Brain biochemistry in Duchenne muscular dystrophy: a 1H magnetic resonance and neuropsychological study.
Duchenne muscular dystrophy (DMD) is a progressive muscle disorder associated with an intellectual deficit which is non-progressive. We obtained localised 1H magnetic resonance spectra from the left frontal lobe and left cerebellum of 15 boys with DMD (mean age 106 months+/-32) and 15 similarly aged control boys (mean age 115 months+/-31); all boys underwent a battery of neuropsychological tests. We found a significant (P<0.01) increase in the ratio of choline-containing compounds to N-acetylaspartate (Cho/NA) in the left cerebellum in boys with DMD compared with control boys. There was no change in the creatine/NA ratio and a significant increase (P=0.03) in the Cho/creatine ratio, suggesting that the change in Cho/NA ratio was due to an increase in choline-containing compounds; this increase has been previously observed in the brain of the murine model of DMD, the mdx mouse. No significant changes were observed in spectra obtained from left frontal lobe in DMD compared to controls. We also observed a significant association between Cho/NA in the left cerebellum, and the performance of DMD boys on the Matrix Analogies Test (MAT). The MAT is a test of visuo-spatial ability and non-verbal reasoning which requires neither manual dexterity nor a verbal response for an adequate performance. A comparison of DMD boys whose cerebellar Cho/NA fell within 2 standard deviations of the control norm (0.56+/-0.24) with DMD boys whose cerebellar Cho/NA was outside this range (i.e. >0.80) revealed a significant difference in ability on the MAT (P<0.05). DMD boys whose Cho/NA ratio is more than two standard deviations higher than controls perform significantly better on the MAT than DMD boys whose Cho/NA ratio is within the normal range. This finding suggests that the observed elevation in Cho/NA and Cho/creatine is not associated with intellectual deficit (as sampled by the MAT), and may represent a compensatory mechanism. The possible interpretations of these metabolic changes are discussed.
Rae
C
C
MRC Biochemical and Clinical Magnetic Resonance Spectroscopy Unit, John Radcliffe Hospital, Headington, Oxford, UK. crae@biochem.usyd.edu.au
Scott
R B
RB
Thompson
C H
CH
Dixon
R M
RM
Dumughn
I
I
Kemp
G J
GJ
Male
A
A
Pike
M
M
Styles
P
P
Radda
G K
GK
D000367:Age Factors; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D002648:Child; D002794:Choline / Q000378:metabolism; D003071:Cognition; D003401:Creatine / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009136:Muscular Dystrophies / Q000378:metabolism* / Q000523:psychology*; D009483:Neuropsychological Tests
D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline