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

DOI: https://doi.org/10.1186/s10194- 018- 0877- 8

Abstract-Summary During the interictal period migraine patients are characterized by abnormal sen- sory information processing, but this functional abnormality may not be sufficient to disrupt the physiological equilibrium of the cortex unless it is accompanied by additional pathological mechanisms, like a reduction in energetic reserves.

The aim of this study was to compare resting cerebral glucose uptake (using positron emission tomography (18fluorodeoxyglucose-PET)), and visual cortex acti- vation (using visual evoked potentials (VEP)), between episodic migraine without aura patients in the interictal period and healthy volunteers.

Twenty episodic migraine without aura patients and twenty healthy volunteers

were studied.

The overall glucose uptake in the visual cortex-to-VEP response ratio was calcu-

lated and compared between the groups.

Standardized glucose uptake values from this region and VEP values from each

subject were then coupled and compared between the groups.

The mean area under the curve of VEP was greater in migraine patients com-

pared to healthy controls.

In the same line, patients had an increased neuronal activation-to-resting glucose

uptake ratio in the visual cortex.

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3 Diagnosis

Statistical parametric mapping analysis revealed that cortical FDG-PET signal in relation to VEP area under the curve was significantly reduced in migraineurs in a cluster extending throughout the left visual cortex, from Brodmann’s areas 19 and 18 to area 7. Within this region, case-wise analyses showed that a visual neuronal activation exceeding glucose uptake was present in 90% of migraine patients, but in only 15% of healthy volunteers.

This study identifies an area of increased neuronal activation-to-resting glucose

uptake ratio in the visual cortex of migraine patients between attacks.

This article has been selected as the winner of the 2018 Enrico Greppi Award. Extended: Studies addressing these issues would be necessary to clarify the pos- sible role of a disruption in cortical homeostasis due to a sensory-metabolic disequi- librium in migraine pathophysiology.

The potential physiopathological implications of such finding should be explored

in depth in future studies.

Background Cortical hyper-responsivity during any kind of sensory stimulus repetition, includ- ing visual, is the most common electrophysiological feature found in episodic migraine patients during the interictal state [448].

The fact that similar cortical reactivity profiles can be found in both migraine patients and their asymptomatic first degree relatives suggests the existence of addi- tional pathologic mechanisms in migraine sufferers that, when associated to visual hyper-responsivity, lead to the development of the disease [449].

FDG-studies in migraine patients between attacks have identified regions of reduced metabolism in limbic areas belonging to the pain/salience matrix [450, 451]. We assessed cerebral glucose uptake, and recorded visual evoked potentials

(VEP) in healthy volunteers and migraine patients.

Our main hypothesis was that the interictal responsivity of the visual cortex in migraine patients would exceed the resting glucose uptake, rendering migraineurs vulnerable to a disruption of metabolic homeostasis in times of increased neuroen- ergetic demands.

Methods Recordings were performed in the electrophysiology laboratory of the Headache Research Unit (Neurology Department, Centre Hospitalier Régional de la Citadelle, Liège, Belgium).

To estimate the neuronal activation-to-overall resting glucose uptake ratio in the visual cortex, eigenvalues corresponding to Brodmann’s areas 17, 18, and 19 were extracted using a volumetric mask.

Based on the statistical parametric mapping results, for case-wise analysis a spe- cific volumetric mask was generated upon the cluster in the visual cortex exhibiting a statistically significant difference in FDG-uptake between groups when including VEP-AUC as a covariate.

For case-wise analyses, mean area under the VEP curve (accounting for visual activity) and eigenvalues corresponding to the specific cluster of the visual cortex exhibiting significant FDG-uptake differences (accounting for metabolic activity) were Z-transformed and paired for each subject.

3.4 Neuroimaging

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Proportions of participants with a visual > metabolic Z-score in each group were

compared using Fisher’s exact test.

Results Four clusters of reduced metabolism where initially observed (uncorrected p < 0.001 level) in the visual cortex of migraine patients, but they did not withstand the correction for multiple comparisons.

Discussion Using 18fluorodeoxyglucose-positron emission tomography acquired at rest and pat- tern reversal-visual evoked potentials, we compared interictal glucose uptake and neuronal activation in the visual cortex of migraine patients and healthy volunteers. By determining an area of sensory-metabolic mismatch (suggestive of the pres- ence of a higher cortical responsivity and relatively lower resting energy reserves) in the visual cortex of migraine patients, our results provide supportive experimen- tal evidence to the initiatory phase of the metabolic strain model.

One cannot discuss cortical metabolism and homeostasis without considering the role of astrocytes (a deficient uptake of glucose by astrocytes could explain our FDG-PET findings in migraine patients based on current evidence [452–454]).

Even if there exists a metabolic imbalance during stimulation in the visual cortex of migraine patients, secondary activation of the trigeminovascular system would need to be further ascertained.

Conclusion Our findings indicate the presence of an area of increased neuronal activation-to- resting glucose uptake ratio in the visual cortex of migraine patients between attacks.

Acknowledgement A machine generated summary based on the work of Lisicki, Marco; D’Ostilio, Kevin; Coppola, Gianluca; Scholtes, Felix; Maertens de Noordhout, Alain; Parisi, Vincenzo; Schoenen, Jean; Magis, Delphine. 2018  in The Journal of Headache and Pain

Topographic changes measured by the swept source optical coherence tomography in retinal nerve fiber layer, optic nerve head and macula in children with migraine