Migraine Brain Imaging Marker May Aid Diagnosis

January 29, 2020

A neural marker for migraine without aura has been identified on functional magnetic resonance imaging (fMRI), which could become a tool to help in the diagnosis of the condition.

"While most patients will not need to have an fMRI to diagnose migraine, there are some patients in which the diagnosis is uncertain, and then this could be helpful. It would be useful to have objective evidence," senior author Jian Kong, MD, Massachusetts General Hospital and Harvard Medical School, Charlestown, told Medscape Medical News.

"The results also help us better understand the mechanisms of migraine and could therefore have implications for developing new treatments for migraine, as they have identified certain areas of the brain that we need to target," he said. 

"The key finding is that connections are particularly different in the occipital region of the brain," he said, noting that this area is traditionally associated with visual stimulation.

"We have known that the occipital area is important in migraine, but our study shows that certain connections in this area are highly specific to patients with migraine and can be used as a marker to distinguish migraine from patients with other types of chronic pain," he added.

The study was published online January 21 in Neurology.

Using a machine-learning approach and resting-state fMRI images, the authors identified a map of functional brain connections, which could discriminate patients with migraine without aura from controls with an accuracy ranging from 84% to 91%.

"There have been similar studies, but we believe this is the most comprehensive so far as we compared different cohorts of patients to different controls and to patients with other pain disorders," Kong noted.

For the first study, 70 patients with migraine without aura and 46 demographically matched healthy controls underwent resting-state fMRI. The brain was divided into 160 different areas and connections between each area were analyzed using a machine-learning tool.

This showed differences between patients with migraine and healthy controls, and identified a neural marker with abnormal functional connectivity within the visual, default mode, sensorimotor, and frontal-parietal networks that could discriminate migraineurs from healthy controls with 93% sensitivity and 89% specificity.

To investigate the generalizability of the marker, researchers applied it to an independent cohort of 19 migraineurs and 19 healthy controls, and found a sensitivity and specificity of 84%.

In a third study, the marker was used to distinguish between 18 different patients with migraine and 28 patients with other chronic pain disorders, including chronic low back pain and fibromyalgia, and demonstrated 78% sensitivity and 76% specificity in this regard.

In a fourth analysis, the original 70 migraine patients from the first study were rescanned after 4 weeks, with 67 of the patients correctly classified as migraineurs (sensitivity 95.7%), which the authors say indicates "a good test-retest reliability."

In addition, during the 4-week period between the two scans, patients received treatment with real or sham acupuncture. The real acupuncture group showed a modulation of the brain marker, whereas the sham acupuncture group did not show any changes in the marker.

"These results suggest that acupuncture could possibly target the network involved in the brain in patients with migraine," Kong said. 

"This is a first step. Our results need to be further validated in other cohorts and larger sample sizes," he commented.  

"We cannot tell if these different brain connections in migraine patients are causal for migraine or just a marker. Our study was not able to address that," he added.

In an accompanying editorial, Maria Rocca, MD, Judith Harrer, MD, IRCCS San Raffaele Scientific Institute, Milan, Italy, and Massimo Filippi, MD, RWTH Aachen University Hospital, Germany, say the study provides evidence of core network alterations specifically associated with migraine, which they describe as "a substantial merit."

They point out that the marker was not able to distinguish patients with fibromyalgia and low back pain from their matched controls supporting its strict relation to the pathophysiology of migraine.

The editorialists note that diagnosis of migraine is based mainly on taking a good clinical history, and although this is unlikely to change in routine clinical practice, these emerging magnetic resonance techniques could help clinicians to discriminate those patients who have challenging clinical presentations, such as probable migraine versus tension-type headache or chronic migraine versus hemicrania continua, and patients who may not respond to therapy, thus improving diagnostic workup and patient management.

These techniques could also help to improve the quality of future migraine therapy studies by ruling out the inclusion of patients with nonmigrainous headache, they suggest.

They add that the study provides new insights into the neural mechanism of migraine, and the techniques used will help elucidate the central mechanisms of the action of new treatments, predict treatment response, and identify novel therapeutic targets.

The study was funded by grants from the National Institutes of Health/National Center for Complementary and Integrative Health and the National Natural Science Foundation of China. Kong and colleagues, as well as Rocca, have reported no relevant financial relationships. Harrer has reported receiving speaker honoraria from Teva and Novartis. Filippi has reported receiving compensation for consulting services/speaking activities from Novartis.

Neurol. Published online January 21, 2020. Abstract, Editorial

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