the creatinine kinase was 43,900 U/dL. All other laboratory values were normal. The patient was diagnosed with rhabdomyolysis and a compression neuropathy of the peroneal nerves. He received aggressive intravenous hydration; his creatinine decreased to 1.3mg/dL at discharge. He regained sensation and progressive motor function in his lower extremities. DISCUSSION: Acute paralysis is a medical emergency, which requires prompt diagnosis and treatment. The differential diagnosis in the intravenous drug user includes wound botulism, paradoxical embolism with stroke, HTLV-1 with spastic paraparesis, spinal cord compression from epidural abscess, nerve compression and rhabdomyolysis. The history and physical exam can quickly discern the correct diagnosis while definitive studies are pending. The abscence of skin wounds and cranial nerve deficits excluded botulism; the distribution of nerve deficits were inconsistent with a cerebral stroke and there was no murmur on cardiac exam. The time course for the paralysis was too rapid for HTLV-1 infection, and the normal sphincter tone and hip function argued against spinal cord compression. Deductive reasoning led to the diagnosis of nerve compression and rhabdomyolysis, which was confirmed by laboratory testing. Upon further questioning, the patient reported finding himself with his buttocks on the floor, his knees draped over the metal railing of the shower doors and his torso slumped over his lower extremities. This resulted in compression of the peroneal and tibial nerves proximal to the popliteal fossa with subsequent paralysis.