P. Payoux

Photophobia in migraine: an interictal PET study of cortical hyperexcitability and its modulation by pain

Objective Photophobia is an abnormal sensitivity to light experienced by migraineurs and is perhaps caused by cortical hyperexcitability. In clinical studies, an inter-relation between light perception and trigeminal nociception has been demonstrated in migraineurs but not in controls. The purpose of the study was to verify this interaction by functional imaging. Methods The authors used H2O15 positron emitting tomography (PET) to study the cortical responses of seven migraineurs between attacks and the responses of seven matched control subjects to luminous stimulations at three luminance intensities: 0, 600 and 1800 Cd/m2. All three intensities were both with and without concomitant trigeminal pain stimulation. In order to facilitate habituation, the stimulations were started 30 s before PET acquisitions. Results When no concomitant pain stimulation was applied, luminous stimulations activated the visual cortex bilaterally in migraineurs (specifically in the cuneus, lingual gyrus and posterior cingulate cortex) but not in controls. Concomitant pain stimulation allowed visual cortex activation in control subjects and potentiated its activation in migraineurs. These activations by luminous stimulations were luminance-intensity-dependent in both groups. Concomitant stimulation by pain was associated with activation of the posterior parietal cortex (BA7) in migraineurs and controls. Interpretation The study shows the lack of habituation and/or cortical hyperexcitability to light in migraineurs. Moreover, the activation by light of several visual cortex areas (including the primary visual cortex) was potentiated by trigeminal pain, demonstrating multisensory integration in these areas.

Posterior cerebral hypoperfusion in migraine without aura

In cerebral blood flow studies, migraine aura is characterized by a posterior cortical hypoperfusion. In contrast, only rare and mild changes in brain perfusion have been demonstrated in migraine without aura, suggesting two different haemodynamic patterns in migraine with and without aura. Our aim was to study hypoperfusion with positron emission tomography (PET) as early as possible during spontaneous migraine without aura attacks. We used H2 15O PET to investigate seven patients (six female, one male) with migraine without aura (International Classification of Headache Diseases-II code 1.1) in three situations: during the headache phase, after headache relief following sumatriptan injection, and during an attack-free interval. Statistical analysis was performed with SPM2. Within 4 h after the attack onset, significant relative bilateral posterior cortical hypoperfusion was found and persisted after headache relief following sumatriptan injection. A posterior cortical hypoperfusion demonstrated in migraine without aura could suggest a common pathogenesis in migraine with and without aura. The significance of relative posterior hypoperfusion in migraine without aura is discussed according to the current knowledge of migraine pathogenesis.

Tomographie par émission de positons dans la migraine

Due to technical constraints and randomness of migraine attacks, studies using PET are scarce. Nevertheless, these studies have given new insights into migraine pathogenesis. One of the main facts revealed by PET studies is that posterior cerebral hypoperfusion accompanying migraine auras could also be present in migraine attacks without aura. This hypoperfusion is probably due to an increase of intrinsic vasoconstrictive tone in the cerebral circulation. Using PET within 6 hours after the onset of a spontaneous migraine attack, significant activations of brainstem (midbrain and pons) and of hypothalamus, persisting after headache relief by sumatriptan have been shown. These structures could play the role of migraine attack generators, modulating intrinsic vascular tone and central pain transmission.

The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader–Willi Syndrome

BACKGROUND AND OBJECTIVES: Patients with Prader–Willi syndrome (PWS) display poor feeding and social skills as infants and fewer hypothalamic oxytocin (OXT)-producing neurons were documented in adults. Animal data demonstrated that early treatment with OXT restores sucking after birth. Our aim is to reproduce these data in infants with PWS. METHODS: We conducted a phase 2 escalating dose study of a short course (7 days) of intranasal OXT administration. We enrolled 18 infants with PWS under 6 months old (6 infants in each step) who received 4 IU of OXT either every other day, daily, or twice daily. We investigated the tolerance and the effects on feeding and social skills and changes in circulating ghrelin and brain connectivity by functional MRI. RESULTS: No adverse events were reported. No dose effect was observed. Sucking assessed by the Neonatal Oral-Motor Scale was abnormal in all infants at baseline and normalized in 88% after treatment. The scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing significantly decreased from 16 to 9 (P < .001) and from 18 to 12.5 (P < .001), respectively. Significant improvements in Clinical Global Impression scale scores, social withdrawal behavior, and mother–infant interactions were observed. We documented a significant increase in acylated ghrelin and connectivity of the right superior orbitofrontal network that correlated with changes in sucking and behavior. CONCLUSIONS: OXT is well tolerated in infants with PWS and improves feeding and social skills. These results open perspectives for early treatment in neurodevelopment diseases with feeding problems.

Iterative three-dimensional expectation maximization restoration of single photon emission computed tomography images: application in striatal imaging.

Single photon emission computed tomography imaging suffers from poor spatial resolution and high statistical noise. Consequently, the contrast of small structures is reduced, the visual detection of defects is limited and precise quantification is difficult. To improve the contrast, it is possible to include the spatially variant point spread function of the detection system into the iterative reconstruction algorithm. This kind of method is well known to be effective, but time consuming. We have developed a faster method to account for the spatial resolution loss in three dimensions, based on a postreconstruction restoration method. The method uses two steps. First, a noncorrected iterative ordered subsets expectation maximization (OSEM) reconstruction is performed and, in the second step, a three-dimensional (3D) iterative maximum likelihood expectation maximization (ML-EM) a posteriori spatial restoration of the reconstructed volume is done. In this paper, we compare to the standard OSEM-3D method, in three studies (two in simulation and one from experimental data). In the two first studies, contrast, noise, and visual detection of defects are studied. In the third study, a quantitative analysis is performed from data obtained with an anthropomorphic striatal phantom filled with 123-I. From the simulations, we demonstrate that contrast as a function of noise and lesion detectability are very similar for both OSEM-3D and OSEM-R methods. In the experimental study, we obtained very similar values of activity-quantification ratios for different regions in the brain. The advantage of OSEM-R compared to OSEM-3D is a substantial gain of processing time. This gain depends on several factors. In a typical situation, for a 128 x 128 acquisition of 120 projections, OSEM-R is 13 or 25 times faster than OSEM-3D, depending on the calculation method used in the iterative restoration. In this paper, the OSEM-R method is tested with the approximation of depth independent resolution. For the striatum this approximation is appropriate, but for other clinical situations we will need to include a spatially varying response. Such a response is already included in OSEM-3D.

Relationship of brain β-amyloid to gait speed

mutation. Methods: Twelve GSS F198S mutation carriers and ten NCs were imaged using [F]FDG PET with standard techniques. A static 30-60 minute image was created and normalized to a pons reference region to create an SUVR image for each participant. These SUVR images were then assessed on a voxel-wise basis for the effect of clinical diagnosis and mutation carrier status. Voxel-based analyses were covaried for age and gender. Findings were displayed at a voxel-wise threshold of p<0.01 (uncorrected) and minimum cluster size (k) 1⁄4 50 voxels. SPM8 was used for all pre-processing and voxel-wise statistical analyses. Results: At the time of the scan, seven GSS F198S mutation carriers were symptomatic (SC), showing signs of motor and cognitive impairment or dementia, and five GSS F198S mutation carriers were asymptomatic (AC). All NCs showed no cognitive impairment. SCs showed lower glucose metabolism in the left striatum compared to ACs and NCs, and bilaterally in the cerebellum compared to NCs (Fig. 1A-C). ACs showed hypometabolism in the right cerebellum compared to NCs (Fig. 1D).Conclusions:These findings suggest that hypometabolism in the cerebellar and striatal regions may partially underlie motor and cognitive dysfunction in GSS F198S patients.