Progressive Decrease in N-Acetylaspartate/Creatine Ratio in a Teenager with Type 1 Diabetes and Repeated Episodes of Ketoacidosis without Clinically Apparent Cerebral Edema: Evidence for Permanent Brain Injury

Discussion

In this adolescent with type 1 DM, we observed a decrease in NAA/Cr ratios in the basal ganglia during each of 2 episodes of DKA. NAA/Cr ratios improved after recovery from each episode of DKA but did not return to baseline values. This pattern implies a component of permanent neuronal dysfunction or injury resulting from DKA.

NAA is a putative neuronal marker. Decreases in NAA may result from decreased neuronal viability or function, or neuronal loss. A previous study has demonstrated acute decreases in NAA levels in ischemic brain tissue, making NAA a valuable marker of brain injury.⁴ NAA levels have also been useful in predicting the degree of injury and potential recoverability of brain damage following head injury.⁴ Reduction of cerebral NAA may be reversible; thus, it can be used as a dynamic marker of neuronal dysfunction and integrity.⁵

The basal ganglia are a region thought to be particularly susceptible to injury caused by DKA-related cerebral edema.⁶ The vulnerability of the basal ganglia has been hypothesized to be related to the high adenosine triphosphate demand of this region.⁶ Some studies suggest that cerebral hypoperfusion may occur during DKA, resulting from dehydration and cerebral vasoconstriction related to hypocapnia.⁷ Hyperglycemia may also potentiate ischemic neuronal injury. The observed decrease in NAA/Cr during DKA correlates with these hypotheses and suggests that neuronal injury may result from DKA, even in the absence of clinically apparent cerebral edema or substantial mental status changes during DKA.

Previous studies by our group have documented consistently lower NAA/Cr values during DKA treatment compared with values measured after resolution of DKA.⁸ The increase in NAA/Cr after recovery from DKA implies a degree of neuronal recovery. In our previous studies, however, no comparison MR spectroscopy data were available before the DKA episodes; therefore, it was not possible to determine whether the recovery from DKA was complete. In the patient reported here, it appears that the neuronal recovery from DKA may not have been complete. The patient's NAA/Cr ratio after the second episode of DKA did not return to the baseline measurement obtained after his first DKA episode. It is, therefore, possible that repeated DKA episodes may result in progressive neurologic injury, which may lead to neurologic and/or cognitive decline in children with type 1 DM.

Supporting this possibility, a recent study found that a history of DKA was the strongest predictor of cognitive dysfunction in children with type 1 DM.³ Children with a history of DKA performed poorly on tests of contextual memory compared with children with type 1 diabetes who had never experienced DKA. Most children in the study had only experienced 1 DKA episode, typically at the time of diagnosis of diabetes. Differences in memory function between the 2 groups persisted after adjusting for age, duration of diabetes, episodes of hypoglycemia, and measures of glycemic control. Unfortunately, the patient reported here did not have neurocognitive testing performed, and the memory deficits reported in the study cited above are subtle and unlikely to be detectable without specific testing. Therefore, we cannot correlate the neuroimaging findings with cognitive data for this specific patient.

In summary, these data suggest that DKA may cause neuronal dysfunction or injury from which the patient recovers partially, but not completely. It is, therefore, possible that repeated DKA episodes may lead to progressive neurologic and/or cognitive decline in children with type 1 DM, and further study is warranted.