Purpose or Case Report: Magnetic Resonance Spectroscopy (MRS) is an important imaging adjunct for the diagnosis of hypoxic ischemic injury and brain death. As the concentration of adenosine triphosphate is depleted, the cell switches from oxidative phosphorylation to anaerobic glycolysis. The byproduct of this metabolic pathway is the creation of lactate from pyruvate. This leads to lactic acidosis, which can be detected with MRS. The presence of a lactate peak on MRS is not specific to the degree of hypoxic injury. In hypoxic conditions, other metabolites are detectable by MRS such as Alanine. Alanine is a product of the glucose-alanine cycle, where Pyruvate is converted to Alanine. We hypothesize the presence of high level of Alanine is seen only in severe hypoxia, and therefore may be a more specific marker for severe HIE and brain death.
Methods & Materials: This was a case controlled study where pediatric patients with the diagnosis of brain death, utilizing nuclear medicine Cerebral Blood Flow (CBF) studies as confirmatory studies; were compared to age matched controls from 1 tertiary referral institution from January 1 2000 through June 30 2021. Inclusion criteria were patients with CBF study and clinical diagnosis of brain death which had also undergone MRS within the prior week. Exclusion criteria were lack of concurrent confirmatory CBF study and lack of quantitative MRS data. Patients were age and sex matched with patients with normal MRS exams.
Results: Our study included 11 patients, age 5 months to 16 years. There were 7 males and 4 females. In the study group the mean Alanine concertation was 2.14 (mmol/L); standard deviation of 0.77. In the control group the mean alanine concentration was 0.06 (mmol/L); standard deviation of 0.02. Wilcoxon T yielded P value of 0.006, mean difference of 1.84 (mmol/L), with 95% CI 0.43-4.11.
Conclusions: There is a statistically significant increased concentration of alanine in patients with a diagnosis of brain death when compared with patients without brain death. This study was an appropriate first step in confirming the presence and specificity of an alanine peak in this patient population. This pilot study gives us enough data to move forward with a larger goal: stratifying the severity of HIE based on Alanine concentration. Future studies will expand the test group with additional cases provided by our child neurology colleagues.