What initiates a migraine attack? Conclusions from four longitudinal studies of quantitative EEG and steady-state visual-evoked potentials in migraineurs.

Acta Neurol Scand: 2011: 124 (Suppl. 191): 56–63. © 2011 John Wiley & Sons A/S.

Bjørk M, Stovner LJ, Hagen K, Sand T.

Objectives – Quantitative electroencephalograpic (QEEG) frequency spectra and steady-state visual-evoked potentials (SSVEP) are indicators of corticothalamic excitability (e.g., arousal). Increased interictal excitability is suggested to be an important element in the migraine pathophysiology. In this paper, we summarize our results from four studies of QEEG and SSVEP recordings in migraineurs interictally and in the days before an attack with the intention to shed light on attack-initiating mechanisms.

Material and methods – Thirty-two healthy controls, 33 migraineurs without and eight with aura each had three EEGs with photic stimulation on different days. Using the patient headache diaries, we classified the recordings as interictal, preictal, ictal, or post-ictal retrospectively. Interictal recordings were compared pairwise with attack-related EEGs from the same patient as well as with control EEGs. We also correlated clinical variables with the QEEG and SSVEP data.

Results – Between attacks, we found increased relative theta activity and attenuated medium-frequency photic responses in migraineurs without aura compared with those in controls. Within 36 h before the attack, slow and asymmetric EEG activity developed. Increased trigger sensitivity and photophobia correlated with higher theta power and depressed photic responses. Attack duration, migraine history duration, and pain intensity were associated with EEG slowing.

Conclusions – A general tendency toward EEG slowing and depression of photic responses characterized the migraine group. This pattern was also related to increased severity of symptoms. A change in cortical activity occurred within 36 h before attacks. Our results indicate that thalamocortical hypoexcitability is associated with attack initiation and sensory hypersensitivity in migraine.

What initiates a migraine attack? Conclusions from four longitudinal studies of quantitative EEG and steady-state visual-evoked potentials in migraineurs.

Acta Neurol Scand: 2011: 124 (Suppl. 191): 56–63. © 2011 John Wiley & Sons A/S.
Bjørk M, Stovner LJ, Hagen K, Sand T. 


Objectives – Quantitative electroencephalograpic (QEEG) frequency spectra and steady-state visual-evoked potentials (SSVEP) are indicators of corticothalamic excitability (e.g., arousal). Increased interictal excitability is suggested to be an important element in the migraine pathophysiology. In this paper, we summarize our results from four studies of QEEG and SSVEP recordings in migraineurs interictally and in the days before an attack with the intention to shed light on attack-initiating mechanisms.


Material and methods – Thirty-two healthy controls, 33 migraineurs without and eight with aura each had three EEGs with photic stimulation on different days. Using the patient headache diaries, we classified the recordings as interictal, preictal, ictal, or post-ictal retrospectively. Interictal recordings were compared pairwise with attack-related EEGs from the same patient as well as with control EEGs. We also correlated clinical variables with the QEEG and SSVEP data.


Results – Between attacks, we found increased relative theta activity and attenuated medium-frequency photic responses in migraineurs without aura compared with those in controls. Within 36 h before the attack, slow and asymmetric EEG activity developed. Increased trigger sensitivity and photophobia correlated with higher theta power and depressed photic responses. Attack duration, migraine history duration, and pain intensity were associated with EEG slowing.


Conclusions – A general tendency toward EEG slowing and depression of photic responses characterized the migraine group. This pattern was also related to increased severity of symptoms. A change in cortical activity occurred within 36 h before attacks. Our results indicate that thalamocortical hypoexcitability is associated with attack initiation and sensory hypersensitivity in migraine.

Migraine can be induced by sildenafil without changes in middle cerebral artery diameter

Migraine can be induced by sildenafil without changes in middle cerebral artery diameter

Brain, Vol. 126, No. 1, 241-247, January 2003© 2003 Guarantors of Brain doi: 10.1093/brain/awg009

Christina Kruuse, Lars Lykke Thomsen, Steffen Birk and Jes Olesen
Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, Copenhagen, Denmark
Correspondence to: C. Kruuse, MD, Department of Neurology, Glostrup Hospital, University of Copenhagen, DK-2600 Glostrup, Denmark E-mail: ckruuse@dadlnet.dk

Migraine is considered a neurovascular disease involving dilatation of cerebral arteries. Nitric oxide (NO) donors induce dilatation of cerebral and extracranial arteries and migraine, but NO has several mechanisms of action in addition to its cyclic guanosine monophosphate (cGMP)-mediated vasodilatation. We examined whether sildenafil (Viagra®), a selective inhibitor of cGMP-hydrolysing phosphodiesterase 5 (PDE5), which acts exclusively by increasing cGMP, can induce migraine and dilatation of cerebral arteries. We included 12 patients with migraine without aura in this double-blind, placebo-controlled crossover study, in which placebo or sildenafil 100 mg was administered orally on two separate days. Blood flow velocity in the middle cerebral artery (Vmca) was recorded by transcranial Doppler ultrasonography and regional cerebral blood flow in the territory of the middle cerebral artery (rCBFmca) was measured using SPECT (single photon emission computed tomography) and xenon 133 inhalation. Radial and temporal artery diameters were studied using high-frequency ultrasonography. Headache response, tenderness of pericranial muscles, blood pressure and heart rate were measured repeatedly. We found that migraine attack was induced by sildenafil in 10 of 12 migraine patients and by placebo in two of 12 patients (P = 0.01). Vmca (P = 0.1) and rCBFmca (P = 0.93) remained unchanged after sildenafil. Temporal (P = 0.47) and radial (P = 0.87) artery diameter and pericranial tenderness (P = 0.16) were unaffected by sildenafil. Systolic and diastolic blood pressures were unchanged but heart rate increased from a mean of 62 ± 2 to 74 ± 3 beats/min (P = 0.01) after sildenafil. Our results demonstrate that migraine may be induced via a cGMP-dependent mechanism, and we show for the first time that this occurs without initial dilatation of the middle cerebral artery.

We propose that triggering mechanisms may reside within the perivascular sensory nerve terminals or the brainstem. However, other sites of action may also be possible and future studies are needed to elucidate this. In the clinical use of sildenafil, patients who have migraine should be informed about the risk of migraine attacks.

The Mode of Action of Migraine Triggers: A Hypotheis

Lambert and Zagami has written a review article in "Headache" Feb 2009 edition.

It is on "The Mode of Action of Migraine Triggers: A Hypotheis"And the abstract says: Pain of migraine originates in the cortex, the immediate generator is in the brainstem.

Cortical activation induced by many different mechanisms often produce headache.

Normally there is a descending sensory inhibition from the brainstem. Triggers in most migraines produce excitation of cortical neurons. This causes withdrawal of descending sensory inhibition that originate in the brainstem.

Many brainstem nuclei seem to participate in the selective control of trigeminovascular sensation. This is through descending inhibitory mechanisms arising in the cortex. Peri-Aquiductal Gray matter and Nucleus Raphe Magnus are important here. Neurotransmitter 5-hydroxytryptamine is involved.

They summarize that cortical activation by migraine triggers (including cortical spreading depression) inhibits neuronal discharge in the brainstem. This facilitates trigeminovascular sensation.

Headache. 49(2):253-275, February 2009.Lambert, Geoffrey A. PhD; Zagami, Alessandro S. MBBS, MD