Migraine characteristics:
Migraineurs reported their pain distribution commonly experienced during a migraine attack over the last 12 months as mostly confined to the orofacial region and occasionally the neck. Sixteen migraineurs reported that their headaches were normally unilateral in nature whereas the remaining 18 migraineurs reported them to be primarily bilateral. Migraine subjects most frequently described their migraine pain as “throbbing,” “pulsating,” and/or “sharp” in nature. They indicated that “stress,” “lack of sleep,” and/or “bright light” most often triggered their migraine attacks. The mean (±SEM) length of time since the onset of migraine attacks was 16.0±1.9 years, the mean estimated frequency of migraine attacks was 2.4±0.4 per month, and the mean pain intensity of migraines as measured by the 6-point visual analogue scale was 3.8±0.2. Although 23 of 39 were taking some form of daily medication (mostly the oral contraceptive pill; 15 migraineurs), none of the migraine subjects were taking prophylactic medication for migraine.
Trigeminal nerve volume and maximum cross-sectional analysis:
Analysis of trigeminal nerve root entry zone volumes revealed that in both controls and migraineurs, total volume of the left nerve was significantly larger than that of the right nerve (controls: p<0.001; migraine: p<0.001) (Figure 2A, Table 1). There was however no significant difference between left nerves in migraineurs compared with controls (p=0.62) and similarly no difference between the right nerves (p=0.79). In contrast, there were no significant differences between the left and right maximal cross-sectional areas in controls (p=0.38) or migraineurs (p=0.89) or between the left nerves (p=0.41) or right nerves (p=0.70) between groups. Additionally, there were no significant linear relationships between volume and either migraine duration (r=0.05, p=0.77) or intensity (r=0.26, p=0.12) or frequency (r=0.01, p=0.94) or between maximal cross-sectional area and either migraine duration (r=0.19, p=0.26) or intensity (r=0.28, p= 0.08) or frequency (r=0.12, p=0.48) (Figure 3). Furthermore, there were no significant linear relationships between the volume of the nerve ipsilateral or contralateral to the side of pain and either migraine duration (ipsi: r=-0.17, p=0.49; contra: r=0.28, p=0.25) or intensity (ipsi: r=0.19, p=0.44; contra: r=0.44, p=0.06) or frequency (ipsi: r=0.11,p=0.64; contra: r=-0.08, p=0.75) or maximal cross-sectional area and either migraine duration (ipsi: r=-0.13, p=0.58; contra: r=0.12, p=0.63) or intensity (ipsi: r=0.38, p=0.12; contra: r=0.40, p=0.09) or frequency (ipsi: r=0.37, p=0.12; contra: r=0.28, p=0.24). Intra-tracer reliability for global volumes had a mean Cronbach's alpha of 0.98 (95%CI: 0.92, 0.99) and a mean±SEM Dice similarity coefficient of 0.81±0.04. Inter-tracer reliability for global volumes had a mean Cronbach's alpha of 0.96 (95%CI: 0.85, 0.99) and a mean±SEM Dice similarity coefficient of 0.80±0.04.
|
Controls
|
Migraineurs
|
|
(n = 39)
|
(n = 39)
|
|
Left
|
Right
|
Left
|
Right
|
Total nerve volume (mm3)
mean (±SEM)
|
108.77 (3.97)*
|
96.32 (3.56)
|
105.86 (4.37)*
|
94.90 (4.05)
|
Maximum cross-sectional area (mm2)
mean (±SEM)
|
3.81 (.12)
|
3.74 (.10)
|
3.67 (.12)
|
3.68 (.11)
|
Table 1. Overall mean (SEM) volume and maximum cross-sectional area of the trigeminal root entry zone in control and migraine subjects.
Note that there was a significant difference between the left and right nerves of the control and left and right nerves of the migraine group. * p<0.05, significant within group difference between left and right nerve volumes.
Trigeminal nerve diffusion analysis:
One control and migraine subject were excluded from the trigeminal nerve diffusion analysis due to the absence of a clearly visible nerve boundary. Analysis of the remaining 38 subjects revealed significant differences between the left FA values of the controls and the left migraineurs (p=0.01) with migraineurs displaying significantly reduced FA compared with controls (Figure 2B, Table 2). In contrast, whilst in controls there were no significant differences in MD (p=0.89), AX (p=0.48), FA (p=0.13) or RD (p=0.93) between the left and right nerves, in migraineurs the magnitude of AX was significantly lower in the right nerve compared with the left (p=0.04) with no significant differences in MD (p=0.01), FA (p=0.06) and RD (p=0.01). However, overall, there were no significant differences between the left control and left migraineur values or between total MD (p=0.12), AX (p=0.20) or RD (p=0.12) and right control and right migraineur values or between total MD (p=0.67), AX (p=0.73), FA (p=0.21) or RD (p=0.58) nerve volumes between controls and migraineurs. Additionally, there were no significant linear relationships between any of the four diffusion measures and either migraine duration (FA r=0.02, MD r=0.01, AX r=0.01, RD r=-0.01) or intensity (FA r=-0.01, MD r=0.23, AX r=0.26, RD r=0.01) or frequency (FA r=-0.08, MD r=-0.03, AX r=-0.11, RD r=0.12) (Figure 3). Finally, there were no significant linear relationships between any of the four diffusion measures of the nerve ipsilateral and contralateral to the side of pain and either migraine duration (FA ipsi: r=0.17, p=0.51; contra: r=-0.28, p=0.24; MD ipsi: r=-0.36, p=0.15; contra: r=-0.01, p=0.96; AX ipsi: r=-0.38, p=0.12; contra: r=-0.06, p=0.80; RD ipsi: r=-0.19, p=0.44; contra: r=0.02, p=0.60), migraine intensity (FA ipsi: r=0.04, p=0.88; contra: r=-0.12, p=0.66; MD ipsi: r=-0.21, p=0.41; contra: r=0.29, p=0.23; AX ipsi: r=-0.22, p=0.38; contra: r=0.29, p=0.24; RD ipsi: r=-0.19, p=0.45; contra: r=0.29, p=0.23), or migraine frequency (FA ipsi: r=-0.06, p=0.81; contra: r=0.01, p=0.97; MD ipsi: r=0.23, p=0.37; contra: r=0.12, p=0.64; AX ipsi: r=0.21, p=0.40; contra: r=0.09, p=0.70; RD ipsi: r=0.30, p=0.22; contra: r=0.13, p=0.60).
Trigeminal nerve caudal, middle and rostral divisions analysis:
Analysis of caudal, middle and rostral segments of the left and right trigeminal nerves revealed significant differences in FA with reduced FA in migraineurs compared with controls for the left nerve at the middle and rostral divisions (left FA: caudal p=0.07; middle p=0.003; rostral p=0.0004; right FA: caudal p=0.175; middle p=0.279; rostral p=0.077) (Figure 4, Table 2). ) Furthermore, the left and right nerve analysis revealed a significantly greater RD value in migraineurs compared with controls for the left nerve at the middle and rostral divisions (left RD: caudal p=0.61; middle p=0.04; rostral p=0.04; right RD: caudal p=0.94; middle p=0.44; rostral p=0.36). In contrast, at no division was MD (left MD: caudal p=0.81; middle p=0.17; rostral p=0.15; right MD: caudal p=0.59; middle p=0.37; rostral p=0.16) or AX (left AX: caudal p=0.92; middle p=0.60; rostral p=0.53; right AX: caudal p=0.55; middle p=0.92; rostral p=0.92) significantly different between controls and migraineurs.
Table 2. Fractional anisotropy, mean diffusion, axial diffusion and radial diffusion values of the trigeminal nerve root entry zone in control and migraine subjects. Total nerve as well as caudal, middle and rostral third values are shown. * p<0.05, significant within group difference between left and right nerve volumes. # p<0.05, significant between group difference between left and right nerve volumes.
|
Controls
|
Migraineurs
|
|
(n = 38)
|
(n = 38)
|
|
Left
|
Right
|
Left
|
Right
|
Fractional anisotropy
(mean [±SEM])
|
|
Total nerve
|
.26 (.01)#
|
.25 (.01)
|
.23 (.01)
|
.24 (.01)
|
Caudal third
|
.24 (.01)
|
.24 (.01)
|
.22 (.01)
|
.23 (.01)
|
Middle third
|
.28 (.01)#
|
.27 (.01)
|
.25 (.01)
|
.26 (.01)
|
Rostral third
|
.25 (.01)*#
|
.24 (.01)
|
.22 (.01)*
|
.22 (.01)
|
Mean diffusion
(mean [±SEM] ×10-3 mm2/sec)
|
|
Total nerve
|
2.52 (.04)
|
2.51 (.05)
|
2.61 (.04)
|
2.54 (.04)
|
Caudal third
|
2.64 (.06)
|
2.62 (.06)
|
2.66 (.06)
|
2.67 (.06)
|
Middle third
|
2.44 (.04)
|
2.43 (.05)
|
2.53 (.05)
|
2.50 (.05)
|
Rostral third
|
2.59 (.05)
|
2.50 (.07)
|
2.70 (.05)
|
2.62 (.05)
|
Axial diffusion
(mean [±SEM] ×10-3 mm2/sec)
|
|
Total nerve
|
3.22 (.05)
|
3.17 (.06)
|
3.23 (.05)*
|
3.14 (.04)
|
Caudal third
|
3.26 (.07)
|
3.27 (.07)
|
3.25 (.07)
|
3.22 (.06)
|
Middle third
|
3.14 (.05)
|
3.12 (.06)
|
3.18 (.06)
|
3.11 (.05)
|
Rostral third
|
3.24 (.06)
|
3.13 (.08)
|
3.29 (.06)*
|
3.14 (.05)
|
Radial diffusion
(mean [±SEM] ×10-3 mm2/sec)
|
|
Total nerve
|
2.21 (.04)
|
2.19 (.05)
|
2.30 (.04)
|
2.13 (.08)
|
Caudal third
|
2.34 (.06)
|
2.34 (.06)
|
2.38 (.06)
|
2.35 (.06)
|
Middle third
|
2.09 (.04)#
|
2.09 (.05)
|
2.22 (.05)
|
2.14 (.05)
|
Rostral third
|
2.27 (.05)#
|
2.20 (.06)
|
2.42 (.05)*
|
2.27 (.05)
|