Migraine, Human Genetics and a Passion for Science.

This note reflects on my collaborations with Nick Martin and the GenEpi group over the past 20 years. Over the past two decades, our work together has focused on gene mapping and understanding the genetic architecture of a wide range of traits with particular foci on migraine and common baldness. Our migraine research has included latent class and twin analyses cumulating in genome-wide association analyses which had identified 44 (34 new) risk variants for migraine. Leveraging these results through polygenic risk score analyses identified subgroups of patients likely to respond to triptans (an acute migraine drug), providing the first step toward precision medicine in migraine [Kogelman et al. (2019) Neurology Genetics, 5, e364].

Surgical Treatment of Migraine Headache: Back to the Future.

Understanding the history and evolution of ideas is key to developing an understanding of complex phenomena and is the foundation for surgical innovation. This historical review on migraine surgery takes us back to the beginnings of interventional management for migraine centuries ago, and reflects on present practices to highlight how far we have come. From Al-Zahrawi and Ambroise Paré to Bahman Guyuron, two common themes of the past and present have emerged in the treatment of migraine headache. Extracranial treatment of both nerves and vessels is being performed and analyzed, with no consensus among current practitioners as to which structure is involved. Knowledge of past theories and new insights will help guide our efforts in the future. One thing is clear: Where we are going, there are no roads. At least not yet.

The Migraine Postdrome.

PURPOSE OF REVIEW: The migraine postdrome is the least studied and least understood phase of migraine. This article covers the salient features of the migraine postdrome and provides insight into the history, clinical symptoms, and future implications of this phase of migraine. RECENT FINDINGS: Prospective electronic diary studies have shown that patients are left disabled with various nonheadache symptoms in the migraine postdrome, and 81% of patients report at least one nonheadache symptom in the postdrome. Hence, it is important to understand this phase better and ensure that more effective treatments become available in the future to lessen the morbidity associated with this phase. Functional imaging shows widespread reduction in brain-blood flow in the postdrome, which explains the multitudes of symptoms experienced by patients. SUMMARY: The disability related to migraine is not exclusive to the headache phase but extends into the postdrome phase and is associated with several nonheadache symptoms that prolong the symptoms experienced by patients with migraine. Further research into the postdrome is crucial to improve our overall understanding of migraine mechanisms. This knowledge may also help to treat the concurrent nonheadache symptoms better in the future. Novel neuroimaging techniques provide a valuable noninvasive tool to push the frontiers in the understanding of migraine pathophysiology. These methods may help shed further light onto the possible links between key brain structures and networks that could be implicated in the pathophysiology of the various migraine phases.

Some Notes on Papyrus Ebers, Ancient Egyptian Treatments of Migraine, and a Crocodile on the Patient's Head.

Modern literature about the history of migraine treatments often starts with an ancient Egyptian remedy said to be from Papyrus Ebers that involves crocodiles that should be wrapped around the head. A fresh look on this treatment shows the need for revision on many points, including the source of the remedy, its content and meaning, and further implications for the history of Papyrus Ebers.

Descriptions of vestibular migraine and Menière's disease in Greek and Chinese antiquity.

Background Vestibular migraine and Menière's disease are two types of episodic vertigo syndromes that were already observed in Greek and Chinese antiquity. Descriptions first appeared in the work of the classical Greek physician Aretaeus of Cappadocia, who lived in the 2nd century AD, and in Huangdi Neijing, a seminal medical source in the Chinese Medical Classics, written between the 2nd century BC and the 2nd century AD. Aim The aim of this paper is to search in Aretaeus' book De causis et signis acutorum et chronicorum morborum and in Huangdi Neijing for descriptions of vertigo co-occurring with headache or ear symptoms that resemble current classifications of vestibular migraine or Menière's disease. Results Aretaeus describes a syndrome combining headache, vertigo, visual disturbance, oculomotor phenomena, and nausea that resembles the symptoms of vestibular migraine. In the Chinese book Huangdi Neijing the Yellow Thearch mentions the co-occurrence of episodic dizziness and a ringing noise of the ears that recalls an attack of Menière's disease. Conclusions The descriptions of these two conditions in Greek and Chinese antiquity are similar to the vertigo syndromes currently classified as vestibular migraine and Menière's disease. In clinical practice it may be difficult to clearly differentiate between them, and they may also co-occur.

A Historical Recount: Discovering Menière's Disease and Its Association With Migraine Headaches.

OBJECTIVES: In evaluating the historical context of the first description of Menière's disease, its association with migraine headaches is compelling. We have outlined the events and observations of Prosper Menière, which led him to establish a link between migraine headaches and his eponymous disease. STUDY DESIGN: Prosper Menière's original French writings were translated by our group and used to recount his observations and thoughts. Miles Atkinson's English translations were used as a reference. Additional otological texts of the era were also reviewed as it relates to Menière's disease. METHODS: Prosper Menière wrote a series of four articles 1 year before his death. In one of these articles, he makes references to migraine headaches on several occasions. These original writings were analyzed, and the physical findings he described were interpreted based on their relation to migraine headaches. RESULTS: The passages in his published articles provide historical insight into Menière's observations. His writings describe in detail symptoms of migraine headaches uniquely evident in his patient population. Through his observations, he recognized that in addition to exhibiting symptoms of tinnitus, hearing loss and vertigo his patients also suffered from migraine headaches. CONCLUSIONS: Although his colleagues discounted Menière's theory concerning migraine headaches, he continued to make deductive inferences and publish his findings, leading to the association of migraine headaches and Menière's disease. Today, this association continues to be debated, adding to Prosper Menière's legacy.

A review on the management of migraine in the Avicenna's Canon of Medicine.

Migraine is a common type of headache which has a deep history dating back thousands of years. Avicenna (980-1032), a Persian scholar, made a great contribution to neurology including headache and migraine. The aim of this study is to consider Avicenna's description about migraine (Shaghighe in Persian language) including definition, etiology and intervention. Also, his definition and treatment approaches were considered based on current concepts and findings. Although Avicenna believed in humoral theory and divided migraine into two categories, hot and cold, and suggested special treatments for them as well as general considerations, most of his definitions and explained pathologies are supported by current concepts of medicine. He believed that the migraine can result from bone of skull and also intra-parenchymal; or from skull underneath membrane (dura-mater); or reaching substances from the painful side or from outer vein and arteries (extra cranial); or from brain and meninges (pia-mater). Furthermore, current findings show most medicinal plants mentioned by Avicenna for the treatment of migraine can have potentially significant effects such as remedies which stop central and peripheral sensitization [anti-neuroinflammatory agents, decreasing nitric oxide level, cyclooxygenase (COX)-2 inhibitors], as well as serotonergics, neuroprotective agents and analgesics.

The Journey to Establish CGRP as a Migraine Target: A Retrospective View.

In this retrospective, Dr. Lars Edvinsson recounts early steps and milestones in our understanding of the neuropeptide calcitonin gene-related peptide (CGRP) in the trigeminovascular system and its role in migraine. The discovery of the presence and function of CGRP and other neuropeptides in the cerebral vasculature and its sensory innervation is described. He relates the seminal finding that CGRP is uniquely released during migraine and the journey to develop blockers of CGRP effects. Now, over 30 years since its discovery, CGRP has become the target for a number of promising novel treatments for migraine patients.

Osler on migraine.

William Osler's 1892 textbook The Principles and Practice of Medicine became the dominant medical text in the English-speaking world. Osler was labeled a therapeutic nihilist by some. The topic of migraine, including treatment, was succinctly covered in his text. The objectives of this study were to review Osler's thoughts on migraine, and outline his therapeutic recommendations. Preventively Osler mentioned bromides, iron, arsenic, nitroglycerin, and cannabis. Acutely he recommended coffee, chloroform, cannabis, antipyrin, antifebrin, phenacetin, caffeine citrate, nux vomica, or ergot. He thought cannabis was the most satisfactory remedy. Osler was not a therapeutic nihilist when it came to migraine, and his treatment recommendations were similar to other writers of his time. Osler did not draw upon his personal experience to contribute new knowledge about migraine. Regardless, given the popularity and clarity of his text, Osler's well-summarized migraine chapter had a great influence on practicing physicians.

Huygens' headache.

BACKGROUND: Christiaan Huygens (1629-1695) was a Dutch mathematician, physicist, and astronomer. He became well-known as inventor of the pendulum clock and described light as a wave phenomenon. He became Fellow of the Royal Society (London) and member of the Académie des Sciences (Paris). From the correspondence with family members and famous scientists, we learn that he suffered from frequent headaches. AIM: To study Huygens' 22-volume Oeuvres Complètes (1888-1950) to find letters in which his headaches are mentioned and translate pertinent sections into English. CONCLUSIONS: Although a posthumous diagnosis of Huygens' headaches is somewhat hazardous, the recurrent episodes with incapacitating headache and family history over two generations are suggestive for migraine. It becomes clear that it impeded his writing, reading, and research. From the letters we get an impression of the impact of the headache upon his life and the treatments that were applied in the 17th century.