Hypothalamic Activation in Spontaneous Migraine Attacks

Marie Denuelle, MD; Nelly Fabre, MD; Pierre Payoux, MD; Francois Chollet, MD; Gilles Geraud, MD

Disclosures

Headache. 2007;47(10):1418-1426. 

In This Article

Methods

The local ethics committee approved the study.

Patients

Seven patients (6 females and 1 male, mean age: 38.1 years) were studied during a spontaneous, acute migraine attack. All of them fulfilled International Headache Society (IHS) criteria for episodic migraine without aura (ICHD-II code 1.1). None of the patients were undergoing prophylactic treatment. Other medications included the oral contraceptive pill in 4 of the subjects, and thyroxin therapy in 1 subject. All patients came in emergency in the PET center within 4 hours of the onset of migraine symptoms; they were also instructed not to take any triptan or analgesic. Before PET scanning, patients were asked to describe the type and location of their headache, as well as any associated symptoms such as nausea, photophobia, and phonophobia. A pregnancy test was performed in female subjects of childbearing age before each scan. Informed consent was obtained from each patient.

PET Scanning

Patients were scanned in 3 conditions (2 scans for each condition): (1) during migraine headache, (2) after headache relief following 6 mg sumatriptan s.c. injection, and (3) during an attack-free interval (15 to 60 days later) (Fig. 1). The time interval between conditions 1 and 2 (the latency of complete headache relief) varied from 20 to 120 minutes. At the end of each scan, the subjects were again asked to rate their headache using a scale from 0 to 10 (0 = no pain, and 10 = the most severe pain imaginable). We confirmed by phone that patients did not have headaches in the 48 hours before and after the attack-free scan.

Figure 1.

Study design.

Data Acquisition

To avoid visual and auditory stimulation, subjects wore opaque goggles while being scanned in a darkened, quiet room. Their head was immobilized, and head position was aligned transaxially to the orbitomeatal line with a laser beam and controlled before each acquisition. PET measurements were performed with a tomograph (EXACT-HR+; CTI-Siemens, Knoxville, TN, USA) that allowed the 3-dimensional acquisition of 63 transaxial slices. Spatial resolution was 4.5mmand 4.1mmin the transaxial and axial directions, respectively.Avenous cannula was inserted to administer tracer, ~350 mBq of H2 15O, in the left arm. The tracer was infused over 30 seconds at the rate of 6 mL/min. Integrated radioactivity counts were acquired in three 30-second frames beginning 5 to 15 seconds before the peak of the head curve. The interval between 2 scans for a same condition was 8 minutes. A transmission scan was obtained prior to the collection of the emission data for each study to correct for radiation attenuation by tissues in the head.

Data Analysis

Image analysis was performed using statistical parametric mapping (SPM2; WellcomeDepartment of Cognitive Neurology, London, UK, http://www.fil.ion.ucl.ac.uk/spm) implemented in MATLAB (Mathworks, Inc., Sherborn, MA, USA). Images of each subject were initially realigned with the reference to the first image to correct for motion artifact and then spatially normalized into a standard stereotaxic space defined by the atlas of Talairach and Tournoux. [7] The normalized images were smoothed with a Gaussian kernel of 8 mm full width at half maximum to account for intersubject differences in anatomy and allow valid statistical inference according to Gaussian random field theory. Statistical parametric maps were generated using an analysis of covariance model after normalization for global cerebral blood flow changes. Because migraine is often characterized by hemicrania, we mirrored the PET scans of the patients with left-sided headache in the sagittal plane. This allowed us to analyze all the patients (3 right hemicranias, 3 left hemicranias, and 1 bilateral headache) in the same analysis. Two comparisons were performed: comparison 1-rCBF during migraine headache versus rCBF during headache free interval; and comparison 2-rCBF after headache relief versus rCBF during headache free interval. All the conditions of activation were coded in order to be processed in SPM in blind condition to avoid a bias effect from the investigator. In accordance with previous studies,[2] we chose a threshold of P < .001 (uncorrected for multiple comparisons) and a cluster extent of >50 voxels for reporting. Our results survived a small volume correction using a 12-mm radius sphere at P < .05 centered on the midbrain, pons, and hypothalamus as reported in the Talairach atlas (respectively, midbrain x = 0, y = -25, z = -10; pons x = 0, y = -27, z = -28; hypothalamus x = 0, y = -2, z = -8).

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