Anders Hougaard

Experimentally induced hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura (MA). We investigated the blood oxygenation level-dependent (BOLD) signal response to visual stimulation during hypoxia in MA patients and healthy volunteers. In a randomized double-blind crossover study design, 15 MA patients were allocated to 180 min of normobaric poikilocapnic hypoxia (capillary oxygen saturation 70-75%) or sham (normoxia) on two separate days and 14 healthy volunteers were exposed to hypoxia. The BOLD functional MRI (fMRI) signal response to visual stimulation was measured in the visual cortex ROIs V1-V5. Total cerebral blood flow (CBF) was calculated by measuring the blood velocity in the internal carotid arteries and the basilar artery using phase-contrast mapping (PCM) MRI. Hypoxia induced a greater decrease in BOLD response to visual stimulation in V1-V4 in MA patients compared to controls. There was no group difference in hypoxia-induced total CBF...

To assess bone regeneration in critical sized defects in the rabbit calvarium, filled with the bone substitute calcium phosphate cement. Circular bone defects (8mm) were made in both parietal bones of 10 rabbits. One of the defects was filled with the calcium phosphate cement, and the other received autogenous bone harvested from the calvaria. The animals were killed at 3 or 6 weeks (n=5). Data analysis included qualitative assessment of the calvarial specimens and histomorphometric analysis was used to quantify the amount of new bone within the defects. The microscopic analysis of the samples showed bone healing with both calcium phosphate cement and autogenous bone graft. Data obtained from the histomorphometric analysis were statistically analyzed using 2-way analysis of variance and the Tukey's test. Data analysis showed that the autogenous bone graft had significantly more new bone compared with calcium phosphate cement at 3 and 6 weeks. Calcium phosphate cement at 6 weeks presented similar results to autogenous bone at 3 weeks. Both treatments presented an increase in bone healing with time. Treatments allowed bone regeneration that increased with time, however surgical cavities treated with the autogenous graft had more bone formation than those with calcium phosphate cement.

In 2000, the Clinical Trials Subcommittee of the International Headache Society (IHS) published the second edition of its guidelines for controlled trials of drugs in migraine. The purpose of this publication was to improve the quality of such trials by increasing the awareness amongst investigators of the methodological issues specific to this particular illness. Until now the adherence to these guidelines has not been systematically assessed. We reviewed all published controlled trials of drugs in migraine from 2002 to 2008. Eligible trials were scored for compliance with the IHS guidelines by using grading scales based on the most essential recommendations of the guidelines. The primary efficacy measure of each trial was also recorded. A total of 145 trials of acute treatment and 52 trials of prophylactic treatment were eligible for review. Of the randomized, double-blind trials, acute trials scored an average of 4.7 out of 7 while prophylactic trials scored an average of 5.6 out of 9 for compliance. Thirty-one percent of acute trials and 72% of prophylactic trials used the recommended primary efficacy measure. Fourteen percent of the reviewed trials were either not randomized or not double-blinded. Adherence to international guidelines like these of IHS is important to ensure that only high-quality trials are performed, and to provide the consensus that is required for meta analyses. The primary efficacy measure for trials of acute treatment should be “pain free” and not “headache relief”. Open-label or non-randomized trials generally have no place in the study of migraine drugs.

Specific problems occur in clinical treatment trials for migraine with aura that differ from those encountered in treatment trials for migraine without aura. Based on our experience with four such trials, we point to a number of possible solutions and outline areas for future inquiry. We make recommendations about subject selection; the choice, definition and assessment of outcome measures; optimal treatments in relation to aura and headache; and we provide samples of study report forms used to record occurrence of aura and headache in this population.