Diffusion tensor imaging in middle-aged headache sufferers in the general population: a cross-sectional population-based imaging study in the Nord-Trøndelag health study (HUNT-MRI)

DOI: https://doi.org/10.1186/s10194- 019- 1028- 6

Abstract-Summary Several studies have investigated white matter with diffusion tensor imaging (DTI) in those suffering from headache, but so far only in clinic based samples and with conflicting results.

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Type of headache, frequency of attacks and evolution of headache were investi- gated for an association with white matter fractional anisotropy (FA), mean diffu- sivity (MD), axonal diffusivity (AD), radial diffusivity (RD) and tract volume.

Headache sufferers had widespread higher white matter MD, AD and RD com-

pared to headache free individuals (n = 277).

The effect sizes were mostly small with the largest seen in those with middle-age

onset headache, who also had lower white matter FA.

There were no associations between white matter microstructure and attack fre-

quency or type of headache.

Middle-age onset headache may be related to a widespread process in the white

matter leading to altered microstructure.

Extended: There were no differences in any of the DTI indices between migraine and TTH and no correlation between any of the DTI indices and frequency of head- ache attacks.

There were no differences in any of the DTI indices between those with persis-

tent headache and the headache free.

There were no differences in any of the DTI indices between migraine and TTH and no correlation between any of the DTI indices and frequency of headache attacks (as in Model 1 and 2).

There were no differences in any of the DTI indices between those with persis-

tent headache and the headache free.

There were no differences in any of the DTI indices between migraine and TTH and no correlation between any of the DTI indices and frequency of headache attacks (as in Model 1, 2 and 3).

Background Three previous studies reported no differences in DTI indices between migraine patients and controls using Tract-Based Spatial Statistics (TBSS)[402, 403] or a region-of-interest approach (in the internal capsule and subcortical WM) [404].

Several other studies have found differences in WM microstructure between

headache patients and controls.

Three studies reported higher MD or RD in migraine patients compared to con-

trols in early adulthood using TBSS [405] or DTI tract-average values [406, 407].

Other studies using TBSS reported migraineurs in their teens or early adulthood to have lower MD or RD in several WM regions compared to controls [408–411] and one study [415] also reported decreased AD in several WM regions in migraineurs.

Most of the studies reporting differences in WM microstructure did not correct their analyses for WMH [405, 408, 409, 412–416], which is known to influence DTI measures [417].

The present study aimed to investigate WM microstructure in those suffering from headache in a large sample from the general population where correction for several demographical and clinical variables were available.

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Methods A selection of variables was used to highlight similarities and differences between the various headache groups and the headache free and between the four headache attack frequency groups.

Voxel-wise maps of the FA, MD, AD and RD were calculated for the headache

and control groups.

Those suffering from any headache (in HUNT3) were compared to the headache

free group.

The Fazekas score was excluded as a covariate and clinical variables that were found to be significantly different between the headache sufferers and the headache free (HADS score, presence of chronic pain and consumption of alcohol [the ordi- nal variable] and over-the-counter painkillers) were added (Model 3).

Threshold-free cluster enhancement (TFCE), corrected for multiple comparisons with family-wise error rate (FWE) and thresholded at P < 0.05 (two-tailed), was used to investigate group differences in WM FA, MD, AD and RD.

Results Individuals with previous headache had widespread higher MD and AD in all major WM tracts compared to the headache free, whereas those with persistent headache had higher AD than the headache free, mostly in the left hemisphere in CST, IFOF, ILF and SLF.

Those suffering from new onset headache had significantly higher MD, AD and RD and significantly reduced FA in all major WM tracts compared to the head- ache free.

Adding the Fazekas score as a covariate decreased the number of voxels with higher MD and AD in the any headache group compared to the headache free group, and the RD differences became insignificant.

The new onset headache group had considerably higher MD, AD and RD com-

pared to the headache free group in virtually all major WM tracts.

Discussion The present TBSS analyses showed that those suffering from headache had wide- spread higher WM MD, AD and RD compared to headache free individuals.

The differences in WM microstructure between those with previous or new onset headache and the headache free were to a far lesser degree explained by these variables.

Correction for WMH had virtually no impact on the WM microstructure of those with previous headache and only slightly decreased the difference in WM micro- structure between the new onset headache group and the headache free.

Correcting for HADS, chronic pain, alcohol and over-the-counter painkillers made the FA comparison between the new onset headache group and the headache free insignificant, but did not eliminate the significant differences in MD, AD and RD. The analyses on tract-average DTI indices confirmed the TBSS results of wide- spread WM microstructural differences between the headache free and those suffer- ing from headache, more precisely TTH and/or new onset headache.

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Acknowledgement A machine generated summary based on the work of Kattem Husøy, Andreas; Eikenes, Live; Håberg, Asta K.; Hagen, Knut; Stovner, Lars Jacob. 2019  in The Journal of Headache and Pain.

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