Intracranial Pressure Monitoring Demonstrates that Cerebral Edema Is Not Correlated to Hyperammonemia in a Child with Ornithine Transcarbamylase Deficiency

Abstract

Background: Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea cycle resulting in increased plasma levels of ammonia and glutamine and cerebral edema. However, the underlying mechanism of brain cytotoxicity remains controversial. Our objective is to present an unusual acute hyperammonemic crisis suggesting a key role of brain glutamine to mediate ammonia neurotoxicity and the interest of intracerebral pressure (ICP) monitoring to maintain adequate cerebral perfusion pressure and to prevent neurological damages.

Patient: A 6-year-old boy with OTCD was admitted for an acute hyperammonemic encephalopathy following viral infection. At admission, he presented vomiting, confusion, lethargy (Glasgow scale 7/15), and bilateral papilledema, suggesting cerebral edema. Plasma ammonia level was slightly increased (194 μmol/L, rr 25–50 μmol/L), contrasting with the severity of neurological deterioration and with high levels of glutamine in plasma (1,949 μmol/L, rr 335–666 μmol/L) and the brain (10-fold increase on in vivo MR spectroscopy). The patient was placed on neuroprotective treatments and respiratory support.

Main Results: With a hypercaloric protein-free diet and nitrogen scavenger drugs, plasma levels of ammonia and glutamine rapidly decreased without neurological improvement. Continuous ICP monitoring showed repetitive peaks of pressure up to 60 mmHg in the first four days and was helpful to manage neuroprotective treatments. After several days, the patient progressively recovered without cognitive or motor disability.

Conclusion: This case report highlights the discrepancy between the severity of neurological impairment, presumably related to high level of brain glutamine, and plasma levels of ammonia or glutamine in a child with acute hyperammonemic encephalopathy related to OTCD. In this situation, continuous ICP monitoring was helpful to manage neuroprotective treatments and prevent brain damages.

Competing interests: None declared

Appendices

Conflicts of Interest

The authors declare no disclosure.

Take-Home Message

This case report highlights the key role of brain glutamine to mediate ammonia neurotoxicity in urea cycle disorders and the interest of monitoring intracranial pressure to maintain adequate cerebral perfusion pressure and to prevent neurological damages.

Compliance with Ethics Guidelines

All the authors declare no conflict of interest.

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

The following are the details of the contributions of individual authors: JC, GF, NF, NRR, TP, and ES for patient management in ICU; MT and FL for metabolic management; NT for surgical placement of intracranial pressure monitoring; and LB and BM for MRI analyses. JC and FL wrote the paper. All coauthors have read the manuscript and approved its submission to the JIMD Reports.