Cerebral sodium (23Na) magnetic resonance imaging in patients with migraine—a case-control study

DOI: https://doi.org/10.1007/s00330- 019- 06299- 1

Abstract-Summary Evaluation of MRI-derived cerebral 23Na concentrations in patients with migraine in comparison with healthy controls.

In this case-control study, 24 female migraine patients (mean age, 34 ± 11 years)

were enrolled after evaluation of standardized questionnaires.

The combined patient cohort was matched to 12 healthy female controls (mean

age, 34  ±  11 years).

23Na concentrations of all patients in the CSF were significantly higher than in

healthy controls (p < 0.001).

The CSF of both the migraine and mixed migraine/TTH group showed signifi- cantly increased sodium concentrations compared to the control group (p = 0.007 and p <  0.001).

Within the patient cohort, a positive correlation between pain level and TSC in

the CSF (r  = 0.62) could be observed.

MRI-derived cerebral 23Na concentrations in the CSF of migraine patients were

found to be statistically significantly higher than in healthy controls.

Case-control study shows significantly higher sodium concentrations in cerebro-

spinal fluid of migraineurs.

Cerebral sodium MRI may become a non-invasive imaging tool for drugs to modulate sodium, and hence migraine, on a molecular level, and influence patient management.

Extended: Future studies should consider scanning volunteers and patients at the

same time of day to exclude circadian rhythm changes [418].

This will hopefully help to reduce the burden of migraine in the future.

Introduction Another study by the same group revealed higher sodium concentrations in lumbar cerebrospinal fluid (CSF) of migraine patients, which was drawn during migraine [419].

For the treatment of headaches in general, it is important to distinguish between

migraine and TTH, since both forms are treated with totally different medications.

Many patients, especially those with frequent headaches, show symptoms of

both migraine and TTH.

3.4 Neuroimaging

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No in vivo imaging study in migraineurs or patients suffering from TTH measur-

ing sodium concentrations has been reported.

The purpose of our study was to evaluate MRI-derived cerebral 23Na concentra-

tions in patients with migraine in comparison with healthy controls.

We evaluated the impact of accompanying TTH on cerebral sodium concentra- tion, as well as potential influencing factors such as an accompanying aura, time between last attack and MRI measurement, disease duration, average duration and frequency of migraine attacks, pain intensity, and patients’ age.

Methods Migraine patients were recruited within our university hospital.

The survey includes a standardized checklist with 26 questions aiming at typical

migraine characteristics as well as TTH characteristics.

Migraine without TTH could be verified in 19 patients according to the case his- tory taken and survey guidelines, and 20 patients showed characteristics for both migraine and TTH.

TSCs of healthy controls and migraineurs overall, as well as compared to patients with migraine alone versus mixed migraine/TTH, were tested for differences using the Wilcoxon rank sum test.

Within the migraine cohort (migraine and mixed migraine/TTH), correlations between TSC in the different anatomic regions and migraine characteristics includ- ing onset of disease, length, historical typical intensity (scale 1–10) and frequency of attacks, and accompanying aura were tested using Pearson’s correlation for con- tinuous variables and the Kendall Tau test for ordinal variables.

Results No statistically significant age difference was observed between migraineurs and healthy volunteers (p  =  0.76) and migraineurs, mixed migraineurs/TTH patients, and volunteers (p = 0.9).

No statistically significant difference was found in the other anatomical areas (p

0.05 for WM, GM, brainstem, and cerebellum).

No significant differences between TSC of migraine patients with (n = 10) and without (n  =  14) an accompanying aura were found (p  >  0.05 for all anatomic regions).

No significant correlations were observed between the onsets of disease, length of migraine attacks, number of migraine attacks in the past 3  months, and age (p > 0.05 for all anatomic regions).

Analysis of age correlation with the different anatomic regions revealed no sta-

tistically significant results.

Discussion In this first human in vivo sodium imaging study in migraine, our data suggest sig- nificantly higher sodium concentrations in CSF of migraine patients compared with healthy controls, results that concur with the aforementioned results of increased lumbar CSF in migraine patients.

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3 Diagnosis

Breaking down the cohort into migraine and mixed migraine/TTH patients, the significantly increased values for TSC in CSF holds true for both groups compared with those of healthy controls.

Future studies including more patients suffering from chronic headaches will be

of interest to explore the consistency of this CSF sodium change in migraine.

Fifth, although manual ROI placement was done in a similar fashion and the same anatomic region for all volunteers and patients, a (semi-) automatic quantifica- tion tool would be preferable, as sodium concentrations may fluctuate according to a study by Abad et al. [420].

Conclusion We have tested the hypothesis that migraineurs might suffer from increased concen- trations of brain sodium and found significantly higher values in the CSF of migraine patients compared with healthy controls.

These observations provide further support for a role of brain sodium in the

pathophysiology of migraine.

If further in-depth studies can confirm our findings, cerebral 23Na MRI may aid in the pathophysiological understanding of migraine and may become a non- invasive imaging tool for drugs to modulate sodium, and hence migraine, on a molecular level.

Acknowledgement A machine generated summary based on the work of Meyer, Melissa M.; Schmidt, Alexander; Benrath, Justus; Konstandin, Simon; Pilz, Lothar R.; Harrington, Michael G.; Budjan, Johannes; Meyer, Mathias; Schad, Lothar R.; Schoenberg, Stefan O.; Haneder, Stefan. 2019 in European Radiology.

A volumetric magnetic resonance imaging study in migraine