Neurol Sci (2008) 29:S44S46

DOI 10.1007/s10072-008-0885-6

HEADACHE CONTROVERSIES

Migraine with and without aura share the same pathogenic

mechanisms
R. Allan Purdy

Springer-Verlag 2008

Abstract Migraine with aura and without aura share the

same clinical features with respect to the headache, and differ nosologically in the presence or absence of aura. The
mechanisms of aura generation are now becoming clearer,
based on imaging studies, and a common migraine pathophysiology for all subtypes of migraine headaches now
seems reasonable, as it would seem implausible that all of
these neurological events have different pathogenic mechanisms. Both major subtypes of migraine clearly represent a
perturbation of normal physiology and employ normal
anatomic pathways to generate the aura and headache, similar to aura and a seizure. So what is the mechanism of
migraine aura? Do migraine without aura patients have clinically silent aura? Migraine is after all defined as a clinical
disorder and is the prototypic primary headache and thus its
uniform pathogenesis must underlie all that we know about
migraine clinically. This presentation will take the resolve
that the migraine with and without aura share the same
pathogenic mechanisms.

Migraine without aura is a common disorder, whereas

migraine with aura is less common but more dramatic in
that the neurological aura is what defines the headache.
In migraine without aura it is the headache features that
define the disorder [1]. In practice it is the visual aura,
usually a fortification spectra or scintillating scotomata
[2], which almost makes the diagnosis pathognomonic for
migraine with aura. Neurologists have always been interested in neurological symptoms, particularly aura as it
relates to migraine or epilepsy [3]. This issue of how the
aura is generated is now becoming clearer, based on
imaging studies but also the fact that the aura is linked to
the headache in some pathophysiological manner. It is
inconceivable to this author that migraine without aura,
which has identical clinical headache symptoms to

Keywords Migraine Aura Mechanisms Pathophysiology

R.A. Purdy ()
Department of Medicine
Dalhousie University
Halifax, Canada
e-mail: a.purdy@dal.ca

Fig. 1 Authors scintillating zig-zag bright light that moves across

visual field over some 20 minutes. On about half of the occasions
it is followed by migrainous headache, while the rest of the time,
no pain follows at all.

Neurol Sci (2008) 29:S44S46

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migraine with aura, can be generated in any other way

except by way of the same pathogenic mechanisms. In
fact patients can have migraine aura with headache and
without headache throughout their lives and particularly
later in life, as late life migraine accompaniments, and it
would seem implausible that all of these events have different pathogenic mechanisms (Fig. 1). It makes no sense
whatsoever clinically to suggest that the aura of migraine
should be disconnected from the actual headache any
more than the aura of epilepsy should be disconnected
from the actual seizure. Both disorders represent perturbations of normal physiology and employ normal
anatomic pathways to generate their neurological warnings prior to the generic event that defines the headache
or seizure.

the clinical evolution of migraine to also consider aura

as an integral part of the pathogenic mechanisms.
Also, a recent PET study showed that posterior cerebral hypoperfusion accompanying migraine auras could
also be present in migraine attacks without aura [18],
suggesting a common putative pathogenic mechanism for
migraine with aura.
This presentation will take the point of view in the
resolution that migraine with aura and migraine without
aura do share the same pathogenic mechanisms.
Migraine is a clinical disorder and current information
supports a common aetiopathogenesis for its various subtypes. Migraine is the prototypic primary headache disorder and thus its uniform pathogenesis must underlie all
that we know about migraine clinically.

What is the mechanism of migraine aura?

Acknowledgement Special thanks to Professor Peter Goadsby,

Department of Neurology, University of California, San Francisco,
CA, for providing some content material for this overview.

Aura is a clinical event in about 20% of migraine

patients, using IHS criteria [1]. Aura is typically visual
or sensory, and is accompanied by a spreading oligaemia
first reported by Olesen et al.s pioneering studies [4],
supported and extended by the work of the Boston Group
[5, 6]. The observation of an initial hyperaemic phase [7]
secures the validity of comparisons of migraine aura
with cortical spreading depression [8], however the
headache begins even while the oligaemia is still present
[9] and thus these aura studies show that headache is not
due to reactive vasodilatation as Wolff had considered
[10]. Also it appears that the cortical spreading depression of Leao [1113] has many similarities with aura,
and the human aura is the homologue of that process
observed in other species [14]. As only a small percentage of patients report aura, is it absent in most, or present but sub-clinical?
Fundamentally, migraine is an episodic headache
with certain associated features, in particular sensitivity
to light, sound and smells, as well as a neurological aura
in about one third of sufferers. These features give clues
to the pathophysiology of acute attacks, and any explanation must account for all of these cardinal features.

Do migraine without aura patients have clinically

silent aura?
Imaging data overwhelmingly report no change in brain
blood flow in migraine without aura [6, 15, 16], so it
seems unlikely that aura is unnoticed clinically. A case
of bilateral spreading oligaemia observed with positron
emission tomography (PET) [17] may support the presence of silent aura. This patient did not have typical
aura, but blurring, which is not uncommon in all types
of migraine. Thus is seems necessary when considering

References
1. Headache Classification Committee of The International
Headache Society (2004) The International Classification of
Headache Disorders (second edition). Cephalalgia 24[Suppl
1]:1160
2. Russell MB, Olesen J (1996) A nosographic analysis of the
migraine aura in a general population. Brain 119:355361
3. Gowers WR (1888) A manual of diseases of the nervous system. P. Blakiston, Son & Co, Philadelphia
4. Olesen J, Larsen B, Lauritzen M (1981) Focal hyperemia followed by spreading oligemia and impaired activation of rCBF
in classic migraine. Ann Neurol 9:344352
5. Cutrer FM, Sorensen AG, Weisskoff RM et al (1998)
Perfusion-weighted imaging defects during spontaneous
migrainous aura. Ann Neurol 43:2531
6. Sanchez del Rio M, Bakker D, Wu O et al (1999) Perfusion
weighted imaging during migraine: spontaneous visual aura
and headache. Cephalalgia 19:701707
7. Hadjikhani N, Sanchez del Rio M, Wu O et al (2001)
Mechanisms of migraine aura revealed by functional MRI in
human visual cortex. Proc Natl Acad Sci U S A 98:46874692
8. Lauritzen M (1994) Pathophysiology of the migraine aura. The
spreading depression theory. Brain 117:199210
9. Olesen J, Friberg L, Skyhoj-Olsen T et al (1990) Timing and
topography of cerebral blood flow, aura, and headache during
migraine attacks. Ann Neurol 28:791798
10. Wolff HG (1963) Headache and other head pain, 3rd Edn.
Oxford University Press, New York
11. Leao AAP (1944) Spreading depression of activity in cerebral
cortex. J Neurophysiol 7:359390
12. Leao AAP (1947) Further observations on the spreading
depression of activity in the cerebral cortex. J Neurophysiol
10:409414
13. Marshall WH (1959) Spreading cortical depression of Leao.
Physiol Rev 39:239288
14. Lauritzen M (2001) Cortical spreading depression in migraine.
Cephalalgia 21:757760
15. Olesen J (1991) Cerebral and extracranial circulatory disturbances in migraine: pathophysiological implications.

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Cerebrovasc Brain Metab Rev 3:128
16. Cohen AS, Goadsby PJ (2004) Functional neuroimaging of primary headache disorders. Curr Neurol Neurosci Rep 4:105110
17. Woods RP, Iacoboni M, Mazziotta JC (1994) Bilateral spread-

Neurol Sci (2008) 29:S44S46

ing cerebral hypoperfusion during spontaneous migraine
headache. N Engl J Med 331:16891692
18. Graud G, Denuelle M, Fabre N et al (2005) Positron emission
studies in migraine. Rev Neurol (Paris) 161:666670

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