Occipital Levels of Gaba Are Related to Severe Headaches in Migraine

Abstract

Although GABA has figured prominently in theories of migraine pathogenesis, 1 brain levels of this transmitter have not been directly measured in migraineurs. This is of importance since, in migraine, neurophysiologic events account for brain hyperexcitability and subcortical disinhibition. 2,3 Magnetic resonance spectroscopy (MRS) measures levels of metabolites in the human brain and may map regional changes in their levels. 4 Accordingly, herein we used MRS to measure the levels of GABA in individuals with migraine with aura (MA), migraine without aura (MO), and in controls. MethodsIndividuals with MA (n = 9), MO (n = 10), and controls without headache (n = 9) were enrolled. Participants could not use migraine preventive drugs or any other on a daily basis. Subjects prospectively collected their headache information over 1 month, using a daily headache calendar. Disability was assessed with the Migraine Disability Assessment Questionnaire (MIDAS).Migraineurs were imaged no less than 72 hours after their last headache attack. Data were acquired at 4T using a MRS INOVA system. Details of the methods are described elsewhere. 5 Briefly, a volume of 3 × 3 × 1.5 cm 3 was used positioned within the midline of the occipital lobe using inversion recovery gradient echo images. Two 8.5-minutes acquisition were averaged to generate a final GABA spectrum, referenced to creatine (Cr) and to N-acetylaspartate (NAA).We conducted cross-sectional analysis examining occipital GABA levels by headache status. We also evaluated the relationship between GABA levels and variables prospectively obtained from headache diaries (e.g., severe headaches). We powered our study based on assumptions for the GABA levels, as published previously. 6 We had an 80% power to detect 15% change in the GABA levels in a two-sided t test. This study was approved by the Tables 1 and 2 display the GABA concentration (millimoles per liter), GABA/Cr ratio, and total GABA (millimoles), across the different groups. The differences were not significant. For GABA, the mean values were 0.61 mmol (95% CI = 0.49-0.75) in controls, 0.67 mmol (95% CI = 0.56 -0.78) in the MO group, and 0.74 mmol (95% CI = 0.58-0.89) in the MA group. Nonsignificant differences were found in the other variables as well.Pooling the MO and MA subjects, GABA concentration was lower in individuals with severe headaches in the previous month. In those with no severe headaches, it was 0.72 ± 17 mmol/L vs 0.52 ± 0.64 mmol/L in those with one or more (p = 0.03). It was also lower in individuals with headaches of at least moderate severity. Finally, migraineurs with impairment (MIDAS grades II to IV) had lower GABA concentrations compared to those with no impairment (0.50 ± 0.48 mmol/L vs 0.73 ± 15 mmol/L, p < 0.05). After scaling by the creatine and NAA content, the findings were similar. For example, GABA/Cr ratio was also significantly lower in those with severe headaches in the past month (0.056 ± 0.08 mmol/L vs 0.068 ± 0.017 mmol/L, p = 0.04). DiscussionWe found that the levels of GABA ...

Elevated levels of GABA+ in migraine detected using 1H‐MRS

“…The results of post‐hoc analyses, showing no statistically significant correlation between GABA+ concentration and headache severity, differ from those of an earlier report indicating lower GABA levels in individuals with migraine with severe headaches . We believe that this difference in findings may be explained by the lack of variability in headache intensity of our participants (Table ).…”

Biochemistry of primary headaches: role of tyrosine and tryptophan metabolism

“…Drugs GABA agonist such as valproate and topiramate are very effective in the preventing the migraine without aura attacks [49]. However, direct evidence of GABA-related abnormalities in migraine is poor [50]. One study has shown that plasma levels of GABA increase at the end of migraine attack.…”

Gamma‐Aminobutyric Acid (Gaba) Receptors Rho (Gabrr) Gene Polymorphisms and Risk for Migraine

“…The implication of GABA in the pathogenesis of migraine is supported by several biochemical, pharmacological, neurophysiological, and experimental data, that are summarized in the Table (data included in this table were selected from those obtained through a PubMed Search crossing the terms “migraine” with “GABA” or “gamma‐aminobutyric acid” from 1966 to March 15, 2017, that retrieved a total of 271 references).…”

“…9 Bridge et al 10 reported decreased GABA levels in the occipital cortex of 13 females with migraine with visual aura patients when compared with 13 female controls. Bigal et al 11 found no significant differences in occipital GABA levels between migraineurs (9 with and 10 without aura) and controls, or between patients with migraine with or without aura, although they found a trend toward lower GABA concentration in individuals with severe headaches in the previous month. Kono et al 12 found a significant decrease in 11 C-flumazenil binding (a marker of GABA A receptors) in the cerebellum of 3 patients with familial hemiplegic migraine type 1 associated with the CACNA1A gene mutation compared with the normal controls.…”