Imaging of neuroinflammation in migraine with aura
A [11C]PBR28 PET/MRI study
Abstract
Objective
To determine if migraine with aura is associated with neuroinflammation, which has been suggested by preclinical models of cortical spreading depression (CSD) as well as imaging of human pain conditions.
Methods
Thirteen migraineurs with aura and 16 healthy controls received integrated PET/MRI brain scans with [11C]PBR28, a radioligand that binds to the 18 kDa translocator protein, a marker of glial activation. Standardized uptake value ratio (SUVR) was compared between groups, and regressed against clinical variables, using region of interest and whole-brain voxelwise analyses.
Results
Compared to healthy controls, migraineurs demonstrated SUVR elevations in nociceptive processing areas (e.g., thalamus and primary/secondary somatosensory and insular cortices) as well as in areas previously shown to be involved in CSD generation (visual cortex). SUVR levels in frontoinsular cortex, primary/secondary somatosensory cortices, and basal ganglia were correlated with frequency of migraine attacks.
Conclusions
These findings demonstrate that migraine with aura is associated with neuroimmune activation/neuroinflammation, and support a possible link between CSD and glial activation, previously observed in animals.
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© 2019 American Academy of Neurology.
Publication History
Received: July 2, 2018
Accepted: January 7, 2019
Published online: March 27, 2019
Published in print: April 23, 2019
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Study Funding
This work was supported by 5R21NS082926-02 (N.H.), National MS Society RG 4729A2/1, Department of Defense US Army W81XWH-13-1-0112 Award (C.M.), 5T32EB13180 (T32 supporting DSA), NIH R01NS07832201 A1 (C.M.), 1R01NS094306-01A1 (M.L.L.), 1R01NS095937-01A1 (M.L.L.), 1R21NS087472-01A1 (M.L.L.), R61AT009306 (V.N.), R01AR064367 (V.N.), R01AT007550 (V.N.), 1UL1TR001102-01, 8UL1TR000170-05, from the National Center for Advancing Translational Science, and 1UL1RR025758-04, from the National Center for Research Resources, Harvard Catalyst Advanced Imaging Pilot Grant (J.M.H.), Harvard Clinical and Translational Science Center, and financial contributions from Harvard University and its affiliated academic health care centers.
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I read with interest the article by Albrecht et al. on neuroinflammation and migraine with aura (MWA).1 Seven decades after the serendipitous discovery of cortical spreading depression (CSD), no headway has been made in migraine pathophysiology.2,3 Conversely, an adaptive neuroprotective role for CSD has been reported,4,5 while drugs that do not freely cross the blood-brain barrier prevent migraine as well as those that do (a pharmacologic absolute against CSD).2 Pathophysiologically, CSD cannot affect the ophthalmic trigeminal selectively, but the phenotype of migraine most often indicates that such an involvement indeed occurs.2
While the authors acknowledge that the role of neuroinflammation in pain—in general and in migraine in particular—is vague,1 is neuroinflammation confined to the MWA subset? How is neuroinflammation linked to the pathognomonic scintillating scotoma, to the characteristically lateralizing headache, or to the early headache-aborting vomiting of migraine? Until these issues are settled, or until lateralizing neuroinflammation is demonstrated, the conclusion or Albrecht et al.1 that “CSD is now well-accepted as the pathophysiologic mechanism underlying migraine aura” is premature.
In the pathophysiology of migraine, it is important to focus on the first division of the trigeminal nerve, rather than the trigeminal nerve—a major shift in primary headache research.2
Disclosure
The author reports no relevant disclosures. Contact [email protected] for full disclosures.
References