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Edward Henry Sieveking (1816-1904) was a professionally successful and well respected nineteenth-century London physician who, over the span of some half a century, continuously held appointment to British royalty, including Queen Victoria and King Edward VII. In 1858, he published a monograph On Epilepsy and Epileptiform Seizures , with a second edition in 1861. In both editions, he described an entity cephalalgia e pileptica that comprised the occurrence of headache in association with phenomena that resembled the premonitory symptom of some epileptic seizures. However, the sufferers did not have epilepsy, in that they did not experience generalized convulsions. Sieveking, like most of his British contemporaries, had little awareness of the existence of the variety of migraine phenomena apart from headache itself. In retrospect, it seems likely that migraine with aura probably was the main basis of the disorder Sieveking designated, one that later may have been termed migralepsy .

Objectives: To analyze the records of the pregnancies of 2283 Australian women with epilepsy in the Australian Register of Antiepileptic Drugs in Pregnancy database to identify neurological factors relevant to the Cesarean sections carried out in these pregnancies., Results: The Cesarean section rate in Australian women overall increased by an average of 0.59% annually over 20 years, from 26.0% to its calculated 2020 value of 37.3%. For the operations in women with epilepsy, the corresponding figures were 0.71% annually, and 34.4% and 48.7%. The average annual rate of increase for pre-labor operations was 0.89% to a 2020 value of 39.1%, the annual rate for operations during labor showing no statistically significant change. Multivariate regression analysis identified a number of characteristics of women with epilepsy that were statistically significantly associated with an increased likelihood of Cesarean section, but of these only seizures continuing to occur in the third trimester and having chronic illness, in particular migraine, were neurological ones. In 70 migraine-affected women, the Cesarean section rate was 51.4%, compared with 39% in the remaining pregnancies (P < 0.05)., Conclusions: Having seizures in the final trimester of pregnancy and having chronic neurological illness, especially migraine, favored Cesarean section being carried out in Australian women with epilepsy, but did not adequately account for the increasing rates of occurrence of the operation over the past 20 years., Competing Interests: Conflicts of interest F.J.E. Vajda has received research support for the Australian Pregnancy Register from the Epilepsy Society of Australia, NHMRC, RMH Neuroscience Foundation, Epilepsy Action, Sanofi-Aventis, Eisai, UCB Pharma, and Sci-Gen. T. O’Brien has received research support from the Epilepsy Society of Australia, NHMRC, RMH Neuroscience Foundation, Sanofi-Aventis, UCB Pharma, and Sci-Gen and Eisai. P. Perucca is supported by an Early Career Fellowship from the National Health and Medical Research Council (APP1163708), the Epilepsy Foundation, the Royal Australasian College of Physicians, The University of Melbourne, Monash University, the Weary Dunlop Medical Research Foundation, Brain Australia, and the Norman Beischer Medical Research Foundation. He has received speaker honoraria or consultancy fees to his institution from Chiesi, Eisai, LivaNova, Novartis, Sun Pharma, Supernus, and UCB Pharma, outside the submitted work. He is an Associate Editor for Epilepsia Open. J.E. Graham, A.A. Hitchcock, R. Kuhn, C.M. Lander, and M.J. Eadie have no relevant conflicts of interest to declare. They have not received any personal funding from outside bodies in relation to their roles in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: This study examined the use of triptan derivatives in Australia between 1997 and 2015, based on a national drug reimbursement database, and compared patterns of use with available international data., Methods: We obtained publically available data on the number of prescriptions for triptans marketed in Australia (sumatriptan, eletriptan, rizatriptan, zolmitriptan, naratriptan). Dispensed use was measured as defined daily dose (DDD per 1000 population per day) for Australia's concessional beneficiaries (low-income earners, people with disabilities, and seniors)., Results: Total triptan use increased at an average annual rate of 112% over the 18-year period. Sumatriptan was the preferred triptan throughout (average annual increase 45%). Zolmitriptan and naratriptan use peaked in 2004, then decreased. Rizatriptan and eletriptan became available in 2010. There were 3.2-fold and 5.9-fold annual increases in their use from 2011 to 2105. There was some evidence suggesting that pattern of triptan use in concessional beneficiaries probably reflected pattern of overall triptan use in Australia., Conclusions: The use of triptan derivatives in Australia per head of population for treating migraine attacks continued to increase over the 18-year period studied, with use of recently introduced derivatives more than substituting for decreased use of older triptans. This suggests that the available treatments of migraine attacks had achieved what were considered less than adequate therapeutic outcomes., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The modern understanding of the pathogenesis of migraine, based on the concept that it is a neurovascular disorder, is often thought to have emerged from the work of Harold Wolff in the period 1932-1962. However, over the preceding 300 years, from William Harvey onwards, various hypotheses of the pathogenesis of migraine had been proposed, a few bearing reasonably strong resemblances to Wolff's ideas, though based on less adequate evidence. Many of these earlier hypotheses regarded migraine either primarily as a vascular (e.g., Willis, Wepfer, Latham) or as a neural disorder (e.g., Harvey, Lieving and his 'nerve storms'). There were also variations around these two major themes and in the 19th Century a number of neurovascular type hypotheses emerged assigning a major role in migraine pathogenesis to the autonomic nervous system. In addition, during the three centuries there were a number of other hypotheses based on different postulated pathogenic mechanisms, some quite ingenious, which had relatively brief vogues. No hypothesis has yet proved capable of explaining all the features of migraine satisfactorily.

Over the past decade the various triptan derivatives have been accepted as the most effective available agents for relieving migraine attacks. Prior to that, for a period of half a century, ergotamine was the only 'specific' available for this purpose. In 1918, Stoll had isolated it from the various alkaloids present in extracts of the sclerotia of the fungus Claviceps purpurea (ergot), which grow on rye and, to a lesser extent, on other grasses. By 1925 ergotamine was beginning to be used to treat migraine attacks. However, as ergotamine was present in extracts of ergot, which had been used to treat migraine first in Italy in 1862, and then by Edward Woakes (1868) in England, and after him by Albert Eulenburg in Germany (1883), the drug had actually come into unrecognised use for the disorder more than half a century before ergotamine itself was known to exist. Unfortunately, because of ergotamine's chemical and pharmacokinetic properties, extracts of ergot of rye were incapable of producing consistent therapeutic results, so that general acceptance that the first specific substance for migraine treatment existed had to wait until pure ergotamine was available for administration.

During the period 1778-1780 the Swiss physician Samuel A A D Tissot (1728-1797) published his Traité des nerfs et de leur maladies, a work which continued to be available and widely influential until at least the middle of the following century. It contained a long chapter dealing with migraine, based on the earlier literature on the topic and on Tissot's own clinical experience. The work appeared at the beginning of the modern era of interest in migraine, and provided the first reasonably adequate and systematic account of the disorder to become widely available. Its descriptions of migraine phenomena have an enduring validity, though Tissot's ideas on the pathogenesis of the disorder, viz. that it usually arose from stomach disturbance, were not founded on satisfactory evidence and are long since superseded.

The drugs which provide specific relief from migraine attacks, the ergopeptides (ergotamine and dihydroergotamine) and the various 'triptans' (notably sumatriptan), are often prescribed for persons already taking various migraine preventative agents, and sometimes drugs for other indications. As a result, migraine-specific drugs may become involved in drug-drug interactions. The migraine-specific drugs all act as agonists at certain subclasses of serotonin (5-hydroxytryptamine; 5-HT) receptor, particularly those of the 5-HT1D subtype, and produce vasoconstriction through these receptor-mediated mechanisms. The oral bioavailabilities of these drugs, particularly those of the ergopeptides, are often incomplete, due to extensive presystemic metabolism. As a result, if migraine-specific agents are coadministered with drugs with vasoconstrictive properties, or with drugs which inhibit the metabolism of the migraine-specific agents, there is a risk of interactions occurring which produce manifestations of excessive vasoconstriction. This can also occur through pharmacodynamic mechanisms, as when ergopeptides or triptans are coadministered with methysergide or propranolol (although a pharmacokinetic element may apply in relation to the latter interaction), or if one migraine-specific agent is used shortly after another. When ergopeptide metabolism is inhibited by the presence of macrolide antibacterials, particularly troleandomycin and erythromycin, the resultant interaction can produce ergotism, sometimes leading to gangrene. Similar pharmacokinetic mechanisms, with their vasoconstrictive consequences, probably apply to combination of the ergopeptides with HIV protease inhibitors (indinavir and ritonavir), heparin, cyclosporin or tacrolimus. Inhibition of triptan metabolism by monoamine oxidase A inhibitors, e.g. moclobemide, may raise circulating triptan concentrations, although this does not yet seem to have led to reported clinical problems. Caffeine may cause increased plasma ergotamine concentrations through an as yet inadequately defined pharmacokinetic interaction. However, a direct antimigraine effect of caffeine may contribute to the claimed increased efficacy of ergotamine-caffeine combinations in relieving migraine attacks. Serotonin syndromes have been reported as probable pharmacodynamic consequences of the use of ergots or triptans in persons taking serotonin reuptake inhibitors. There have been two reports of involuntary movement disorders when sumatriptan has been used by patients already taking loxapine. Nearly all the clinically important interactions between the ergopeptide antimigraine agents and currently marketed drugs are likely to have already come to notice. In contrast, new interactions involving the triptans are likely to be recognised as additional members of this family of drugs, with their different patterns of metabolism and pharmacokinetics, are marketed.

Plasma aspirin and salicylate levels were measured at intervals over a two hour period during migraine attacks in 10 subjects given 900 mg oral aspirin alone, in 10 subjects given 900 mg oral aspirin plus 10 mg oral metoclopramide, and in 10 subjects given 900 mg oral aspirin plus an intramuscular injection of 10 mg metoclopramide. Higher peak aspirin and salicylate levels occurred in patients given aspirin with metoclopramide. Aspirin tended to appear in plasma earlier in patients given aspirin with oral metoclopramide than in patients given aspirin alone, or aspirin with intramuscular metoclopramide. Patients given aspirin with oral metoclopramide tended to obtain better early pain relief than the other two treatment groups, though by one hour from dosage use of injected metoclopramide was also associated with better pain relief.

A retrospective study of the efficacy of soluble aspirin in migraine has been carried out. Data were available for 61 patients. These patients differed in only relatively minor ways from the remainder of the population of migraine sufferers referred to a neurological consultative practice. Soluble aspirin usually or always relieved migraine attacks in 44% of these patients, and sometimes relieved the disorder in another 25%. Adverse effects mainly nausea and vomiting, were reported by 16% of patients only, and in some cases nausea and vomiting may have been due to migraine rather than to the drug. Response to aspirin was unrelated to factors such as the patient's age, sex and duration of migraine history, and to the severity of migraine or occurrence of nausea and vomiting during attacks. However, the presence of a migraine aura appeared to improve the chances of a response to aspirin. The aura may have permitted earlier recognition that migraine was present, and thus allowed earlier aspirin intake at a stage when it had a better chance of influencing migraine mechanisms.

Plasma aspirin and salicylate concentrations were followed after 600 mg of a new palatable glycinated preparation of aspirin was given to six healthy male volunteers in an attempt to investigate whether pre-gastric absorption of aspirin could occur. In each subject the drug was administered by three different routes, viz. (i) swallowed with water, (ii) dissolved sublingually and retained in the mouth, and (iii) allowed to disperse on the tongue, and then swallowed without water intake. Using the latter route of administration and the same aspirin formulation, plasma aspirin and salicylate concentrations were also followed in 10 patients during acute migraine attacks. These results were compared with those from another 10 migraineurs given 600 mg of soluble aspirin swallowed with water during attacks. Aspirin and salicylate pharmacokinetic parameters (Cmax, tmax, t1/2, Kabs and AUC) in the normal volunteers were not significantly different (p greater than 0.05) whether glycinated aspirin was swallowed with water or swallowed without water after dispersion in the mouth. However, negligible aspirin was absorbed when the glycinated preparation was retained in the mouth. In migraine patients, there was no significant difference (p greater than 0.05) between the bioavailabilities of soluble aspirin swallowed with water (AUC = 5.7 +/- 2.3 mg h/l) and glycinated aspirin swallowed without water (AUC = 4.4 +/- 1.6 mg h/l). There also was no significant difference (p greater than 0.05) when the time courses of pain relief were compared, both treatments being associated with a significant (p less than 0.01) analgesic effect. The glycinated aspirin was thus bioequivalent to swallowed aspirin but has no advantages for migraineurs over soluble aspirin if water is readily available for self-administration.