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



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

Materials and methods

In this case-control study, 24 female migraine patients (mean age, 34 ± 11 years) were enrolled after evaluation of standardized questionnaires. Half (n = 12) of the cohort suffered from migraine, the other half was impaired by both migraine and tension-type headaches (TTH). The combined patient cohort was matched to 12 healthy female controls (mean age, 34 ± 11 years). All participants underwent a cerebral 23Na-magnetic resonance imaging examination at 3.0 T, which included a T1w MP-RAGE sequence and a 3D density-adapted, radial gradient echo sequence for 23Na imaging. Circular regions of interests were placed in predetermined anatomic regions: cerebrospinal fluid (CSF), gray and white matter, brain stem, and cerebellum. External 23Na reference phantoms were used to calculate the total 23Na tissue concentrations. Pearson’s correlation, Kendall Tau, and Wilcoxon rank sum test were used for statistical analysis.


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 significantly 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.

Key Points

• Cerebral sodium MRI supports the theory of ionic imbalances and may aid in the challenging pathophysiologic understanding of migraine.

• Case-control study shows significantly higher sodium concentrations in cerebrospinal 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.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6



Cerebrospinal fluid


Diffusion-weighted imaging


Fluid-attenuated inversion recovery


Gray matter


Magnetization-prepared rapid acquisition gradient echo


Magnetic resonance imaging


Standard deviation


Total sodium concentration


Tension-type headaches


White matter


  1. 1.

    Charles A (2010) Does cortical spreading depression initiate a migraine attack? Maybe not. Headache 50(4):731–733

    Article  Google Scholar 

  2. 2.

    Zhang X, Levy D, Noseda R, Kainz V, Jakubowski M, Burstein R (2010) Activation of meningeal nociceptors by cortical spreading depression: implications for migraine with aura. J Neurosci 30(26):8807–8814

    CAS  Article  Google Scholar 

  3. 3.

    Buzzi MG, Moskowitz MA (1992) The trigemino-vascular system and migraine. Pathol Biol (Paris) 40(4):313–317

    CAS  Google Scholar 

  4. 4.

    Sun YG, Pita-Almenar JD, Wu CS et al (2013) Biphasic cholinergic synaptic transmission controls action potential activity in thalamic reticular nucleus neurons. J Neurosci 33(5):2048–2059

    CAS  Article  Google Scholar 

  5. 5.

    Harrington MG, Chekmenev EY, Schepkin V, Fonteh AN, Arakaki X (2011) Sodium MRI in a rat migraine model and a NEURON simulation study support a role for sodium in migraine. Cephalalgia 31(12):1254–1265

    Article  Google Scholar 

  6. 6.

    Harrington MG, Fonteh AN, Cowan RP et al (2006) Cerebrospinal fluid sodium increases in migraine. Headache 46(7):1128–1135

    Article  Google Scholar 

  7. 7.

    Fernández-de-las-Peñas C, Madeleine P, Caminero AB, Cuadrado ML, Arendt-Nielsen L, Pareja JA (2010) Generalized neck-shoulder hyperalgesia in chronic tension-type headache and unilateral migraine assessed by pressure pain sensitivity topographical maps of the trapezius muscle. Cephalalgia 30(1):77–86

  8. 8.

    Bendtsen L (2000) Central sensitization in tension-type headache--possible pathophysiological mechanisms. Cephalalgia 20(5):486–508

    CAS  Article  Google Scholar 

  9. 9.

    Jensen R (1999) Pathophysiological mechanisms of tension-type headache: a review of epidemiological and experimental studies. Cephalalgia 19(6):602–621

    CAS  Article  Google Scholar 

  10. 10.

    Wetterling F, Chatzikonstantinou E, Tritschler L (2016) Investigating potentially salvageable penumbra tissue in an in vivo model of transient ischemic stroke using sodium, diffusion, and perfusion magnetic resonance imaging. BMC Neurosci 17(1):82

  11. 11.

    Zaaraoui W, Konstandin S, Audoin B (2012) Distribution of brain sodium accumulation correlates with disability in multiple sclerosis: a cross-sectional 23Na MR imaging study. Radiology 264(3):859–867

    Article  Google Scholar 

  12. 12.

    Petracca M, Fleysher L, Oesingmann N, Inglese M (2016) Sodium MRI of multiple sclerosis. NMR Biomed 29(2):153–161

    Article  Google Scholar 

  13. 13.

    Ouwerkerk R, Bleich KB, Gillen JS, Pomper MG, Bottomley PA (2003) Tissue sodium concentration in human brain tumors as measured with 23Na MR imaging. Radiology 227(2):529–537

    Article  Google Scholar 

  14. 14.

    Göbel H (2001) Classification of headaches. Cephalalgia 21(7):770–773

    Article  Google Scholar 

  15. 15.

    Konstandin S, Nagel AM (2014) Measurement techniques for magnetic resonance imaging of fast relaxing nuclei. MAGMA 27(1):5–19

    CAS  Article  Google Scholar 

  16. 16.

    Haneder S, Konstandin S, Morelli JN (2011) Quantitative and qualitative (23)Na MR imaging of the human kidneys at 3 T: before and after a water load. Radiology 260(3):857–865

    Article  Google Scholar 

  17. 17.

    Pogoda JM, Gross NB, Arakaki X (2016) Severe headache or migraine history is inversely correlated with dietary sodium intake: NHANES 1999-2004. Headache 56(4):688–698

    Article  Google Scholar 

  18. 18.

    Harrington MG, Salomon RM, Pogoda JM (2010) Cerebrospinal fluid sodium rhythms. Cerebrospinal Fluid Res 7:3

  19. 19.

    Hodgkin AL, Katz B (1949) The effect of sodium ions on the electrical activity of giant axon of the squid. J Physiol 108(1):37–77

    CAS  Article  Google Scholar 

  20. 20.

    Arakaki X, Foster H, Su L (2011) Extracellular sodium modulates the excitability of cultured hippocampal pyramidal cells. Brain Res 1401:85–94

    CAS  Article  Google Scholar 

  21. 21.

    Zakharov A, Vitale C, Kilinc E (2015) Hunting for origins of migraine pain: cluster analysis of spontaneous and capsaicin-induced firing in meningeal trigeminal nerve fibers. Front Cell Neurosci 9:287

  22. 22.

    Madelin G, Regatte RR (2013) Biomedical applications of sodium MRI in vivo. J Magn Reson Imaging 38(3):511–529

    Article  Google Scholar 

  23. 23.

    Thulborn K, Lui E, Guntin J (2016) Quantitative sodium MRI of the human brain at 9.4 T provides assessment of tissue sodium concentration and cell volume fraction during normal aging. NMR Biomed 29(2):137–143

    Article  Google Scholar 

  24. 24.

    Mirkes CC, Hoffmann J, Shajan G, Pohmann R, Scheffler K (2015) High-resolution quantitative sodium imaging at 9.4 Tesla. Magn Reson Med 73(1):342–351

    Article  Google Scholar 

  25. 25.

    Abad N, Rosenberg JT, Hike DC, Harrington MG, Grant SC (2018) Dynamic sodium imaging at ultra-high field reveals progression in a preclinical migraine model. Pain 159(10):2058–2065

    CAS  Article  Google Scholar 

Download references


IRB approval: Medical Ethics Committee II Mannheim, Germany; reference number: 2013 566N – MA.


The authors state that this work has not received any funding.

Author information



Corresponding author

Correspondence to Melissa M. Meyer.

Ethics declarations


The scientific guarantor of this publication is Melissa Meyer, MD.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise.

Lothar R. Pilz, co-author.

Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.


• prospective

• case-control study

• performed at one institution

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Meyer, M.M., Schmidt, A., Benrath, J. et al. Cerebral sodium (23Na) magnetic resonance imaging in patients with migraine — a case-control study. Eur Radiol 29, 7055–7062 (2019). https://doi.org/10.1007/s00330-019-06299-1

Download citation


  • Sodium
  • Magnetic resonance imaging
  • Migraine
  • Cerebrospinal fluid