The role of the supratentorial neural network involved in addiction in patients with medication overuse headache in comparison to patients with chronic and episodic migraine.
Final Report Abstract
In Project 1 (MOH-CM study), we aimed at assessing the supratentorial neural network involved in addiction in patients with medication overuse headache (MOH) in comparison to patients with chronic (CM) and episodic migraine (EM). The hypotheses were that the brain of patients with MOH overusing triptans (but not others, such as opioids or recreational drugs) examined by VBM and DTI differs from the brain of patients with CM and / or EM. Despite major efforts, I have not been able to recruit a sufficient number of subjects with MOH overusing triptans in the entire period of the fellowship. This was likely due to a major cultural difference between Europe and the US with a significantly higher number of MOH patients overusing opioids or using illegal drugs, such as marijuana. In order to study the neural network of addiction in subjects with MOH, the intake of prophylactics and especially addictive substances (opioids for pain medication and marijuana) was exclusion criterion in the initial application. A collaborator is currently completing a subgroup of the study (CM and EM patients). Deviations from the initial plan were therefore necessary as also described in Project 2 and 3. In Project 2 (DHE study), we tested the hypothesis that a breakdown of the blood-brain barrier (BBB) occurs during migraine attacks to help migrainespecific medications, such as dihydroergotamine (DHE), to get access to the central sites of action. Six pain-free migraineurs fulfilling the criteria for episodic migraine were examined with dynamic positron emission tomography (PET) using the radioligand [11C]-dihydroergotamine ([11C]DHE). The influx rate constant K, as a measure of parenchymal binding in the brain and thus BBB penetration was calculated using the arterial blood input function. The influence of glyceryl trinitrate (GTN)-induced migraine headache was assessed in a second 11C]DHE scan comparing the K, maps between migraineurs (during migraine and at baseline) and controls (after GTN infusion and at baseline). Migraineurs and controls showed binding of [11C]DHE at the choroid plexus, the pituitary gland, and the venous sinuses. There was no binding [K1 = 0/min] in the brain parenchyma including the area with the highest density of the highest-affine DHE receptor (hippocampus) and the likely brainstem sites of action during migraine (periaqueductal grey, raphe nuclei). This pattern was unchanged during migraine attacks, DHE is neither able cross the BBB interictally nor ictally. This suggests that the BBB remains tight for DHE during migraine headaches. In addition to aiming at the right central structure to terminate acute migraine attacks, future medications should be able to cross the BBB by themselves. In Project 3 (VS-study), we characterized the clinical phenotype of patients reporting continuous tiny dots in the entire visual field similar to the noise of an analogue television also known as 'visual snow'. Using chart review (n = 22) and Internet survey (n = 275), we identified a clinical syndrome that was subsequently confirmed in 78 patients with normal ophthalmological exam out of 142 participants in a prospective semi-structured telephone interview. We found that 'visual snow' is typically associated with palinopsia (trailing and afterimages), entoptic phenomena (floaters, blue field entoptic phenomenon, spontaneous photopsia, self-light of the eye), photophobia, and nyctalopia (impaired night vision) suggesting a unique visual disturbance clinically very distinct from migraine aura. Migraine is a common concomitant although the standard migraine treatments are most often unhelpful. When compared to healthy controls, 20 'visual snow' patients showed hypermetabolism in the right lingual gyrus in [18F]-2-fluor-2-desoxy-D-glucose positron emission tomography (FDG PET) and, in proximity, increased gray matter volume in the fusiform gyrus (both Brodmann area 19) using voxel-based morphometry (VBM). There was no difference in the primary visual cortex. This suggests that 'visual snow' is an organic disorder involving a dysfunction of the supplementary visual cortex. The right lingual and fusiform gyri might not only be involved in photophobia in migraineurs, but also in the suppression of VS, after-images, entoptic phenomena and photophobia to assure clear vision.
Publications
- Field-testing the criteria for visual snow (positive persistent visual disturbance). Headache. 2012;52(5):898
Schankin CJ, Maniyar FH, Goadsby PJ
- Visual snow: a new disease entity distinct from visual snow. Neurology, 2012 [Abstract at the annual meeting of the American Academy of Neurology, New Orleans]
Schankin CJ, Maniyar FH, Hoffmann J, Chou D, Goadsby PJ
- Brain activations in the premonitory phase of nitroglycerin triggered migraine attacks. Brain. 2013. [Epub ahead of print]
Maniyar FH, Sprenger T, Monteith T, Schankin C, Goadsby PJ
- Transient Exacerbation of Headache in Patients Receiving Intravenous Dihydroergotamine for Inpatient Management of Chronic Migraine. Cephalalgia. 2013;33[Suppl 8]:63
Eller M, Riggins NY, Church MM, Schankin CJ, Goadsby PJ
