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

Abstract and Introduction

Abstract

Background: Migraine sufferers experience premonitory symptoms which suggest that primary hypothalamic dysfunction is a likely trigger of the attacks. Neuroendocrine and laboratory data also support this hypothesis. To date, positron emission tomography (PET) scans of migraine sufferers have demonstrated activation of brainstem nuclei, but not of the hypothalamus.
Objective: To record cerebral activations with H2 15O PET during spontaneous migraine without aura attacks.
Methods: We scanned 7 patients with migraine without aura (6 females and 1 male) in each of 3 situations: within 4 hours of headache onset, after headache relief by sumatriptan injection (between the fourth and the sixth hour after headache onset), and during an attack-free period.
Results: During the headache we found not only significant activations in the midbrain and pons, but also in the hypothalamus, all persisting after headache relief by sumatriptan.
Conclusion: Hypothalamic activity, long suspected by clinical and experimental arguments as a possible trigger for migraine, is demonstrated for the first time during spontaneous attacks.

Introduction

Functional imaging with positron emission tomography (PET) or functional MRI (fMRI) has led to a reappraisal of the pathophysiology of primary headaches, particularly in migraine and cluster headache. The main difficulty with functional imaging in an episodic disorder is to capture rare, spontaneous attacks when the imaging techniques require considerable planning. This situation explains the scarcity of functional imaging during spontaneous attacks of migraine. There are only 2 PET studies of spontaneous migraine attacks. Weiller and colleagues scanned 9 subjects with right-sided migraine without aura within 6 hours of the onset of spontaneous migraine headache and after treatment with sumatriptan.[1] The study showed brainstem activation during migraine that persisted after sumatriptan injection and headache resolution. Recently, Afridi and colleagues also found brainstem activation in 5 patients scanned within 24 hours of onset of migraine. Two of the patients in this study had auras before the headache.[2]

In other studies, migraine headaches were provoked. Twenty-four subjects were studied with PET from the earliest point of a migraine headaches induced with intravenous glyceryl trinitrate.[3] Activation of dorsolateral pontine nuclei ipsilateral to the headache symptoms were observed. In a BOLD functional MRI study,[4] the purpose was to investigate activation of brainstem structures in patients with visually triggered migraine. Twenty-six patients with migraine (23 with aura and 3 without aura) were studied during repeated checkerboard visual stimulation. An activation of the red nucleus and substantia nigra was found.

The fact that migraine headaches begin and end seemingly spontaneously suggests an as-yet-determined trigger. On the basis of functional imaging studies of migraineurs, a role for central brainstem structures as primary "generators" of migraine headaches was proposed.[1,5] Migraine could be caused by episodic dysfunction of those brainstem nuclei that activate a network of cortical and subcortical structures that modulate nociceptive function and vascular control. However, many migraine patients experience before an attack premonitory autonomic and endocrine symptoms (sleep disturbances, changes of wakefulness and alertness, as well as changes of appetite and thirst) that may well be attributed to primary hypothalamic dysfunction.[6] Hypothalamus and interconnected brainstem area could play a key role in migraine physiopathology.

By detecting increases in the regional cerebral blood flow (rCBF) in H2 15O PET, our study sought to determine which brain structures were activated during spontaneous attacks of migraine without aura. The results replicate the brainstem activation found previously and, for the first time, demonstrate activation of the hypothalamus during migraine headaches. This latter finding modifies the current conception of primary headaches.

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