From the archived Special Topic of
Migraine & Other Vascular
Migraine is a form of neurovascular headache in
which the brainstem structures that mediate pain are
disinhibited, and vessels in the dura and the head
dilate, stretching the nerves around the artery,
thereby stimulating them into releasing chemicals that
cause inflammation and pain. Migraine affects about 8%
of the adult population; females are twice as likely as
males to suffer an attack. The symptoms are a severe
throbbing head pain, mostly one sided, with
deterioration in physical activity. These effects are
According to our Special Topics analysis of migraine research, Professor
Hans-Christoph Diener ranks at #8, with 110 papers cited a total of 1,329
times. One of these papers, "Guidelines for controlled trials of drugs in
migraine: Second edition," (Tfelt-Hansen P, et al., Cephalalgia
20: 765-86, November 2000), is ranked at #9 on our list of the
most-cited papers in the past decade. Four other papers of Professor
Diener's are on the list of the top 20 papers published in the past two
Science IndicatorsSM from
Professor Diener's work includes 158 papers cited a total of 3,024 times in
the field of Neuroscience & Behavior and 222 papers cited a total of
2,650 times in the field of Clinical Medicine.
Professor Diener is the chairman of the Department of Neurology at the
University of Essen in Germany.
In the interview below, he talks with
ScienceWatch.com correspondent Simon Mitton about his
research on the neurology of acute migraine.
How did you become interested in headache
I did my medical training at the Albrecht-Ludwigs-Universität in
Freiburg. From 1970 to 1975, I studied in both the faculty of philosophy
and the medical school, where I studied basic neurophysiology,
neuropsychology, and psychophysics. Then I started to work in psychophysics
and cerebellar physiology. Finally I went to the University of
Tübingen where I finished my neurology training and got my Ph.D. in
While I was there I got interested in headache. My chairman told me I
should keep my fingers off headache because it has nothing to do with
science! Nevertheless I started to work on medication overuse in headache.
Then when I moved to Essen as professor of neurology in 1989 (that's when I
became chairman here) I established a headache research group. We soon
started animal experiments as a platform for neurological studies and we
did all kinds of clinical trials.
Now I am the head of the German Headache Network, a collaboration which has
14 centers attached and is funded by the German Ministry of Education and
In your career you have demonstrated a deep interest in
a wide range of subjects. You have worked on cerebrovascular diseases,
cerebellar disorders affecting the motor system, and headache. In the
latter case, can you indicate your general areas of interest?
I have worked on the mechanisms and therapies of drug-induced headache. To
some extent I have specialized in the action of migraine drugs, with some
emphasis on clinical efficiency as determined from trials. I have been
interested in the prophylactic action of beta-blockers and calcium channel
antagonists in migraine. I have also worked with animal models for
migraine, to investigate the role of cerebral vessels and neurogenic
Could you tell me about the patient care and research
environments in which you work?
Our inpatient department has 53 beds and a stroke unit with six beds. In
company with the Clinic of Internal Medicine, we have an intensive care
unit with 17 beds. Our physicians, nurses, therapists, psychologists, and
social workers provide patient care. We have a large number of technical
procedures available in our department
There are 11 research groups. A number of clinical studies are coordinated
and executed at our Department. Our research contributes to provide the
highest standard of patient care with evidence-based therapies.
How large is the network you are chairing?
The funding is 1.8 million euros ($2.6 million) per year. Eight of the 14
groups are here in Essen, and the remainder are in Berlin, Hamburg,
Erlangen, Mainz, Aachen, and Munich. We cover everything from basic
research with animals, epidemiology, and through to therapy studies.
How does the group compare to other European centers? It
must be one of the largest.
No other institution is funded or functions in the way we do. So in that
sense we are unique in Europe. There was recently a publication in the
journal Cephalalgia about the funding of headache research in
Europe. From that survey you can see that the highest spending is in
Germany, and most of that funding is coming to our institute.
In this analysis covering your papers published since
January 1997, your most-cited publication is a set of guidelines for
controlled trials of drugs in migraine. Why has this second edition of
recommended procedures made such an impact?
The purpose of having a set of guidelines is to create a level playing
field so that from the point of view of medical science we can compare the
results from different trials with confidence. That principle applies
across the whole of biomedical research.
Everyone who does a clinical trial in migraine has to follow the guidelines
we published. That is why it is so frequently cited. The first and second
editions were the initiative of the International Headache Society Clinical
Trials Subcommittee. The guidelines include the procedures to be followed
for trial design, and the primary and secondary endpoints. They were
adopted by EMEA, the European agency for approval of new drugs. The
recommendations from EMEA are basically identical to those in the
Is there an international dimension to these
Yes, indeed there is. The guidelines were developed because of a need "to
improve the quality of controlled clinical trials in migraine," and because
only quality trials can form the basis for international collaboration on
With the current trend for huge multinational trials, there is a need for
increased awareness amongst clinical investigators of methodological issues
in clinical trials of drugs in migraine. These guidelines deal with those
specific for this illness.
Ranked at #2 in your list of papers from this survey is
a paper on drug efficacy (Tfelt-Hansen P, et al., "Ergotamine
in the acute treatment of migraine—a review and European
consensus," Brain 123: 9-18, 2000) one of your
specializations. This review examines ergotamine in the acute
treatment of migraine. What was learned in this review of
Ergotamine has been used in clinical practice for the acute treatment of
migraine for almost 80 years, but there has been little agreement on its
place in clinical practice. For this paper we worked as an expert group
from Europe to review the pre-clinical and clinical data on ergotamine as
it relates to the treatment of migraine. This is a review paper where we
basically argued that evidence for the efficacy of ergotamine is not very
The paper is highly cited because it gives specific suggestions for the
appropriate use of ergotamine. In essence, ergotamine, from a medical
perspective, is the drug of choice in a limited number of migraine
sufferers who have infrequent or long-duration headaches and are likely to
comply with dosing restrictions. But the review shows that for most
migraine sufferers requiring a specific anti-migraine treatment, a triptan
is generally a better option from both an efficacy and side-effect
Ranked at #3 on your list is a paper on topiramate and
the beta-blocker propranolol in migraine prophylaxis (Diner HC, et
al., "Topiramate in migraine prophylaxis—results from a
placebo-controlled trial with propranolol as an active control,"
J. Neurol. 251: 943-50, 2004). What's the story
The mode of action for most drugs used in migraine prophylaxis is unknown.
In addition, a powerful placebo effect exists in migraine prophylaxis
studies. When we did this study the most frequently used drugs for migraine
prophylaxis were beta-blockers, anticonvulsants, serotonin antagonists, and
calcium channel blockers. The efficacy of these drugs is at best 50%, and
in addition they have side effects that may be unacceptable to some
patients. Therefore, the search for further prophylactics for migraine was
the driver behind this paper.
Why did topiramate in particular attract your
In July 1995, topiramate received approval in the UK as adjunctive therapy
for the treatment of partial-onset seizures in adults. Topiramate is
currently approved as a monotherapy for epilepsy in more than 40 countries.
Its action on neurotransmitters suggested that it might be an effective
compound for controlling the frequency of migraine attacks.
We conducted a randomized, double-blind, multicenter trial to evaluate the
efficacy and safety of topiramate versus placebo for migraine prophylaxis
with propranolol as an active control. The outcome was that we demonstrated
that topiramate has about the same efficacy as propranolol. But, and this
is important in terms of citations, we added a new drug to the toolkit
available for the treatment of migraine.
Neurology is the focus of paper #4 (Kaube H, et
al., "Acute migraine headache—possible sensitization of
neurons in the spinal trigeminal nucleus?" Neurology 58:
1234-8, 2002). What is the main result in this contribution?
That paper reports an investigation, using a novel blink reflex, of 17
migraine patients within six hours of an acute one-sided attack. Our result
suggested that during a migraine attack the central trigeminal neurons are
Paper #5 (Katsarava Z, et al., "Incidence and
predictors for chronicity of headache in patients with episodic
migraine," Neurology 62: 788-90, 2004) is concerned with
the incidence and percentage of transition from episodic migraine to
chronic migraine. What are the findings here?
We followed 532 patients with episodic migraine for one year. 14% of the
sample developed chronic headache, defined as more than 15 days per month.
Medication overuse coexists in the majority of patients with chronic
headache and improves after withdrawal from the overused headache
medication. This suggests a causal relationship between the medication
overuse and chronicity of headache.
Our study was in line with these findings showing that patients who
overused their headache medication had a high risk of developing chronicity
of headache. One-third of patients, however, developed chronic headache
without medication overuse, suggesting that medication overuse is an
important but not the only factor determining chronicity of headache.
Finally I'd like to ask you to comment on #8 (Diener HC,
et al., "Efficacy, tolerability and safety of oral eletriptan
and ergotamine plus caffeine [Cafergot®] in the acute treatment of
migraine: A multicentre, randomised, double-blind, placebo-controlled
comparison," Eur. Neurol. 47: 99-107, 2002), which
examines the comparative efficacy and safety of intravenous aspirin in
the acute treatment of migraine.
This is another of our papers examining what works and what does not work
in the treatment of migraine. Here we looked at intravenous treatments,
which have to be used in cases where oral treatment in the emergency room
is ineffective because of vomiting or diarrhea. We conducted the study in
17 centers in Germany with a sample of 275 patients who had suffered acute
In summary, we found that subcutaneous sumatriptan and intravenous lysine
acetylsalicylate are effective treatments for patients suffering from
migraine attacks. Sumatriptan is more effective, but resulted in more
Prof. Dr. H. C. Diener M.D., Ph.D.
Department of Neurology
University of Duisburg-Essen
Professor Hans-Christoph Diener's most-cited
paper with 265 cites to date:
Albers GW, et al., “Stroke prevention with
the oral direct thrombin inhibitor ximelagatran compared
with warfarin in patients with non-valvular atrial
fibrillation (SPORTIF III) randomised controlled
trial,” Lancet 362(9397): 1691-8, 22
November 2003. Source:
Essential Science Indicators from