Magnetic resonance spectroscopy in migraine: What have we learned so far?

Abstract

Objective: To summarize and evaluate proton (1H) and phosphorus (31P) magnetic resonance spectroscopy (MRS) findings in migraine. Methods: A thorough review of 1H and/or 31P-MRS studies in any form of migraine published up to September 2011. Results: Some findings were consistent in all studies, such as a lack of ictal/interictal brain pH change and a disturbed energy metabolism, the latter of which is reflected in a drop in phosphocreatine content, both in the resting brain and in muscle following exercise. In a recent interictal study ATP was found to be significantly decreased in the occipital lobe of migraine with aura patients, reinforcing the concept of a mitochondrial component to the migraine threshold, at least in a subgroup of patients. In several studies a correlation between the extent of the energy disturbance and the clinical phenotype severity was apparent. Less consistent but still congruent with a disturbed energy metabolism is an observed lactate increase in the occipital cortex of several migraine subtypes (MwA, migraine with prolonged aura). No increases in brain glutamate levels were found. Conclusion: The combined abnormalities found in MRS studies imply a mitochondrial component in migraine neurobiology. This could be due to a primary mitochondrial dysfunction or be secondary to, for example, alterations in brain excitability. The extent of variation in the data can be attributed to both the variable clinical inclusion criteria used and the variation in applied methodology. Therefore it is necessary to continue to optimize MRS methodology to gain further insights, especially concerning lactate and glutamate.

31P‐MRS in Migraine: Fallen Through the Cracks

“…In a retrospective study on patients with subacute daily headache (1-4 weeks durations), we observed that patients with a prior history of febrile illness are more likely to have neck pain and signs of meningismus (in addition to headache). 4 Our observation, 4 Almazov and Brand's observation, 2 and a few other observations 5 suggest a possibility of postinfectious pathology (most likely immunological) in meninges in patients who have a prior history of infections before the onset of headache. We further suggest that the interrelation between meninges and infections may be like the interrelation of synovial membrane to various viral infections for the development of reactive arthritis, as synovial membranes and meninges are of same type of tissue (membranous connective tissue).…”

“…2 Lakhan et al have selected only 2 studies, both using the 1 H-MRS technique in migraine with aura, and summarize interictal MRS findings in migraine as "a decreased N-acetylaspartate signal and a slight increase in lactate peak" but there is no mentioning of 31 P-MRS data at all. This came as a surprise as:…”

A splice variant in the ACSL5 gene relates migraine with fatty acid activation in mitochondria

“…The hypothesis of the mitochondrial component in migraine neurobiology has been supported in several studies, 32, 33, 34, 35, 36, 37 suggesting that an impairment of the mitochondrial oxidative metabolism, which ultimately causes energy failure in neurons and astrocytes, triggers migraine mechanisms. Furthermore, different types of assays performed in migraine sufferers have shown a decreased activity of the respiratory chain enzymes 33 and a correlation between the extent of the energy disturbance (low ATP levels), and the clinical phenotype severity.…”

ASICs as therapeutic targets for migraine

“…Assays focused on measuring changes in pH have traditionally been performed in humans by collecting plasma, CSF, or using magnetic-resonance spectroscopy or they could also be inferred from other markers e.g. lactate levels [142–144]. But these may not be sensitive enough to detect the small, and potentially local changes in pH that are necessary to activate ASICs.…”