Learn all about headache over the centuries

In the twelfth century, Abbess Hildegarde of Bingen described her visions, later attributed to her migraine aura, in terms that are both mystical and apocalyptic: ‘I saw a great star, most splendid and beautiful, and with it an exceeding multitude of falling sparks with which the star followed southward … and suddenly they were all annihilated, being turned into black coals … and cast into the abyss so that I could see them no more’.

In 1683 Thomas Willis brilliantly described a woman with severe, periodic, migrainous headache preceded by a prodrome and associated with vomiting: ‘… beautiful and young woman, imbued with a slender habit of body, and an hot blood, was wont to be afflicted with frequent and wandering fits of headache … On the day before the coming of the spontaneous fit of this disease, growing very hungry in the evening, she eat a most plentiful supper, with an hungry, I may say a greedy appetite; presaging by this sign, that the pain of the head would most certainly follow the next morning; and the event never failed this augury … she was troubled also with vomiting’.

Migraine was distinguished from common headache by Tissot in 1783, who ascribed it to a supraorbital neuralgia ‘… provoked by reflexes from the stomach, gallbladder or uterus’. Over the next century, uBois Reymond, Mollendorf and, later, Eulenburg proposed different vascular theories for migraine. In the late eighteenth century, Erasmus Darwin , grandfather of Charles Darwin, suggested treating headache by centrifugation. He believed headaches were caused by vasodilation, and suggested placing the patient in a centrifuge to force the blood from the head to the feet. Fothergill in 1778 introduced the term ‘fortification spectra’ to describe the typical visual aura or disturbance of migraine.

Fothergill used the term ‘fortification’ because the visual aura resembled a fortified town surrounded with bastions. In 1873, Liveing  wrote the first monograph on migraine, entitled On Megrim, Sickheadache, and Some Allied Disorders: A Contribution to the Pathology of Nerve-storms, and originated the neural theory of migraine. He ascribed the problem to ‘… disturbances of the autonomic nervous system’, which he called ‘nerve storms’. William Gowers, in 1888, published an influential neurology textbook, A Manual of Disease of the Nervous System. Gowers emphasized the importance of a healthy lifestyle and advocated using a solution of nitroglycerin (1% in alcohol), combined with other agents, to treat headaches. The remedy later became known as the ‘Gowers mixture’. Gowers was also famous for recommending Indian hemp (marijuana) for headache relief.

Lewis Carroll described migrainous phenomena in Alice in Wonderland and Through the Looking Glass, depicting instances of central scotoma, tunnel vision, phonophobia, vertigo, distortions in body image, dementia and visual hallucinations. Greek and Roman ancient writings include references to ‘blighted grains’ and ‘blackened bread’, and to the use of concoctions of powdered barley flower to hasten childbirth. During the Middle Ages, written accounts of ergot poisoning first appeared. Epidemics were described in which the characteristic symptom was gangrene of the feet, legs, hands and arms, often associated with burning sensations in the extremities. The disease was known as ‘Ignis Sacer’ or ‘Holy Fire’ and, later, as ‘St. Anthony’s Fire’, in honor of the saint at whose shrine relief was obtained.

This relief probably resulted from the use of a diet free of contaminated grain during the pilgrimage to the shrine. The term ‘ergot’ is derived from the French word ‘argot’ meaning ‘rooster’s spur’. It describes the small, banana-shaped sclerotium of the fungus. Louis René Tulasne of Paris in 1853 established that ergot was not a hypertrophied rye seed, but a fungus having three stages in one life cycle, and he named it Claviceps purpurea . Once infected by the fungus, the rye seed was transformed into a spur-shaped mass of fungal pseudotissue, purple-brown in colour: the resting stage of the fungus, known as the ‘sclerotium’ (derived from the Greek ‘skleros’ meaning ‘hard’).

In 1831, Heinrich Wiggers , a pharmacist of Göttingen, Germany tested ergot extracts in animals. Among his models was the ‘rooster comb test’: a rooster, when fed ergotin, became ataxic and nauseous, acquired a blanched comb and suffered from severe convulsions, dying days later. The ‘rooster comb test’ continued to be used into the following century by investigators studying the physiologic properties of ergot11. Later Woakes, in 1868, reported the use of ergot of rye in the treatment of neuralgia. The earliest reports in the medical literature on the use of ergot in the treatment of migraine were those of Eulenberg in Germany in 1883, Thomson in the United States in 1894 and Campbell in England in 1894. Stevens’ Modern Materia Medica mentioned the use of ergot for the treatment of migraine in 1907.

The first pure ergot alkaloid, ergotamine, was isolated by Stoll in 1918 and used primarily in obstetrics and gynecology until 1925, when Rothlin successfully treated a case of severe and intractable migraine with a subcutaneous injection of ergotamine tartrate. This indication was pursued vigorously by various researchers over the following decades and was reinforced by the belief in a vascular origin of migraine and the concept that ergotamine tartrate acted as a vasoconstrictor. In 1938, John Graham and Harold Wolff14 demonstrated that ergotamine worked by constricting blood vessels and used this as proof of the vascular theory of migraine .

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