Cortical metabolic and structural differences in patients with chronic migraine. An exploratory 18FDG-PET and MRI study

DOI: https://doi.org/10.1186/s10194- 021- 01289- 5

Abstract-Summary To describe interictal brain structural and metabolic differences between patients with episodic migraine (EM), chronic migraine (CM) and healthy controls (HC).

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This is an exploratory study including right-handed age-matched women with

EM, CM and HC.

Fifteen patients (8 EM, 7 CM) and 11 HC were included. Morphometric data showed an increased CTh in 6 frontal areas (L/R-Caudal Middle Frontal, L/R-Rostral Middle Frontal, L-Medial Orbitofrontal and L-Superior Frontal) in CM patients compared to HC without differences for IGI.

Adjusted analysis in CM showed a statistically significantly hypometabolism in 9 frontal areas (L-Lateral Orbitofrontal, L/R-Medial Orbitofrontal, L-Frontal Superior, R-Frontal pole, R-Parts Triangularis, L/R-Paracentral and R-Precentral) and 7 temporal areas (L/R-Insula, L/R-Inferior temporal, L/R-Temporal pole and R-Banks superior temporal sulcus) compared to HC.

EM patients presented intermediate metabolic values between EM and HC

(non-significant).

CM patients showed frontotemporal hypometabolism and increased frontal cor- tical thickness when compared to HC that may explain some cognitive and behav- ioural pain-processing and sensory integration alterations in CM patients.

Extended: EM patients presented intermediate CTh values between CM and HC for the previous areas; only CTh values for right pars opercularis, right transverse temporal and right temporal pole were statistically significant thinner in EM in comparison to HC.

EM patients presented higher metabolic activity than CM but lower than HC for

these regions which follows a headache frequency-related spectrum of change.

CM patients showed higher scores in headache-disability MIDAS scale (EM: 9.5 [29.0] vs. CM: 32.0 [89.0], p  =  0.039) although results from headache impact (HIT6) and quality of life (MSQ) were comparable between patients.

CM patients showed temporal hypometabolic areas compared with HC. CM patients showed a lower glucose metabolic activity compared to HC for a cluster of the left temporal lobe, which includes the left fusiform, left middle tem- poral, left inferior temporal, left temporal pole, bilateral insula and superior tempo- ral sulcus.

Background Advanced neuroimaging could help us to better understand which brain structures are involved in migraine pathophysiology as well as to find potentially useful migraine imaging biomarkers [442].

Previous MRI studies have highlighted that brain regions with a key role in migraine attack generation, like the pons and hypothalamus might also be involved in migraine chronification [443–447].

18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG-PET) is used

to produce images of metabolic activity of the brain.

In migraine, 18 F-FDG-PET studies have identified disease or attack-specific

alterations in brain activity within the migraine brain [378].

The aim of this study was to describe interictal brain metabolic and structural differences in a controlled and homogeneous population of patients with episodic migraine (EM), CM and healthy controls (HC).

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Methods Clinical differences between EM and CM were assessed by independent t-test for continuous variables that followed a normal distribution (headache and analgesic frequencies, migraine evolution, HIT-6 and MSQ) and, Mann-Whitney U test was used for the rest of continuous variables (MIDAS).

Metabolic (18 F-FDG-PET) and structural (CTh and lGI) values were analyzed using a pre-planned one-way ANCOVA, adjusted for the effect of age, for the study groups (EM, CM and HC).

Following significant group main effects, post-hoc analysis was conducted using the Bonferroni correction in order to find differences in the neuroimaging variables (18 F-FDG-PET, CTh and lGI) between EM, CM and HC.

18 F-FDG-PET measurements between groups were also analyzed adjusting by patient’s age and their CTh and lGI values in order to study if metabolic activity was influenced by brain structure.

Results CM patients showed a lower glucose metabolic activity compared to HC for a clus- ter of the left temporal lobe, which includes the left fusiform, left middle temporal, left inferior temporal, left temporal pole, bilateral insula and superior tempo- ral sulcus.

Only the metabolic activity for the bilateral temporal pole in EM showed statisti-

cally significant differences compared to HC.

EM patients presented intermediate CTh values between CM and HC for the previous areas; only CTh values for right pars opercularis, right transverse temporal and right temporal pole were statistically significant thinner in EM in compari- son to HC.

With HC, we found that CM presented and hypometabolism in several frontal regions: left lateral orbitofrontal, bilateral medial orbitofrontal, bilateral paracen- tral, left superior frontal and right frontal pole.

For the temporal lobe, statistically significant differences were also found in right superior temporal sulcus, bilateral inferior temporal, bilateral temporal pole and bilateral insula between HC and CM.

Discussion This is the first study which explores metabolic and structural differences in migraine patients combining PET and MRI techniques.

Our results suggest that CM patients show cortical frontotemporal structural and

metabolic differences when compared to HC.

It is important to point out that we have included structural data to adjust cortical metabolism analysis, and we have found that the structural adjusted 18 F-FDG-PET values may increase the sensitivity of the model, showing more areas with statistical differences than the non-adjusted model.

Cortical metabolism values in EM patients were in between HC and CM for all

areas, except for right temporal pole.

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This is the first study that explores metabolic and structural differences in migraine patients combining PET and MRI techniques, that were done on the same day, avoiding any possible biases in relation to natural migraine fluctuations.

Conclusions CM is correlated with brain metabolic and structural differences.

EM patients presented higher metabolic activity than CM but lower than HC for

these regions which follows a headache frequency-related spectrum of change.

Metabolic data analysis using precise structural anatomical information allowed

us to obtain more accurate models.

Acknowledgement A machine generated summary based on the work of Torres-Ferrus, Marta; Pareto, Deborah; Gallardo, Victor J; Cuberas-Borrós, Gemma; Alpuente, Alicia; Caronna, Edoardo; Vila-Balló, Adrià; Lorenzo-Bosquet, Carles; Castell-Conesa, Joan; Rovira, Alex; Pozo-Rosich, Patricia. 2021 in The Journal of Headache and Pain.

Evidence of an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients: a study comparing 18FDG-PET and visual evoked potentials