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Cerebral glucose metabolism is decreased in white matter changes in patients with phenylketonuria
S Hasselbalch1, G M Knudsen, P B Toft
1Department of Neurology, State University Hospital, Copenhagen, Denmark.
Abstract:
Cerebral magnetic resonance imaging (MRI) has revealed white matter changes in patients with phenylketonuria (PKU), an inborn error of metabolism with increased plasma phenylalanine level. Because the significance of these lesions is unknown, this study was undertaken to determine whether glucose metabolism was depressed in cerebral white matter MRI changes in patients with PKU. Four patients with PKU and nine healthy volunteers with an average age of 23 y (range 19-26 y) and 23 y (range 20-27 y), respectively, were studied. The IQ of patients with PKU was between 58 and 97. Cerebral MRI and positron emission tomography images with 18F-deoxyglucose were obtained, and arteriovenous differences for oxygen and glucose as well as cerebral blood flow was measured simultaneously to determine global cerebral oxygen and glucose metabolism. Cerebral MRI revealed that all patients with PKU had white matter changes with characteristic localization. In patients with PKU, regional glucose metabolism was 36% lower in the anterior periventricular areas, 0.14 +/- 0.06 compared with 0.22 +/- 0.04 mumol.g-1.min-1 in controls (mean +/- SD, p < 0.05, Mann-Whitney). Further, the ratio between glucose metabolism in the affected white matter and the cortex was 14% lower in the patients, decreasing from 0.57 +/- 0.05 to 0.48 +/- 0.06 (p < 0.05). Global cerebral blood flow, oxygen and glucose consumption were similar in the two groups. In conclusion, regional glucose metabolism is lower in MRI-demonstrated white matter changes. In mildly intellectually impaired patients with PKU, global cerebral glucose and oxygen metabolism remain intact.
Insights
Phenylketonuria (PKU) patients show reduced glucose metabolism in white matter lesions. Global brain metabolism remains normal, indicating localized metabolic changes in PKU patients with white matter abnormalities.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Medical Imaging
Background:
- Phenylketonuria (PKU) is an inborn error of metabolism characterized by elevated plasma phenylalanine levels.
- Cerebral magnetic resonance imaging (MRI) in PKU patients has identified white matter changes, but their functional significance remains unclear.
Purpose of the Study:
- To investigate whether glucose metabolism is reduced in cerebral white matter lesions observed in patients with PKU.
- To compare regional and global cerebral metabolism between PKU patients and healthy controls.
Main Methods:
- Utilized positron emission tomography (PET) with 18F-deoxyglucose alongside cerebral MRI.
- Measured arteriovenous differences for oxygen and glucose, and cerebral blood flow to assess global metabolism.
- Analyzed regional glucose metabolism in white matter and cortical areas.
Main Results:
- All PKU patients exhibited characteristic white matter changes on cerebral MRI.
- Regional glucose metabolism was significantly lower (36%) in the anterior periventricular white matter of PKU patients compared to controls.
- The ratio of glucose metabolism in affected white matter to the cortex was 14% lower in PKU patients.
- Global cerebral blood flow, oxygen, and glucose consumption were comparable between PKU patients and controls.
Conclusions:
- Regional glucose metabolism is depressed in MRI-identified white matter changes in PKU patients.
- Despite localized white matter metabolic alterations, global cerebral glucose and oxygen metabolism are preserved in mildly intellectually impaired PKU patients.