Headache – What We Knew and What Is New: From a Physician Who Is Also a Patient
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.325381
Source of Support: None, Conflict of Interest: None
The Editor of Neurology India, Prof. P. Sarat Chandra, and the Editor of its supplement on Headache and Related Disorders, Prof. Debashish Choudhary, deserve our congratulations for bringing out this volume on a familiar disease disorder yet so little understood. They have managed to get a galaxy of distinguished authors from different parts of the world to update us on the diverse clinical syndromes of headaches and allied disorders, their diagnostic criteria, recent advances of their pathophysiology, and current therapeutic approaches.
I, for one, have suffered migraine headaches all my life and have also treated a large number of patients suffering from these disorders. I have served on the Editorial Board of Cephalgia at its inception. Now, having leisure time at my disposal, I have not surprisingly got curious to learn about recent advances since I lost touch with the subject after giving up my professional life three decades ago. I eagerly searched for answers that had bothered me whenever I had suffered from a migraine attack.
First, a few words about my migraine. This began at a very young age, but I was not formally diagnosed till late in life as I did not seek any medical help. Now, I understand that I suffered from common episodic migraines without aura often associated with promontory symptoms. It could occur on either side, manifested with pulsating temporal artery. Surprisingly, I had not taken any analgesics until it was forced on me by a neurosurgical colleague in Oslo, who also suffered from it. I could not believe that a simple “Saridon” (an over-the-counter common medication consisting of paracetamol, propyphenazone, and caffeine) could provide prompt relief if taken early in the course of the pain. It was then that I read more about these disorders and learned a lot from my personal experience. Over the years, I was always intrigued by several questions and searched for the answers in this supplement. However, I must confess (for the sake of co-sufferers) that notwithstanding fairly frequent attacks, I have lived a reasonably active life both socially and professionally. I also found this to be true for most people suffering from migraines and episodic attacks without aura.
Given the luxury of a lot of free time, I indulged in a personal “exploration” of what residual knowledge I had on the subject, and what new I learned, and whether I could find answers to my long-standing questions in this regard. Before I indulge in sharing these thoughts with you, let me reiterate that most articles in the supplement provided thorough, detailed, and up-to-date information on the subject – a veritable source of new knowledge. I may add that prompted by what I read in the supplement, and I searched for more information on some of these advances in recent publications.
I am humbled to learn how little I knew about migraine leave aside from the other allied disorders included in the supplement. In brief, I knew something about episodic migraine and its clinical manifestations. Also, its earlier recognized pathophysiology as a cerebrovascular disorder affecting the extracranial vessels primarily on one side of the head, especially in the temporal region. I was aware of it being of a changing concept as a neurovascular pathology originating from the neuronal activity in the brainstem and hypothalamus, later spreading to some parts of the cerebral cortex. In 1987, Raskin et al. pointed out that headaches may arise from focal perturbation of the brain. Lot was recent work using advanced investigations such as electroencephalogram (EEG), functional magnetic resonance imaging (fMRI), and positron emission tomography (PET) scan studies that elaborated the neural involvement in the different stages of migraine. I was not familiar with these advances, mainly reported after the 1990s, the year of my superannuation.
Let me quote the source of these since I have now learned a few.
Weiller et al., in 1995, claimed their study of PET scans showing brainstem involvement in the pathophysiology of migraine. They also reported increased neuronal activity in the cerebral hemisphere in the cingulate, auditory, and visual cortex. Angelin et al., in 2004, using EEG studies, reported increased alpha-band synchronization in patients with migraine, while healthy subjects showed a decrease. I would like to quote the following studies of relevance. These include Cao et al. (2002) with MRI studies, Afridi et al. (2005) and Denuelle et al. (2007) using PET scan, Chong et al. (2016) using MRI resting-state functional connectivity data, Karsan and Goadsby (2020) in a mini-review of imaging the premonitoring phase of migraine. All these have pointed out the predominant role of brainstem activation in the pathophysiology of migraine onset and continuation. The ipsilateral dorsolateral pontine nucleus was the most common region affected in these studies. A systemic review of the pathophysiology of migraine had been provided by Goadsby et al. (2017). The most detailed analysis on the subject was carried out by Schulte et al. (2020), who recorded the migraine brain network continuous resting-state fMRI over 30 days. He concluded, “The unique data suggests that certain connectivity changes in dopaminergic centers between the dorsal pons and hypothalamus are important in migraine attack generation and sustainment. Cao et al. (2002) had claimed to be the first one to demonstrate activation of the hypothalamus in addition to the brainstem. They also found activation of the red nucleus and substantia nigra. Naegel and Obermann reporting in Neurology India Supplement 2021, summarized the subject's current status based on PET and fMRI in various types of headaches, including migraine, and concluded, “It remains undisputed that the hypothalamus and the brainstem are key structures as the pathophysiology of these disorders.”
My comment: Notwithstanding the accumulation of a large amount of neuroimaging data as also a certain degree of consensus about the brain region(s) involved in the initiation and maintenance of a migraine attack, there is no explanation about the cause of initiation of neural activity, its involvement of a specific region, its limitation to one side, or its production of vasodilation and pain. The new observations have added new knowledge, but its clinical significance and its subsequent use elude us so far.
In addition to the “common garden” variety of migraine (episodic without aura), we also had sound clinical knowledge about the one with aura, its relatively higher risk to life due to associated cerebral vascular pathology. While treatment of the acute episodes was well-known, drugs for prevention and permanent cure were not. Sumatriptan had already been introduced, but most clinicians, including us, were reluctant to use it owing to its toxic effects. Notwithstanding some ongoing trials of new drugs for prophylaxis and cure, there are still none available for routine clinical use either for prevention or treatment of acute attack.
While our neurology colleagues might have been aware of the entity of chronic migraine, at least most neurosurgeons, including myself, were not. First, let me point out that the International Headache Society included this entity in the third edition of the Classification of Headache Disorders (2018) even though several papers were already published in the 2000s. At this time, it was pointed out that “a greater understanding of the pathophysiology of migraine during the last decade has led to the development of the first targeted treatment for chronic migraine” (Gribbin et al. ).
Similarly, I presume that very few clinicians were aware of the entity “Medication Overuse Headache” around the 1980s. Although first described by Horton and Peters in 1963, it was included in the first edition of International Classification of Headache (ICH) in 1988 as Drug-Induced Headache and later changed to Medicine Overuse Headache only in 2004, the second edition of the ICH.
The clinical entities of Cluster Headache, Tension Headache, Occipital Neuralgia, and Trigeminal neuralgia were well-established very early in our career. However, at least I have learned only after going through the supplement, conditions such as paroxysmal hemicrania (PH), hemicrania continua, trigeminal autonomic cephalalgia, SUNCT (syndrome of short-lasting, unilateral neuralgiform headache with conjunctival injection and tearing), and SUNA (short-lasting unilateral neuralgiform headache with autonomic symptoms). Interestingly, based on only a few clinical studies, Sjaastad from Norway described these syndromes in 1978. These entities were accepted in the second edition of the ICH and are probably well-known to neurologists today. However, it may still be unknown to most neurosurgeons.
Sjaastad et al. were also the first to report PH in 1976. This was also accepted as a diagnostic entity in the second edition of the ICH in 2004, by which time others also reported such patients. fMRI studies placed PH in the group of trigeminal autonomous cephalalgias along with hemicrania continua, SUNCT, and SUNA.
The Neurology India Supplement 2021 described all these conditions in detail. These include their clinical, PET, fMRI, and EEG characteristics and current therapy. However, after going through all these and some more reviews and case reports, I still have several unanswered questions on migraine headaches. I dare to mention these below, hoping some author or any reader could enlighten me on these.
Finally, let me conclude with some lessons learned from the latest information on headaches and allied disorders that have more general applications.
Observant clinicians, like my old friend Sjaastad from Norway, in 1974, first described PH based on only a few cases. This was later accepted as a diagnostic entity by the second edition of the ICH in 2004. He also identified the entity of SUNCT in 1978 based on only a few cases. The ICH second edition later acknowledged this as a distinct entity. Similarly, Horton and Peters first described a few instances of “medicine overuse headache” in 1963. This was later included in the first edition of the ICH in 1988. These conditions were based purely on clinical observations and even today are diagnosed based on clinical criteria.
It is evident from the above that astute clinical observation by a scientifically oriented clinician can identify new disease disorders without any sophisticated tools. This is important to realize in the present-day medical practice. The patients are often sent for laboratory investigation without carefully listening to their symptoms or details of the illness. No doubt, detailed laboratory investigations are necessary to explore disease biology to search for therapeutic targets.