1. THE EXTRACRANIAL ARTERIES AND MIGRAINE

2. by arterial dilatation
Migraine is caused
by arterial dilatation 2

3. EXTRACRANIAL VASODILATATION and migraine PAIN3

4. AN ARTIFICIAL CONTROVERSY4

5. HOW COULD THIS HAPPEN ?

6. WE TEND TO FALL IN LOVE WITH THEORIES, AND THEN WE TWIST THE FACTS TO SUIT OUR THEORIES – INSTEAD OF THEORIES TO SUIT THE FACTS

7. WE DON’T CHECK REFERENCES !

8. THE EXTRACRANIAL ARTERIES

9. Harold Wolff Jes Olesen Guus Schoonman Peter Goadsby
THE MAIN PLAYERS
Harold Wolff
Jes Olesen
Guus Schoonman
Peter Goadsby

10. WOLFF GOADSBY

11. ANTI-WOLFF LOBBY

12. WOLFF’s VASCULAR THEORY
Intracranial vasospasm causes CSD
Extracranial vasodilatation plays a part in migraine pain

13. JES OLESEN
The pattern of spread of CSD does not correlate with the vascular boundaries of the major cerebral vessels
Olesen J, Larsen Bo, Lauritzen M. Focal Hyperemia Followed by Spreading Oligaemia and
impaired Activation of rCBF in Classic Migraine. Ann. Neurol. 1981; 9:

14. WOLFF’s VASCULAR THEORY – part one
Intracranial vasospasm causes CSD

15. WOLFF’s VASCULAR THEORY – part two
Extracranial vasodilatation
plays a part in migraine
pain

16. Occipital
Artery
Superficial
Temporal
Artery

17. rCBF changes do not correlate with the painful phase of migraine
JES OLESEN
rCBF changes do not correlate with the painful phase of migraine
Olesen J, et al. Timing and Topography of Cerebral Blood Flow, Aura, and Headache
during Migraine Attacks. Ann. Neurol. 1990; 28: 17

18. “The vascular theory of migraine – a great story wrecked by the facts”
Goadsby P. Brain 2009; 132: 6-7

19. Olesen proved that vascular to the painful phase of migraine
changes are UNRELATED
to the painful phase of migraine
Goadsby P. The vascular theory of migraine
– a great story wrecked by the facts. Brain 2009;
132: 6-7 19

20. WHERE IS THE LOGIC ? WOLFF OLESEN Parietal branch Frontal branch STA
OCCIPITAL
WOLFF OLESEN 20

21. ANTI-
WOLFF
LOBBY

22. ”During migraine, blood vessel diameters were no different from
baseline, nor between headache
and non-headache sides”.
Schoonman et al. Migraine headache is not associated with cerebral or
meningeal dilatation – a 3T magnetic resonance angiographic study.
Brain 2008 Aug;131:

23. ECA
ECA

24. SCHOONMAN et al did NOT study the
EXTRACRANIAL TERMINAL
BRANCHES of the
External Carotid Artery

25. Migraine occurs without any change in intracranial or
EXTRACRANIAL
vessels
Goadsby P. The vascular theory of migraine – a great story
wrecked by The facts. Brain 2009; 132: 6-7

26. WHERE IS THE LOGIC ? ECA ECA WOLFF SCHOONMAN Parietal branch Frontal
STA
OCCIPITAL
WOLFF SCHOONMAN 26

27. ANTI-
WOLFF
LOBBY

28. THE EVIDENCE 1-13

29. 1. EXTRACRANIAL ARTERIAL OCCLUSION
Migraine pain is often relieved by:
Digital arterial compression
Temporal artery massage
Application of a tight headband
Louis S. A bedside test for determining types of vascular headache. Headache. 1981; 21:87-8.
Blau JN, Dexter SL. The site of pain origin during migraine attacks. Cephalalgia 1981;1(3):
Drummond PD, Lance JW. Extracranial vascular changes and the source of pain in migraine headache.
Ann Neurol Jan;13(1):32-7.
Lipton SA. Prevention of Classic Migraine Headache by Digital Massage of the Superficial Temporal
Arteries. Ann. Neurol. 1986; 19:
Shevel EJ, Spierings E. The Role of the Extracranial Arteries in Migraine. Cranio 2004; 22:
Vijayan N. Head band for migraine headache relief. Headache. 1993; 33:
Blau JN, Dexter SL. The site of pain origin during migraine attacks. Cephalalgia. 1981; 1:

30. significantly larger on the painful side than on the
2. LUMINAL DIAMETER
TEMPORAL ARTERIES are
significantly larger on the
painful side than on the
non-painful side
Iversen HK, Nielsen TH, Olesen J, Tfelt-Hansen P. Arterial responses during migraine headache.
Lancet. 1990; 336:

31. Self-regulation of the TEMPORAL ARTERY is effective in reducing
3 .BIOFEEDBACK
Self-regulation of the TEMPORAL
ARTERY is effective in reducing
migraine pain
Farmer K. Biofeedback and the Treatment of Headache. In: Cady RK, Fox AW, editors.
Treating the Headache Patient. New York: Marcel Dekker, Inc; 1995;
Lisspers J, Oost LG. BVP-biofeedback in the treatment of migraine. The effects of
constriction and dilatation during different phases of the migraine attack. Behav
Modif Apr;14(2):

32. 4. FUNCTIONAL NEUROIMAGING
Functional neuroimaging shows that
EXTRACRANIAL blood flow increases
during migraine, subsiding as the
pain subsides
Sakai F. Meyer JS. Regional cerebral hemodynamics during migraine and cluster headaches
measured by the 133Xe inhalation method. Headache. 1978; Jul;18(3):
Elkind, A. H., Friedman, A. P., and Grossman, J.: Cutaneous blood flow in vascular headache of
the migraine type, Neurology. (Minn.) 1964; 14: 24.
Sakai F, Meyer JS. Abnormal cerebrovascular activity in patients with migraine and cluster
headache. Headache. 1979: 19;

33. 5. TRIGEMINAL GANGLION STIMULATION
causes a substantial elevation of
EXTRACRANIAL levels of CGRP
Goadsby PJ, Edvinsson L, Ekman R. Release of vasoactive peptides in the
extracerebral circulation of humans and the cat during activation of the trigeminovascular
system. Ann. Neurol Feb;23(2):193-6.

34. Trigeminal Ganglion Stimulation
OWN GOAL 34

35. Potent vasodilator of human TEMPORAL arteries
6. CGRP
Potent vasodilator of human TEMPORAL arteries
Olesen et al. The peptidergic innervation of the human superficial temporal artery: immunochemistry, ultrastructure, and vasomotility. Peptides 1995; 16: 35

36. 7. CGRP CGRP levels are substantially increased in
the EXTERNAL jugular during migraine
Goadsby, P. J, Edvinsson L., et al. (1990). "Vasoactive peptide release in the
extracerebral circulation of humans during migraine headache." Ann Neurol 28(2):
Goadsby, P. J., Edvinsson L. The trigeminovascular system and migraine: studies
characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann
Neurol 1993; 33: 48-56

37. CGRP increased in the EXTERNAL jugular
OWN GOAL
NO 2 37

38. 8. CGRP Relief of migraine pain coincides with reduced CGRP in
the EXTRACRANIAL blood
Goadsby PJ, Edvinsson L. Neuropeptides in migraine and cluster headache.
Cephalalgia Oct;14(5):320-7.

39. Migraine pain and EXTRACRANIAL CGRP decrease simultaneously
OWN GOAL
NO 3 39

40. Ergots Triptans BIBN4096BS
Let us now look at the pharmacological evidence – the actions of these widely used migraine rescue drugs
the ergots and the the triptans,
and
BIBN4096BS, one of the gepants, which as you know appear to be the most promising next generation of migraine-specific drugs.

41. the EXTRACRANIAL arteries
9. ERGOTAMINE & DHE
Strongly constrict
the EXTRACRANIAL arteries
Graham JR, Wolff HG. Mechanism of migraine headache and action of ergotamine tartrate. Arch. Neurol. Psychiat. 1938; 39:
Brazil P, Friedman AP. Craniovascular studies in headache; a report and analysis of pulse volume tracings. Neurology Feb;6(2):

42. 10. Simultaneously reduce amplitude of pulsation
migraine pain and the
amplitude of pulsation
of the SUPERFICIAL
TEMPORAL ARTERIES
Graham JR, Wolff HG. Mechanism of migraine headache and action of ergotamine tartrate.
Arch. Neurol. Psychiat. 1938; 39:
Brazil P, Friedman AP. Craniovascular studies in headache; a report and analysis of pulse
volume tracings. Neurology Feb;6(2):

43. Triptans affect neuronal transmission in
the brain
Goadsby P. The vascular theory of migraine – a great story wrecked by the
facts. Brain 2009; 132: 6-7

44. Sumatriptan does not affect the brain
unless the permeability of the BBB is
first ARTIFICIALLY INCREASED
Kaube H, Hoskin KL, Goadsby PJ. Inhibition by sumatriptan of central trigeminal neurones
only after blood-brain barrier disruption. Br J Pharmacol 1993; 109: 44

45. Triptans affect neuronal transmission in the brain
IS THIS LOGICAL ?
Sumatriptan does
NOT affect the brain
unless the
permeability of the
BBB is first
ARTIFICIALLY
INCREASED
Triptans affect neuronal transmission in the brain
GOADSBY GOADSBY

46. ANTI-
WOLFF
LOBBY

47. Potently constrict HUMAN TEMPORAL ARTERIES
11. TRIPTANS
Potently constrict HUMAN TEMPORAL ARTERIES
Jansen, I, Edvinsson L, et al. "Sumatriptan is a potent vasoconstrictor of human dural arteries
via a 5-HT1-like receptor.“ Cephalalgia 1992; 12(4):
Edvinsson L, Jansen I, Olesen J. Chracterization of human cranio -vascular 5HT receptors. In:
Olesen J, Saxena P. ed International Headache Research Seminars. New York: Raven Press, 1982.

48. 12. TRIPTANS Relief of migraine pain with triptans
coincides with reduction of CRGP
in the EXTRACRANIAL blood.
Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies
characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann
Neurol Jan;33(1):48-56.

49. TRIPTANS relieve migraine pain while reducing CRGP in the
EXTRACRANIAL blood
OWN GOAL
NO 4 49

50. BIBN4096BS Was developed specifically to reverse
the VASODILATATION caused
by the increased CGRP levels
during migraine
Doods H. CGRP antagonists: unravelling the role of CGRP in migraine. Trends in pharmacological sciences 2007; 28:

51. 13. BIBN4096BS ARTERY Is strongly vasoactive and completely
inhibits CGRP-induced dilatation of
the SUPERFICIAL TEMPORAL
ARTERY
Petersen KA, Lassen LH, Birk S, Lesko L, Olesen J. BIBN4096BS antagonizes human alpha-CGRP-
induced headache and extracerebral artery dilatation. Clin Pharmacol Ther 2005b; 77:
Verheggen, R., K. Bumann, et al. (2002). "BIBN4096BS is a potent competitive antagonist of the
relaxant effects of alpha-CGRP on human temporal artery: comparison with CGRP(8-37)." Br J
Pharmacol 136(1):

52. Wishful = thinking IS THIS LOGICAL ? GOADSBY PETERSEN
BIBN4096BS is “without
vascular effects”
and
“constriction is not required
since dilatation is not a part
of the process”
Goadsby, PJ. The vascular theory of
Migraine – a great story wrecked by the facts. Brain
2009; 132: 6-7
BIBN4096BS is strongly
vasoactive and completely
inhibits CGRP-induced
dilatation of the superficial
temporal artery
Petersen KA et al BIBN4096BS antagonizes
human alpha-CGRP-induced headache and
extracerebral artery dilatation. Clin Pharmacol
Ther 2005b; 77:
Wishful
thinking =
GOADSBY
PETERSEN

53. ANTI-
WOLFF
LOBBY

54. AN IMPENETRABLE WALL OF DENIAL
WISHFUL
THINKING
SUPPRESSED FACTS
INCORRECT
REFERENCES
UNPROVEN
THEORIES AN
IMPENETRABLE
WALL
OF DENIAL
BLUSTER
DATA
MANIPULATION
OBFUSCATION
HUBRIS
ANIMAL
STUDIES
TUNNEL
VISION
VESTED
INTERESTS
MISQUOTES

55. The American Headache Society has
specifically excluded Wolff’s vascular
theory from the curriculum for American
medical students
Young WB, Rosen N, Sheftell F. Square One: Headache Education for the Medical Student.
Headache 2007; 47:

57. ERASED FROM HIS OWN BOOK !

58. NO-ONE
HAS BEEN LISTENING

59. CONFIRMED by the FACTS WOLFF’S VASCULAR THEORY of migraine – is
not a great story
WRECKED
by the facts
a great story
CONFIRMED
by the FACTS

60. WOLFF’S THEORY OF EXTRACRANIAL VASODILATATION

61. 61