Neurology -- Correspondence for Vanmolkot et al., 0 (2007) 10000260

Correspondence published:

Altered arterial function in migraine of recent onset: Steven R Brenner, None (2 August 2007)

Altered arterial function in migraine of recent onset: David S. Summers, (no other authors) (2 August 2007)

Reply from the authors: Jan N de Hoon, Floris Vanmolkot (2 August 2007)

Altered arterial function in migraine of recent onset 2 August 2007

Steven R Brenner,
Departments of Neurology at the St. Louis VA Medical Center and St. Louis University Medical Center
Dept's Neurology, JC 127, St. Louis VA Medical Center, 915 North Grand, St. Louis, Mo 16106,
None
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Re: Altered arterial function in migraine of recent onset

SBren20979{at}aol.com Steven R Brenner, et al.

I read the article by Vanmolkot et al with interest. [1] Plasma cytokines such as Il-10, TNFalpha and Il-1 beta are elevated in patients during migraine attacks, probably in response to vasoactive peptides such as calcitonin gene-related peptide released from primary afferent neurons in the trigemino-vascular circulation in migraine headache. [2]
A high prevalence of patent foramen ovale has been reported in patients who experience migraine with aura, with an odds ratio of 2.92 for patent foramen ovale in such patients compared to a normal population. [3] The large proportion of patients experiencing migraine with aura in Vanmolkot’s study [1] may have contained a larger proportion of patients with patent foramen ovale or arteriovenous shunts than is usually seen in the general population.
Arteriovenous shunting of vasoactive substances from the venous to the arterial system through a patent foramen ovale in migraine patients may affect endothelial function causing altered functional arterial properties such as decreased arterial compliance, as was seen in Vanmolkot’s study. [1]
Impaired endothelial function could lead to vascular complications of migraine such as stroke.
References
1. Vanmolkot F, Van Bartel L, de Hoon J. Altered arterial function in migraine of recent onset. Neurology 2007; 68: 1563-1570.
2. Perini F, D’Andrea G, Galioni E, et al. Headache 2005; 45: 926- 931.
3. Ferrarini G, Malferrari G, Zucco R, et al. High prevalence of patent foramen in migraine with aura. J Headache pain. 2005; 6: 71-76.
Disclosure: The author reports no conflicts of interest.

Altered arterial function in migraine of recent onset 2 August 2007

David S. Summers,
Retired neurologist (U. of UT Medical Center, 1972-76)
1520 Pasadena Dr. Erie, PA 16505,
(no other authors)
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Re: Altered arterial function in migraine of recent onset

dssmd{at}earthlink.net David S. Summers, et al.

The vascular mechanism for migraine as confirmed by Vanmolkot et al [1] and discussed by Tietjen under "migraine as a systemic disorder" is interesting. [4]
In 1977, I hypothesized that lateralization of migraine could result from localized vascular changes in the hemicranium and in the ipsilateral retina, trunk and limbs possibly with an adrenergic mechanism. [5] The anatomical separation of sympathetic ganglia from their paired components of the opposite side was regarded as a plausible explanation of hemicrania having ipsilateral, retinal, sensory, and motor symptoms.
My hypothesis also suggested that hemicrania with ipsilateral symptoms may have a peripheral, vascular mechanism as opposed to "hemiplegic migraine" where the sensory, motor or visual symptoms of which may be attributed to contralateral brain pathology until proven otherwise.
Among 110 migraineurs in my analysis, 53 (47.7%) had ipsilateral symptoms but only 4 (3.6%) had sensorimotor or visual symptoms contralateral to the side of head pain. Thus, the history alone may indicate a peripheral, vascular, non-pyramidal, non-lemniscal mechanism for hemicrania when ipsilateral symptoms occur. These would obviate a need for cerebral CT, MRI, angiography or other forms of brain imaging. The evidence of altered vascular function among the Vanmolkot cases appears to support an ipsilateral, vascular and possibly adrenergic mechanism for migraineurs with hemicrania and ipsilateral symptoms.
Yamamoto and Meyer were among the earliest investigators to document malfunction of vasomotor adrenoreceptors in hemicrania including cluster headache [6] but they and others omitted a reference to my hypothesis. [7]
Migraine remains a protean, systemic malady but newer avenues of investigation promise improved management and prevention of migraine, stroke and possibly other forms of vasculopathy.
References
4. Tietjen GE. Migraine as a systemic disorder. Neurology 2007;68:1555-1556.
5. Summers DS. Hypothesis: Hemicrania and ipsilateral trunk & limb symptoms. Headache 1977;17:219-221.
6. Yamamoto M, Meyer JS. Hemicranial disorder of vasomotor adrenoceptors in migraine & cluster headache. Headache 1980;20:321-335.
7. Raskin N. Conclusions: Advances in the pharmacology of headache. Headache 1990;30:4-28 (Suppl. to number 1).
Disclosure: The author reports no conflicts of interest.

Reply from the authors 2 August 2007

Jan N de Hoon,
Center for Clinical Pharmacology, University Hospital Gasthuisberg (K.U.Leuven)
Herestraat 49, 3000 Leuven, Belgium,
Floris Vanmolkot
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Re: Reply from the authors

jan.dehoon{at}uz.kuleuven.ac.be Jan N de Hoon, et al.

Dr. Brenner proposes an interesting theory linking migraine and altered arterial function through right-to-left shunts (RLS). According to this theory, arterial dysfunction in patients with migraine with aura is caused by circulating vasoactive substances that are shunted from the venous to the arterial circulation and therefore not filtered by the lungs. To confirm this theory at least two lines of evidence are needed which are currently lacking in the medical literature.
First, the presence of arterial dysfunction needs to be confirmed in patients with RLS. Second, shunting of vasoactive substances, (e.g., endothelin-1) should be shown in patients with RLS. Unfortunately, we did not assess the presence of patent foramen ovale in our cross-sectional study. In addition, our study was not powered to compare arterial function between migraine patients with and without aura.
A recent study in a population of migraine patients without aura showed a decreased brachial artery flow-mediated dilation. [7] This finding implies that RLS is not the sole factor mediating altered arterial function in migraine, as migraine without aura is not associated with RLS.
Dr. Summers hypothesized that the lateralization of symptoms in migraine may be due to unilateral vascular changes, possibly by an adrenergic mechanism. One explanation for the increase in arterial tone in migraineurs, as suggested by our findings, may be autonomic nervous system (ANS) dysfunction. ANS dysfunction has been previously observed in migraineurs. [8]. Unfortunately, autonomic function was not assessed in our study.
In addition, we did not assess arterial structure and function bilaterally. Hence, we could not assess correlation between: autonomic function and arterial function; and lateralization of symptoms and possible lateralization of alterations in arterial function. As mentioned in our discussion, we urge caution in concluding that our study “confirms a vascular mechanism for migraine”, as the design of the study was cross-sectional.
We cannot exclude that migraine and arterial abnormalities share a common cause or that these abnormalities are the consequence of multiple migraine attacks. Furthermore, we assessed arterial function interictally and therefore do not know whether changes in arterial function occur in the hours leading up to a migraine attack.
References
7. Yetkin E, Ozisik H, Ozcan C, Aksoy Y, Turhan H. Decreased endothelium-dependent vasodilatation in patients with migraine: a new aspect to vascular pathophysiology of migraine. Coronary Artery Disease 2006;17:29-33.
8. Shechter A, Stewart WF, Silberstein SD, Lipton RB. Migraine and autonomic nervous system function: A population-based, case-control study. Neurology 2002;58:422-427.
Disclosure: The authors report no conflicts of interest.