Terminology Use of the Ad Hoc Committee classification continued in the early part of this decade but proved unsatisfactory for a number of reasons. The frequently used terms “tension” or “muscle contraction” headache, for example, implied etiologies that seemed increasingly dubious. The trials necessary to test potential treatments for various headache disorders likewise exposed the weaknesses of a classification system that, according to the epidemiologist Waters, was based on “just descriptions rather than explicit definitions.”
In 1988, Cephalalgia published the first version of the International Classification of Headache Disorders (ICHD), entitled “Classification and Diagnostic Criteria for Headache Disorders, Cranial Neuralgias and Facial Pain.” Work had begun on the document 3 years before. According to the Preface, the project had involved 12 subcommittees, several public meetings, and a large amount of volunteer labor by committee members. In the Introduction, the authors wrote that “The primary use is for research, but over the course of years it will probably influence the way we diagnose patients in our daily work.” They pre-emptively warned readers, “please do not be overwhelmed” and offered the reassuring comment that the classification was “not supposed to be learned by heart.” Noting the many difficulties in classifying a group of disorders whose pathophysiology varied and that were poorly understood, the authors of this new Classification pointed out that “it has not been possible to classify patients, only to classify headaches.” Established terms such as “common” and “classic” migraine proved stubbornly durable, but gradually gave way to the more modern and descriptive terminology of “migraine without aura” and “migraine with aura.”
Pathophysiology In the early 1980s, Jes Olesen published his observations that in migraine attacks triggered by carotid angiography, reductions in cerebral blood flow demonstrated by xenon blood flow techniques were not sufficient to cause ischemia. An especially important finding was that blood flow changes did not respect large arterial territories but instead spread slowly at a rate consistent with that observed for the cortical phenomenon then known as “spreading depression of Leao.” Milner had earlier proposed this as the explanation for migraine aura, but it was not until work by Lauritzen during the 1980s that strong evidence for the link emerged.
Work by Michael Moskowitz showed plasma extravasation from cerebral vessels with stimulation of the trigeminal nerve in animals, and ideas about the underlying explanation for migraine expanded, with frequent reference to migraine as a trigeminovascular, rather than a simple vascular, disorder. A number of headache drugs were shown to block plasma protein extravasation and ideas about such sterile inflammation as a cause of pain developed.
Less evidence-based explanations were also advanced to explain various clinical phenomena. The author of a Headache article on “Opioids, Pregnancy and the Disappearance of Headache” reported “Women that have gone through this experience agree that it is one of the happiest periods in their lives . . .” He suggested that this “so-called ‘state of bliss’ ” and the disappearance of headache might be due to placental opioid-like substances such as endorphins.
Some diagnostic entities appeared in the literature that have since disappeared. A study of “Salt-induced migraine” reported in Headache remains interesting because it demonstrates an early use of placebo in a headache study. Gelatin or sodium chloride capsules were given to 25 migraine sufferers and 24 nonmigraineurs. In total, 14/15 migraineurs who got salt developed headache compared with 1/10 who received gelatin capsules. In contrast, 3/24 controls given salt and 0/24 given gelatin got a headache the next day.
Treatment In the United States, nonspecific medications were in common use for acute treatment of headache disorders. Many contained barbiturates. Perusal of Headache issues through the decade reveals numerous advertisements for barbiturate-containing drugs including Phrenelin, Empirin with codeine, and Fiorinal. Ergots were also used, and an advertisement for the branded ergotamine product Wigraine admonished readers that it should be “taken at the first symptom . . . to halt throbbing head pain before it takes hold” . . . “disintegrates 7-70 times faster than other migraine preparations” due to “a patented microgranulation process” that “bursts” the tablet apart . . .” To doctors who have lived through the recent onslaught of pharmaceutical advertisements for more modern headache treatments, these claims will sound familiar although the drugs touted have changed. In 1984, an event occurred that was destined to have far-reaching consequences for headache and headache sufferers in the next decade. Scientists at Glaxo synthesized GR 43175, a 1B/1D serotonin agonist later named sumatriptan.
The 1980s saw the serendipitious discovery by Karl Ekbom that lithium was effective in preventing cluster headache, and indomethacin was increasingly used for the newly recognized indomethacin-responsive headache syndromes. Lee Kudrow, a cluster headache sufferer himself, popularized the use of oxygen to abort cluster headache attacks. Much fundamental research on biofeedback also occurred during this decade. Headache published a description of a 5-day training program for patients run by the famed Menninger clinic in Kansas, and studies by Roy Mathew and others were published, including cerebrovascular researchers Fumihiko Sakai and John Stirling Meyer, evaluating cerebral blood flow changes with biofeedback.
Calcium antagonists and valproate were tested and entered clinical practice in the 1980s.
Dr. Ninan Mathew recounts the events leading to Food and Drug Administration (FDA) approval of valproate for migraine prophylaxis:
The interest in valproate developed both in Europe and in the U.S. more or less simultaneously around 1987-1988. There were many reasons for it. One, of course, was the fact that there were some data supporting the idea that there is cortical hyperexcitability in migraine. I had edited a Neurologic Clinics in 1990 in which Michael Welch wrote a chapter detailing the evidence in favor of cortical hyperexcitability in migraine. So, that concept was going on in 1987, 1988 and 1989, which led to the trial of valproate initially. Apart from the cortical hyperexcitability theory, one of the other key observations was that valproate, a GABA mimetic agent, acts on GABA receptors in the dorsal raphe nuclei resulting in decreased firing rate of serotonergic cells. This basic observation by Nishikawa, published in Pain Research in 1985, was the other major supporting observation which led to the use of valproate. Along with me, Neil Raskin also started using valproate in patients from 1988. The first paper on valproate (an open-labeled study) was published by Sorensen in Acta Neurologica Scandinavia in 1988. In 1991, I published an open-labeled trial of valproate in persistent chronic daily headache. (Headache 1991;31:71-74)
Abbott Pharmaceuticals, which owned valproate, was not interested to pursue the development of valproate as a prophylactic agent in migraine. It was mainly due to my constant pressure on them which led them to agree to a double-blind placebo controlled multicenter study of valproate in prophylactic treatment. The studies were positive and the first pivotal paper was published in Archives of Neurology in 1995 (Mathew, et al). In addition to our paper, there were confirming reports from Denmark (Jensen, et al) and also from Kuritzky and later, from Klapper. The positive studies led to approval of valproate. The use of valproate in migraine was not because of its comorbidity with epilepsy.
Societies, journals, and clinics In 1980, AASH had 450 members and held its annual meeting June 20-22 in San Francisco. By the close of the decade, AASH membership cost $100 annually and the journal was published 10 times a year. Readers were urged to subscribe to Headache, “now in its 29th year” at a cost of $55.00 if they did not wish to join and get the journal as a membership benefit.
The January 1980 issue of Headache opened with instructions for authors: “An original typescript and two high quality copies of all manuscripts . . . typed double-spaced on 22 × 28 cm (8½ × 11 inch), heavy-duty white bond paper . . .” Prospective authors were to send the result “. . . by first-class mail to the Editor,” who was then Donald Dalessio. His editorial board included James Couch, James Dexter, John Edmeads, C. Miller Fisher, John Graham, Lee Kudrow, Ninan Mathew, Jon Stirling Meyer, Neil Raskin, Joseph Sargent, Federico Sicuteri, and Dewey Ziegler.
The first issue of Headache published in the 1980s included a transcript of “Headache Rounds” held at the Graham Headache Center in Boston. The cases of 2 patients with headache were presented; they were being seen in weekly psychotherapy and the treatment discussion centered on psychological issues. Other articles in this issue reviewed matters of patient compliance, psychogenic headache, and a study which found that headache questionnaires were reliable, but not as valid as daily recordings of headache.
The last Headache issue of the decade was published in 1989. It contained 8 research articles, and the familiar Midrin advertisement –“interrupts migraine headache at the first sign”– was firmly established on the back cover. (A Midrin advertisement graced the back cover of the journal for over 2 decades: it debuted in the January 1981 issue of the journal, supplanting an advertisement for Esgic. The last back cover Midrin advertisement would not appear until the July/August 2001 issue, after which the back cover began to feature triptan advertisements.) Advertising copy within the journal during the 1980s touted Inderal LA –“the one to start with to prevent common migraine”– and Advil, along with Nimotop and Phrenelin.
In 1989, the editor of Headache was John Edmeads, with an editorial board consisting of Frank Andrasik, James Couch, Don Dalessio, James Dexter, Seymour Diamond, C. Miller Fisher, Lee Kudrow, Ninan Mathew, John S. Meyer, Neil Raskin, Joseph Sargent, and Seymour Solomon. The front cover design of the journal did not change during this decade.
In 1980, the International Headache Society was formed. It published the first issue of its journal, Cephalalgia, in 1981.
The bottom line The publication of the ICHD was arguably the most important event of the 1980s. Its far-reaching consequences for headache research and practice became apparent during the following decade, and it continues to wield enormous influence on thought and practice in the headache field. Another event in this decade, however, competed with ICHD as a contender for milestone status, at least as measured by the events of the next decade. This was the synthesis of sumatriptan, which along with its successor drugs dominated the attention of headache practitioners and patients in the 1990s.