Microstructural changes in the trigeminal nerve of patients with episodic migraine assessed using magnetic resonance imaging

Abstract

Background: There is histological evidence of microstructural changes in the zygomaticotemporal branch of the trigeminal nerve in migraineurs. This raises the possibility that altered trigeminal nerve properties contribute to migraine pathophysiology. Whilst it is not possible to explore the anatomy of small trigeminal nerve branches it is possible to explore the anatomy of the trigeminal root entry zone using magnetic resonance imaging in humans. The aim of this investigation is to assess the microstructure of the trigeminal nerve in vivo to determine if nerve alterations occur in individuals with episodic migraine.

Methods: In 39 migraineurs and 39 matched controls, T1-weighted anatomical images were used to calculate the volume (mm³) and maximal cross-sectional area of the trigeminal nerve root entry zone; diffusion tensor images were used to calculate fractional anisotropy, mean diffusion, axial diffusion and radial diffusion.

Results: There were significant differences between the left and right nerve of controls and migraineurs with respect to volume and not cross-sectional area. Migraineurs displayed reduced axial diffusion in the right nerve compared to the left nerve, and reduced fractional anisotropy in the left nerve compared to left controls. Furthermore, although there were no differences in mean diffusion or radial diffusion, regional analysis of the nerve revealed significantly greater radial diffusion in the middle and rostral portion of the left trigeminal nerve in migraineurs compared with controls.

Conclusions: Migraine pathophysiology is associated with microstructural abnormalities within the trigeminal nerve that are consistent with histological evidence of altered myelin and/or organization. These peripheral nerve changes may provide further insight into migraine pathophysiology and enable a greater understanding for targeted treatments of pain alleviation.

Keywords: Diffusion tensor imaging; Fractional anisotropy; Mean diffusivity; Nerve volume; Trigeminal root entry zone.

Fig. 1

Axial and coronal T1-weighted anatomical images and corresponding diffusion tensor (DTI) images showing the trigeminal nerve root entry zone in a single subject. The DTI image is color-coded for direction of greatest water movement. The outline of the trigeminal nerve region used for total nerve analysis is also shown in red shading on the T1-weighted anatomical image and outlined in white on DTI images. To the right is an example of the regions selected for the rostral (red), middle (yellow) and caudal (green) third of the nerve at the maximal cross-sectional area

Fig. 2

a Plots showing left and right nerve volumes and maximal cross-sectional areas in individual controls (black shading) and migraineurs (grey shading). Horizontal box plots indicate mean (±SEM) for the left and right nerves of each group. Note that only the volume was significantly different, i.e., lower in the right nerve for both controls and migraineurs. *p < 0.05. b Plots showing fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity of the left and right trigeminal root in individual controls and migraineurs. Horizontal box plots indicate mean (±SEM) for the left and right nerves of each group. Note that only fractional anisotropy (FA) and axial diffusivity (AX) was significantly different, i.e., FA was lower in the left nerve of migraineurs than controls and AX was lower in the right nerve than the left nerve in migraineurs. *p < 0.05

Fig. 3

Plots showing linear relationships between the left (grey shading) and right (black shading) total nerve volume, maximum cross-sectional area, fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity in migraineurs with migraine duration, intensity and frequency. Note that there were no significant linear relationships. *p < 0.05

Fig. 4

Line graphs showing mean (±SEM) fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity of the left and right trigeminal root for caudal, middle and rostral divisions in controls (black lines) and migraineurs (grey lines). Note that fractional anisotropy was significantly different, i.e., lower in migraineurs than controls at the middle and rostral divisions, whereas radial diffusivity was greater in migraineurs at the middle and rostral divisions. *p < 0.05. The top panel shows a T1-weighted coronal image with the trigeminal nerve indicated by the red shading. To the left and far right is an expanded view of the left and right trigeminal nerve showing the caudal (green), middle (yellow) and rostral (red) divisions