GABA and Glutamate in Pediatric Migraine

Tiffany Bell; Mehak Stokoe; Akashroop Khaira; Megan Webb; Melanie Noel; Farnaz Amoozegar; Ashley D. Harris

Disclosures

Pain. 2020;162(1):300-308. 

In This Article

Results

Participants

Participant demographic data and questionnaire results are shown in Table 1; the final sample sizes were 29 children in the Migraine group and 27 children in the Control group. From the 35 children with migraine recruited, 2 children were excluded because they did not experience a migraine during the past 30 days and 3 children were excluded because they experienced a migraine on the day of the scan. Imaging data were not acquired from 1 child with migraine. From the 31 age- and sex-matched controls recruited, 1 child was excluded because migraines developed shortly after participating in the study, 1 child was excluded due to an ADHD diagnosis, and imaging data were not acquired for 2 control children. Some MRS data were not collected due to children requesting to get out of the scanner, and individual voxel data of poor quality was removed on a case-by-case basis. Table 2 shows the final number of spectra for each voxel included for each analysis. There were no significant differences in data quality (measured using linewidth) between the 2 groups.

Group Comparisons

Thalamus. There were no significant differences in Glx (F(1, 51) = 0.241, P = 0.626), Glu (F(1, 51) = 0.001, P = 0.974), or GABA (F(1, 49) = 0.431, P = 0.515) levels in the thalamus between the 2 groups. There was a trend towards higher GABA/Glx ratios in Migraine (F(1, 48) = 2.950, P = 0.092), mainly driven by higher GABA levels (Figure 2).

Figure 2.

Group comparisons of (A): Glx levels (F(1, 51) = 0.241, P = 0.626); (B): Glu levels (F(1, 51) = 0.001, P = 0.974); (C) GABA levels (F(1, 49) = 0.431, P = 0.515); and (D) GABA/Glx ratios (F(1,48) = 2.950, P = 0.092) in the thalamus. Each circle represents an individual subject.

Sensorimotor Cortex. There were no significant differences between groups in any of the metabolites in the sensorimotor cortex (Glx: F(1, 50) = 0.870, P = 0.356; Glu: F(1, 50) = 1.047, P = 0.311; GABA: F(1, 49) = 0.927, P = 0.340; GABA/Glx: F(1, 47) = 1.258, P = 0.268; Figure 3).

Figure 3.

Group comparisons of (A) Glx levels (F(1,50) = 0.870, P = 0.356); (B) Glu levels (F(1, 50) = 1.047, P = 0.311); (C): GABA levels (F(1, 49) = 0.927, P = 0.340); and (D) GABA/Glx ratios (F(1, 47) = 1.258, P = 0.268) in the sensorimotor cortex. Each circle represents an individual subject.

Visual Cortex. There were no significant differences in Glx (F(1, 48) = 1.989, P = 0.165), Glu (F(1, 48) = 2.812, P = 0.100), GABA (F(1, 48) = 0.582, P = 0.449), or GABA/Glx ratios (F(1, 47) = 1.276, P = 0.264; Figure 4) in the visual cortex between the 2 groups.

Figure 4.

Group comparisons in (A): Glx levels (F(1, 48) = 1.989, P = 0.165); (B): Glu levels (F(1, 48) = 2.812, P = 0.100); (C): GABA levels (F(1, 48) = 0.582, P = 0.449); and (D) GABA/Glx ratios (F(1, 47) = 1.276, P = 0.264) in the visual cortex. Each circle represents an individual subject.

Aura: Of the 25 children with migraine included in the visual cortex analyses, 9 reported aura either before or during their migraine, 15 reported no aura, and 1 participant did not specify (who was removed from the following analysis). There was a significant effect of group on Glu levels (F(2, 46) = 3.317, P = 0.045) when comparing children with migraine and aura, children with migraine without aura, and controls. Levels of Glu were significantly lower in migraine with aura (P = 0.022) compared to Controls (Figure 5). There were no significant differences in GABA (F(2, 46) = 0.458, P = 0.635), Glx (F(2, 46) = 2.798, P = 0.071), or GABA/Glx ratios (F(2, 45) = 1.024, P = 0.367) in the visual cortex between the 3 groups.

Figure 5.

Glu levels in Migraine with and without aura, and Controls. Migraine with aura had significantly lower glutamate levels in the visual cortex compared to Control (P = 0.019). There was no significant difference between Migraine without aura and control (P = 0.135) or between the Migraine with and without aura groups (P = 0.324).

Migraine Characteristics

In Migraine, higher glutamate levels in the thalamus (r(17) = 0.514, P = 0.025, Figure 6A) and higher GABA/Glx ratios in the sensorimotor cortex (r(15) = −0.562, P = 0.019, Figure 6B) were associated with a greater number of years with migraine.

Figure 6.

Associations between migraine characteristics and neurochemical levels. (A) Positive correlation between Glu in the thalamus and the number of years with migraine, controlling for age (r(18) = 0.532, P = 0.016). (B) Negative correlation between the GABA/Glx ratio in the thalamus and the number of years with migraine, controlling for age (r(17) = −0.456, P = 0.05). (C) Positive association between GABA in the thalamus and the PedMIDAS score, controlling for age (r(23) = 0.370, P = 0.068). (D) Positive correlation between GABA in the sensorimotor and the PedMIDAS score, controlling for age (r(24) = 0.514, P = 0.007). (E) Positive association between GABA in the visual cortex and the PedMIDAS score, controlling for age (r(22) = 0.361, P = 0.084). Gray shading indicates the 95% confidence intervals on the partial correlations.

In Migraine, higher levels of GABA in the sensorimotor cortex were associated with higher PedMIDAS scores (r(23) = 0.516, P = 0.008, Figure 6D), indicating children with higher GABA levels were more impacted by their migraines. This association was also seen in the thalamus and visual cortex but did not reach statistical significance. (thalamus: r(22) = 0.365, P = 0.080, visual cortex: r(21) = 0.352, P = 0.099, Figures 6C and E).

Migraine Cycle. In Migraine, lower GABA (and, consequently, GABA/Glx) levels in the thalamus were associated with being further along in the migraine cycle and subsequently, closer to the next migraine (GABA: r(15) = −0.507, P = 0.038, Figure 7; GABA/Glx: r(15) = −0.559, P = 0.020).

Figure 7.

Negative correlation between levels of GABA in the thalamus and the position of the child in their migraine cycle, controlling for age (r(16) = −0.499, P = 0.035).

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....