Hyperammonemic Encephalopathy After Induction Chemotherapy for Acute Lymphoblastic Leukemia

Abstract

The syndrome of hyperammonemic encephalopathy occurs in patients who have received high-dose cytoreductive therapy for the treatment of hematologic malignancy. It is characterized by acute alteration in mental status and respiratory alkalosis associated with markedly elevated plasma ammonium levels in the absence of any identifiable cause and frequently results in cerebral edema, coma, and eventually death. Although the etiology of this syndrome is yet to be determined, it seems to be invariably multifactorial in nature. Optimal therapy remains elusive, and the critical step is increased awareness of the syndrome by measurement of plasma ammonia levels in patients with neurologic symptoms, leading to accurate diagnosis and the rapid implementation of therapy.

The toxicity of very prolonged courses of PEGasparaginase or Erwinia asparaginase in relation to asparaginase activity, with a special focus on dyslipidemia

“…6 It has been suggested in case reports that ammonia release could lead to encephalopathy. [13][14][15] Our prospective study, however, shows that ammonia level was not related to central neurotoxicity. Even the patients with hyperammonemia grade 3/4 did not experience central neurotoxicity and the four patients with central neurotoxicity grade 3/4 did not have higher ammonia levels than those without central neurotoxicity.…”

Hyperammonemia in review: pathophysiology, diagnosis, and treatment

“…The pathogenic mechanism is thought to be related to an acquired deficiency of glutamine synthetase of unknown cause. [60][61][62][63][64][65] Miscellaneous causes of hyperammonemia Hypoglycin (Jamaican vomiting sickness) This is caused by a toxin present in the unripe ackee fruit. The Jamaican vomiting sickness, which has a high mortality rate (up to 50%), is characterized by vomiting, lethargy, hallucinations, coma, hypoglycemia, hyperammonemia, and abnormal liver enzymes, which occur when this unripe fruit is ingested [6].…”

Differentiating hypersensitivity versus infusion-related reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia

“…[82] Asparaginase therapy has also been associated with nonantibody-mediated infusion reactions that may result from spikes in serum ammonia levels. [83][84][85][86] Ammonia accumulation occurs as asparaginase facilitates the rapid conversion of asparagine and glutamine to aspartic acid and glutamic acid, with ammonia as the shared by-product of both reactions. [10] Symptoms of hyperammonemia are often transient in nature and can include nausea, vomiting, headache, dizziness, and rash.…”