Association between cortical metabolite levels and clinical manifestations of migrainous aura: an MR-spectroscopy study.

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.

[1]  J. Olesen The International Classification of Headache Disorders , 2008, Headache.

[2]  M. Kirchmann Migraine with aura: new understanding from clinical epidemiologic studies , 2006, Current opinion in neurology.

[3]  J. Olesen,et al.  Implications of Clinical Subtypes of Migraine With Aura , 2006, Headache.

[4]  T. Strom,et al.  Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine , 2005, The Lancet.

[5]  M Wilke,et al.  1H-MRS alterations in the cerebellum of patients with familial hemiplegic migraine type 1 , 2005, Neurology.

[6]  Andrea Alberti,et al.  Functional 1H-MRS findings in migraine patients with and without aura assessed interictally , 2005, NeuroImage.

[7]  R. Swartz,et al.  Migraine is associated with magnetic resonance imaging white matter abnormalities: a meta-analysis. , 2004, Archives of neurology.

[8]  U. Reuter,et al.  Migraine aura: new information on underlying mechanisms , 2004, Current opinion in neurology.

[9]  Peter J. Goadsby,et al.  A Report on the Journal 2004 , 2004 .

[10]  F. Pierelli,et al.  Cerebellar metabolite alterations detected in vivo by proton MR spectroscopy. , 2003, Magnetic resonance imaging.

[11]  J. Olesen,et al.  Evidence for a separate type of migraine with aura , 2003, Neurology.

[12]  A. Ballabio,et al.  Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2 , 2003, Nature Genetics.

[13]  K. Welch,et al.  Contrasts in cortical magnesium, phospholipid and energy metabolism between migraine syndromes , 2002, Neurology.

[14]  B. Barbiroli,et al.  Deficient energy metabolism is associated with low free magnesium in the brains of patients with migraine and cluster headache , 2001, Brain Research Bulletin.

[15]  A. Blamire,et al.  Evidence for cellular damage in normal-appearing white matter correlates with injury severity in patients following traumatic brain injury: A magnetic resonance spectroscopy study. , 2000, Brain : a journal of neurology.

[16]  J. Clark,et al.  N-Acetyl Aspartate: A Marker for Neuronal Loss or Mitochondrial Dysfunction , 1998, Developmental Neuroscience.

[17]  Vanhamme,et al.  Improved method for accurate and efficient quantification of MRS data with use of prior knowledge , 1997, Journal of magnetic resonance.

[18]  Dennis E Bulman,et al.  Familial Hemiplegic Migraine and Episodic Ataxia Type-2 Are Caused by Mutations in the Ca2+ Channel Gene CACNL1A4 , 1996, Cell.

[19]  T. Yuasa,et al.  Elevation of cerebral lactate detected by localized sup 1 H-magnetic resonance spectroscopy in migraine during the interictal period , 1996, Neurology.

[20]  P. Montagna Magnetic Resonance Spectroscopy in Migraine , 1995, Cephalalgia : an international journal of headache.

[21]  P. Zaniol,et al.  Abnormal brain and muscle energy metabolism shown by 31P-MRS in familial hemiplegic migraine , 1995, Journal of the Neurological Sciences.

[22]  P. Zaniol,et al.  Abnormal brain and muscle energy metabolism shown by 31P magnetic resonance spectroscopy in patients affected by migraine with aura , 1992, Neurology.

[23]  N. Ramadan,et al.  The concept of migraine as a state of central neuronal hyperexcitability. , 1990, Neurologic clinics.

[24]  S. Levine,et al.  Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 31 NMR spectroscopy , 1989, Neurology.

[25]  P. Bottomley Spatial Localization in NMR Spectroscopy in Vivo , 1987, Annals of the New York Academy of Sciences.

[26]  D Matthaei,et al.  1H NMR chemical shift selective (CHESS) imaging. , 1985, Physics in medicine and biology.

[27]  R. B. Moon,et al.  Determination of intracellular pH by 31P magnetic resonance. , 1973, The Journal of biological chemistry.

[28]  P. Milner Note on a possible correspondence between the scotomas of migraine and spreading depression of Leão. , 1958, Electroencephalography and clinical neurophysiology.

[29]  A. A. Leão,et al.  SPREADING DEPRESSION OF ACTIVITY IN THE CEREBRAL CORTEX , 1944 .

[30]  J. Winn,et al.  Brain , 1878, The Lancet.

[31]  P. Goadsby,et al.  Recent advances in understanding migraine mechanisms, molecules and therapeutics. , 2007, Trends in molecular medicine.

[32]  O. Masaki,et al.  Elevation of cerebral lactate detected by localized ^1H-magneticresonance spectroscopy in migraine during the interictal period , 1996 .