Brain Advance Access originally published online on October 22, 2007
Brain 2007 130(12):3102-3110; doi:10.1093/brain/awm165
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Association between cortical metabolite levels and clinical manifestations of migrainous aura: an MR-spectroscopy study
1Stroke Prevention Research Unit, University Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, 2MRC Biochemical and Clinical Magnetic Resonance Unit, Department of Biochemistry, University of Oxford, John Radcliffe Hospital, Headington,Oxford OX3 9DU and 3Department of Neurology, Northampton General Hospital NHS Trust, Cliftonville, Northampton NN1 5BD, UK
Correspondence to: Ursula Schulz, University Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK E-mail: ursula.schulz{at}doctors.net.uk
Previous studies suggest an abnormal cerebral cortical energy metabolism in migraineurs. If causally related to the pathophysiology of migraine, these abnormalities might show a dose–response relationship with the duration and severity of aura symptoms. While such a trend has been suggested in phosphorus spectroscopy (31P-MRS) studies, it has not been considered in proton spectroscopy (1H-MRS) studies and it has not been studied in cerebral white matter. We aimed to determine whether for any of the metabolites measured by 31P-MRS or 1H-MRS there was a dose-response relationship with aura duration and severity, and whether such an association was also present in cerebral white matter. We studied patients with migraine with aura and healthy controls with 31P-MRS and with 1H-MRS. We measured metabolite ratios in grey and in white matter and in the patients, we related metabolite levels to the clinical characteristics and duration of the aura. In patients, the phosphocreatine/phosphate (PCr/Pi) ratio decreased significantly with increasing aura duration and was significantly lower in patients with hemiplegic migraine than in patients with non-motor aura. Overall the metabolite ratios did not differ significantly between patients and controls, but compared with controls the PCr/Pi ratio in patients with hemiplegic migraine and in patients with persistent aura >7 days was significantly lower. These changes were only present in grey matter. Results for 1H-MRS did not differ significantly between patients and controls, and they showed no association with duration or severity of symptoms. In this study, metabolite ratios differed significantly between patients with different aura phenotypes and with increasing aura duration. In addition, only in some patient subgroups were metabolite ratios significantly different from controls. These findings support the concept that migraine with aura is a heterogeneous disorder with distinct pathophysiological subtypes. They further suggest that rather than determining the susceptibility to developing a migraine attack, changes in cortical energy metabolism may determine the clinical manifestations of the migrainous aura once an attack has started.
Key Words: MR-spectroscopy; migraine with aura; pathophysiology; migraine pathogenesis
Abbreviations: ATP, adenosine tri-phosphate; Cre, creatinine; Cho, choline; 1 DSI, one dimensional spectroscopic imaging; MRI, magnetic resonance imaging; NAA, N-acetyl aspartate; PCr/Pi, phosphocreatinine/phosphate; SNR, signal to noise ratio
Received March 8, 2007. Revised May 26, 2007. Accepted June 28, 2007.