Comorbidities of Migraine
Our sincere thanks to Barb Wojtkowska and other members of the Migraine Australia Research Working Group for compiling this information.
When we speak about comorbidities and associated conditions of migraine, we are talking about 3 situations:
- When one condition makes it more likely to have another condition at the same time; e.g. migraine and depression. These are comorbid conditions.
- When one condition may be a risk factor for other conditions; e.g. migraine may be a risk for stroke.
- A condition that may contribute to the severity or frequency of migraine attacks; e.g. obesity may increase the risk of developing chronic migraine.
A good example of research into migraine and comorbid conditions was the MAST study, by Buse et al., (2020), which surveyed over 90,000 people, 15,133 who live with migraine. Not only did the study find a number of conditions associated with migraine (Fig 1.), they also found people with more headache days per month and worse pain have an increased risk for almost all conditions; most significantly, comorbid gastric ulcers/GI bleeding, diabetes, anxiety, depression, insomnia, asthma and allergies/hay fever.
Figure 1. Odds ratio for migraine vs. non-migraine for each health condition
Source: Buse et al., 2020
Adverse Childhood Experiences (ACEs) and Post-Traumatic Stress Disorder (PTSD)
ACEs, which include physical abuse, sexual abuse, emotional abuse and neglect, are among the most intense sources of stress that children and youth may suffer early in life. Such stress in childhood has life-long consequences for a person's health and well-being. It can disrupt early brain development and compromise functioning of the nervous and immune systems. ACEs can also have a negative impact on the severity and disability of migraine and chronic pain conditions. Childhood abuse can also be a risk factor for migraine chronification.
Similarly, PTSD is more common among people living with migraine than those who do not. In specialist headache clinic studies, between 22-30% of headache patients fulfilled PTSD criteria and in veteran (i.e. people who have served in the military) groups, the prevalence of PTSD was even greater (Peterlin, B. L., Nijjar, S. S., & Tietjen, G. E., 2011). The population wide prevalence of PTSD is around 5%. In the case of PTSD, commonly the trauma event(s) precedes the onset of migraine attacks, so it can be said that having PTSD may increase the risk of developing migraine attacks or having more severe migraine symptoms.
A recent twin study looking at the genes related to PTSD found some common genes between PTSD and migraine, and that those who have PTSD without migraine have different PTSD genes (Bainomugisa, C. et al 2021). Listen to our interview with Associate Professor Divya Mehta from the Centre for Genomics and Personalised Health at QUT.
It should be noted that while PTSD is a strong predictor of migraine attack onset, trauma exposure alone is not as strong an indicator. Rather, the development and severity of PTSD symptoms resulting from such traumatic or stressful exposure have a greater role in triggering migraine symptoms.
Asthma and allergies
Asthma is a chronic disease of the lungs that can present with a spectrum of severity. Often, people will have allergic rhinitis (hay fever) before developing asthma and 70% will continue to have some sort of allergy along with asthma. Asthma, hay fever, chronic bronchitis and allergy were all found to be comorbid with headache development (1.3-1.5 times as likely) as reported in the review by Mehle M. E. (2012).
Asthma is a risk for migraine and migraine is a risk for asthma – the relationship works both ways. According to a meta-analysis by Wang, L., et al (2021), migraine was associated with 54% increased prevalence and 42% greater risk of asthma, and asthma is associated with 45% increased prevalence and 47% greater risk of migraine.
These chronic conditions share inflammatory, genetic and immune dysfunction aspects; and both conditions may be triggered by diverse allergens and precipitating factors (anything from seasonal weather changes to stress) acting on various systems within the body. Although a direct relationship is difficult to establish, people living with migraine and diagnosed with asthma are more at risk of developing chronic migraine. Since worsening of one condition is likely to cause a worsening of the other, the primary aim of treatment is to prevent attacks and provide effective rescue treatment when attacks do occur.
Among allergy conditions, rhinosinusitis (an infection of the sinuses) often presents with head pain and many people believe they are suffering from “sinus headache”, whereas, between 50% and 80% are really experiencing migraine. A number of chemicals and neuropeptides are involved in both migraine and allergic rhinitis (such as histamine, substance P and calcitonin gene-related peptide (CGRP)) and they share the same nerve pathways.
While some people find that eliminating or avoiding certain foods (or chemicals in foods) and drinks reduces their migraine frequency, the most definitive way to be sure if someone has a food allergy or intolerance would be to have an allergy skin test or to go through an exclusion diet and slowly introduce potential food triggers one by one, observing the body’s reaction. The most solid evidence for food triggers and intolerance is for tyramine found in foods such as aged cheeses, cured or smoked meat, pickled food (e.g. sauerkraut), some beans, over-ripe fruit and some beers.
Cardiovascular disease and hypertension
Cardiovascular disease is an umbrella term for all diseases which affect the heart, or blood vessels in any part of the body.
A large study by Kurth et al., 2016, followed 23,000 nurses with migraine, but without cardiovascular disease at baseline, since 1989, with follow-ups every 2 years. The study found that migraine increases the risk of a range of cardiovascular diseases including stroke, myocardial infarction (heart attack) and angina. An unexpected and important result was that associations between migraine and cardiovascular disease were similar across subgroups of women: age (<50/≥50); smoking status (current/past/never); hypertension (yes/no); postmenopausal hormone therapy (current/not current); and oral contraceptive use (current/not current). This means that migraine is a greater risk factor for cardiovascular disease than all of these commonly-known risk factors.
Migraine with aura roughly doubles the risk of heart or coronary artery disease. But, results are ambiguous because of other factors such as smoking, uncontrolled blood pressure, high cholesterol, genetics, diabetes, obesity and birth control pills also increase the risk. Caution should be taken with the use of triptans, dihydroergotamine (DHE) and non-steroidal anti-inflammatory drugs (NSAIDS) because of their heart and vascular potential risks. Alternatives might include other classes of medication or non-pharmacological treatments such as nerve blocks or trigger point injections. Preventative approaches including medications and lifestyle approaches (not smoking, avoiding excess alcohol, etc.) are important for people who have cardiovascular illnesses along with migraine.
While hypertension (high blood pressure) is almost always a high risk factor for any cardiovascular disease, its relationship to migraine is inconsistent. Some studies have found that uncontrolled, long term (more than 9 years) hypertension is associated with migraine. Prudenzano et al, 2005, highlighted the fact that hypertension often occurred with other risk factors, such as increasing age, and consumption of alcohol and coffee. The fact that medications such as beta-blockers, calcium antagonists, etc., are used for migraine prevention complicates any interpretations about the relationship between the conditions.
Peripheral arterial disease (PAD), sometimes referred to as peripheral vascular disease (PVD), is mostly due to atherosclerosis (a narrowing and hardening of arteries). It mostly occurs in males over 60yo or those who have other risk factors such as smoking, diabetes mellitus, hypertension, high cholesterol, coronary artery disease and stroke. However, the MAST study found that severe headache pain intensity was associated with nearly 3 times the odds of peripheral artery disease. In fact, Kuo et al., 2020, found that the longer a person has lived with migraine, their risk of developing PAD increases; migraine may even be an early predictor for the development of PAD.
Chronic Fatigue Syndrome (CFS) or myalgic encephalomyelitis (ME)
Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) - commonly shortened to ME/CFS, affects many body systems and presents with: extreme fatigue (lasting more than 6 months) worsening with activity; difficulty with memory and concentration (brain fog); sleep disturbances; and dizziness worsening on standing. Headache, most often fulfilling migraine criteria, is also often reported by people with CFS.
Since most of these symptoms can frequently occur with migraine, particularly chronic migraine, it can be difficult to separate the two. On the whole, a diagnosis of chronic fatigue syndrome is given if there is no underlying medical condition, although it is important to note that the cause of CFS is largely unknown. When a person has a diagnosis of migraine, there is an existing medical condition. To complicate matters, both migraine and CFS often occur alongside other conditions such as irritable bowel syndrome, fibromyalgia, and temporomandibular (jaw) joint disorder.
Having said that, Lau, C. I., et al., 2015, conducted a large study which found that the risk of CFS was 1.5 times higher in people who had migraine and that the risk of ME/CFS increased with age (>65). They suggested that there may be shared underlying mechanisms, such as central sensitisation or mitochondrial dysfunction (where the cells that produce energy don’t work as they should). Genetic and environmental factors may also have a role, although it is important to note that the cause of ME/CFS
Depression and / or anxiety
Depression is one of the most common comorbidities of migraine, occurring up to 2.5 times more than in the general population. It occurs more frequently among those with chronic migraine and migraine with aura. In extreme cases, depression along with migraine may lead to suicide ideation. In more moderate cases, the combination can be extremely disabling.
The relationship between depression and migraine is bidirectional (operates both ways). It has been suggested there are similar underlying pathophysiologic and genetic mechanisms. Treating depression with tricyclic antidepressants and psychological approaches (such as cognitive behaviour therapy, mindfulness, etc.) can also have a beneficial effect on migraine, which is indicative that both conditions share some common causative mechanisms.
Anxiety can occur along with both depression and migraine. Anxiety disorders (especially generalised anxiety disorder (GAD), obsessive compulsive disorder (OCD) and panic disorder (PD)), are 2-5 times more common in people with migraine than in the general population. The rate increases for chronic migraine.
People with anxiety disorders (especially panic attacks) and migraine tend to have increased migraine frequency, increased disability, higher risk of chronification and higher risk of medication overuse. The two conditions can have similar manifestations such as functional impairment, gastrointestinal (nausea), autonomic (dizziness), affective (fear) symptoms during attacks, plus the worry about further attacks. As with the comorbidity of depression, those with anxiety have a severely reduced quality of life. And similarly to depression, there is a bi-directional relationship between anxiety and migraine. There also appear to be common genetic and biological mechanisms at play.
Concussion, sometimes called mild traumatic brain injury (TBI), occurs after an injury to the head. Often this is a result of a sports head injury, a fall, or whiplash; as can happen in car accidents when the neck moves rapidly and forcefully backwards and forwards.
A person with concussion may experience a range of symptoms including: headache; nausea or vomiting; dizziness; confusion; sensitivity to noise and light; drowsiness; and altered mental state that may include unconsciousness. All of which are difficult to distinguish from migraine. Seifert T. (2018) noted that posttraumatic headache (PTH) and migraine both involve inflammatory processes in parts of the brain and changes to neurochemical systems which are behind some of the symptoms common to both conditions. He further observed that when migraine is misdiagnosed as concussion, effective treatment is delayed; while if concussion is misdiagnosed as migraine, the person is exposed to potential further sports injury risks.
Migraine is a primary headache disorder, which means it has no other cause. Posttraumatic headache, mostly migraine or probable migraine, is the most common symptom following TBI with between 15 - 91% of people (depending on patient population, e.g. athlete, veteran) reporting migraine-like symptoms. Those reporting migraine are likely to have a longer recovery period and a greater impairment. Finally, having a personal history of migraine prior to TBI, may predispose a person to concussion, intensify symptoms of concussion and slow-down recovery.
Endometriosis (a gynaecological disease, where endometrium-like tissue grows outside the uterus) occurs in an estimated 7-10% of women of reproductive age. Migraine affects an estimated 15-18% of women, mostly between the ages of 18-49 (i.e. their reproductive years). Both conditions are influenced by hormones and both conditions present with a variety of severity, although the underlying cause of endometriosis is unknown.
Endometriosis has been consistently found to be more common among women who live with migraine. When both conditions are present, migraine attacks are more frequent and disabling; and pelvic pain is also more severe. In their meta-analysis, Jenabi, E., & Khazaei, S. (2020), suggested that pain and proinflammatory chemicals along with CGRP are activated in both conditions which have an effect on the central nervous system, ultimately leading to central sensitisation – hypersensitivity to pain. Other mechanisms at play include dysfunction of the serotonergic system (pain modulating system) and mast cells (pain producing cells).
Early menarche (starting periods before 11 years) among young women with endometriosis appears to be a risk factor for migraine; however when endometriosis is NOT present, there is no greater risk for migraine.
Finally, Tietjen, G.E., et al (2007), after comparing groups of women who had both migraine and endometriosis to those who had migraine but not endometriosis, found that those with both conditions, had a higher risk of other comorbid conditions.
Migraine and epilepsy are comorbid conditions, with epilepsy usually occurring first. Migraine (mostly migraine with aura) has been found to occur in 8-24% of people with epilepsy. Whereas, epilepsy has been found among 5-9% of migraine patients. Rates of both conditions increase when they are the result of head trauma (Rogawski, MA., 2012). The two conditions do not cause one another (if they did, far more people would live with both conditions); rather migraine and epilepsy share some common mechanisms. While migraine rarely triggers a seizure, in the post-seizure period of an epileptic attack, migraine-like headache is common.
- Migraine and epilepsy attacks go through similar stages: prodrome, aura, attack, postdrome and interictal (between attack) phase.
- While both epilepsy and migraine attacks often include an aura phase, caused by cortical spreading depression (CSD), in epilepsy this lasts a few seconds, but in migraine, it is much longer.
- At times, attacks cannot be stopped resulting in status epilepticus or status migrainosus.
- Both migraine and epilepsy share a number of common triggers; e.g. stress; sleep disturbances; photophobia; hormonal changes; diet and/or alcohol.
- Antiepileptic drugs (AEDs) such as divalproex sodium (valproate) and topiramate, are used in the prevention of both conditions by reducing neuronal hyperexcitability (increased activity in brain neurons), which adds evidence that they share common underlying mechanisms.
- Finally, such medication therapy (AEDs) proves non-efficacious in about 30% of people with either migraine or epilepsy.
- It is thought that in both conditions there is a fault in the electro-chemical signalling system which makes them more susceptible to otherwise harmless stimuli.
- Both conditions share some common genes.
Although the two conditions share a number of similar underlying mechanisms, it is unknown why some people will have migraine, some epilepsy, and some both.
Fibromyalgia and chronic pain
Fibromyalgia is a chronic pain condition that presents with widespread musculoskeletal pain, fatigue, “brain fog”, sleep, memory and mood issues; all symptoms which overlap with migraine. Other types of chronic pain conditions include lower back pain, arthritis, multiple sclerosis, shingles, nerve damage and of course, migraine.
When people experience chronic pain, including fibromyalgia, for long periods, changes occur in how the brain processes pain. This is known as “central sensitisation”, which plays a role both in fibromyalgia and chronic migraine. Other factors which may be part of the cause of both migraine and fibromyalgia are genetic predisposition, neurophysiological changes, and abnormal stress response.
Studies have found that between 18% - 36% of people with migraine, also experience fibromyalgia or another chronic pain condition (Whealy, et al., 2018). Such people report increased headache related disability, depression and headache severity. In other words, they have a severely impacted quality of life. Sadly, in a study by Liu,et al., 2015, the authors found that migraine with comorbid fibromyalgia was a predictor of suicidal ideation and attempts, particularly for those with migraine without aura, migraine with aura, and chronic migraine.
Migraine with comorbid fibromyalgia or chronic pain conditions can be treated similarly to other comorbid conditions such as anxiety and depression. Namely, patients should take an active role in their treatment which could include: gentle exercise (e.g. yoga, tai chi); good health practices (healthy diet, good sleep routines); and a holistic approach to the management of their conditions, combining non-pharmacologic and other individual pharmacologic treatment (e.g. some antidepressants, which can be helpful in managing pain).
Irritable Bowel Syndrome (IBS) and other functional bowel disorders
Gastrointestinal (GI) disorders in patients with migraine are more common than in the general population. On the other hand, chronic headache has been reported in 34%-50% of all IBS patients. Helicobacter pylori infection, irritable bowel syndrome (IBS), gastroparesis, coeliac disease (CD) and alterations in the microbiota are all linked to migraine. A number of mechanisms involving the gut-brain axis, such as a chronic inflammatory response and dysfunction of the autonomic and enteric nervous system, among others, are thought to explain these associations.
When seeking treatment, it is worthwhile to consider both conditions as some GI disorders may affect how you respond to migraine treatments; e.g. gastroparesis may affect how well your body absorbs oral medications and an alternative route may be more suitable.
For some patients, diet modifications might be beneficial, not only for their GI disorder, but also for migraine; e.g. a gluten-free diet for those with CD; dietary approaches with beneficial effects on gut microbiota and gut-brain axis including increased fibre; following a low glycaemic index diet, supplementation with vitamin D, omega-3 and probiotics as well as weight loss for overweight and obese patients.
Insomnia and other sleep disorders
Sleep disorders are three times more common among people living with migraine than among the general population. Over a third of migraine patients report frequent sleep difficulties, chronic short sleep and sleep disorders (including obstructive sleep apnoea (OSA), periodic limb movement disorder (including restless leg syndrome), bruxism (teeth grinding), circadian rhythm disorder, insomnia, and hypersomnia).
The relationship between sleep and migraine works both ways – migraine makes sleep more difficult and sleep disorders make migraine worse. Treating the sleep disturbance can have a beneficial effect on migraine; at times even a reversal from chronic to episodic. On the other hand, for those living with migraine, who also engage in shift work or have regularly broken or poor-quality sleep, there is a possibility that episodic migraine may develop into the chronic form.
Ménière’s disease, benign paroxysmal positional vertigo (BPPV) and other balance disorders
Ménière’s disease is a chronic condition of the inner ear, which occurs with a set of symptoms including: dizziness or vertigo, at times with nausea and imbalance; and muffled hearing, tinnitus (ringing in ears) and / or hearing loss. It usually occurs in people aged between 40 and 60 years old. Like some forms of migraine, it can be preceded by an aura phase and like migraine, it can be associated with other conditions such as anxiety.
Benign Paroxysmal Positional Vertigo (BPPV) is the most common balance disorder. People may experience a sense of dizziness and / or spinning; light-headedness, unsteadiness, loss of balance and nausea which occur with movements of the head; e.g. getting out of bed or rolling over; or raising the head to look up at the ceiling.
Large scale epidemiological studies have, as yet, not been able to establish a clear link between Ménière’s disease and migraine. For example, an epidemiological study of 423,400 individuals found the prevalence of migraine in the population to be 3.8% and found the incidence of migraine in patients with Ménière syndrome to be approximately 4.5% - which was not significantly elevated (Gopen et al., 2009). However, smaller-scale studies have found very significant relationships between the two conditions, especially when patients are interviewed. A study by Ray et al. (2016) of 181 patients with both Ménière’s disease and other balance disorders found that patients with Ménière’s Disease were more likely to have a history of migraine, compared with patients who had other balance disorders (45.1% versus 9%). Another study that compared 78 patients with age and sex-matched controls found migraine with and without aura was significantly higher in the group with Ménière’s disease (56%) compared to the control group (25%) (Radtke et al., 2002).
There is an established relationship between BPPV and migraine, though the direct pathophysiological link remains unclear. A study of 476 patients with BPPV found 54.8% had a history of migraine, three times more than the general population (Uneri, 2004). Hilton et al.’s (2020) study of 1481 patients with BPPV also found a higher rate of migraine, with 25.8% self-reporting a history of migraine. Additionally, of those patients who had migraine and BPPV, 88.5% were female. Faralli et al.’s (2014) study of 186 patients diagnosed with migraine also found a higher prevalence of BPPV, as well as earlier onset of BPPV, but they found that a direct pathophysiological link between migraine and BPPV is unlikely.
There is some difficulty in distinguishing many balance disorders that may be comorbid with migraine, from vestibular migraine — which may result in balance-related symptoms such as dizziness or vertigo. However, there is evidence to suggest that balance disorders and migraine are comorbid conditions. For example, motion sickness has been found to be more prevalent in patients with migraine, with studies finding rates of between 30-70%, compared with control groups who reported 20-40% (Lempert & Neuhauser, 2009). A German study by von Brevern et al. (2008) also found an epidemiological link between migraine and dizziness in a representative phone survey (n=7341).
Multiple sclerosis (MS) is a chronic disease of the central nervous system where the covering of nerve fibres is are damaged, so nerve signals from the brain and spinal cord to other parts of the body are affected. Some of the symptoms of MS overlap with the symptoms of migraine; e.g. tiredness, dizziness, problems with concentration, and changes in mood.
Multiple Sclerosis (MS) and migraine are comorbid neurologic conditions in the sense that migraine is three times higher in the MS population compared to the general population. Patients with MS and migraine have more severe symptoms (cognitive, psychiatric, brainstem and visual symptoms, depression, anxiety and fatigue) than patients with MS but without migraine, according to work by Kister, I. et al., (2010). Such people are also more likely to experience a more progressive, relapsing form of MS. However, the authors suggest that having a family history of migraine, and hence a predisposition to the condition, rather than MS initiating migraine, is significant.
To explain the worsening symptoms of MS patients with migraine, the authors suggested the role of more severe brain inflammation which occurs with migraine, altered pain perception and central sensitisation. Cortical spreading depression (the mechanism behind aura) is likely to exacerbate symptoms.
Obesity and overweight
The relationship between migraine and obesity is complicated. Yes, it has been found that both total body obesity (TBO), measured by body mass index (BMI), and abdominal obesity (AO) are associated with a higher prevalence and frequency of migraine when compared to headache-free individuals, especially among those under 50 years old. However, there are puzzles which aren’t covered by that blanket statement.
Obesity defined by BMI doesn’t distinguish between fat and muscle tissue, or between abdominal and peripheral fat distribution. Using waist circumference might be a better and more meaningful measure of abdominal fat; but most past studies have not used this.
The tissue in abdominal obesity produces multiple substances potentially involved in migraine pathophysiology, including markers of systemic inflammation, some of which (e.g. adiponectin and leptin) are elevated in people with migraine even in the interictal (between acute attack) phases. Other chemicals, such as serotonin, function as appetite regulators and are linked to obesity as well as migraine.
Both fat distribution and migraine prevalence vary considerably with sex and age - where fat tends to be deposited differs among men and women and also by age. These differences of age and sex can also affect the relationship between them; e.g. there is little or no association between obesity and migraine among older individuals, but there is a significant association in younger women of child-bearing age. Interestingly TBO rather than AO, may be a risk factor for chronification.
Other mechanisms which may have a role in the relationship between the two conditions are:
- Biological – inflammation, cardio-metabolic
- Psychological – depression, anxiety, pain acceptance
- Lifestyle – diet, physical activity, sleep
Given that obesity and migraine both increase the risk of cardiovascular disease, weight loss is recommended for people who experience both conditions. It is understood that for some experiencing frequent migraine attacks, exercise may exacerbate symptoms. Even so, the benefits of maintaining a healthy weight are beneficial for migraine, obesity and general health and wellbeing.
Patent foramen ovale (PFO)
Patent foramen ovale (PFO) is a congenital (about 15-25% of people can be born with it) heart defect, where there is a passageway between the right and left upper chambers (atria) of the heart. Clots can form or move between the 2 parts of the heart eventually causing stroke, TIA, or aura-like episodes. Results from studies vary considerably about the numbers of people with migraine along with PFO
Although it is possible that migraine is a risk factor for stroke because of a PFO, and some people may benefit from PFO closure, clinical trials of PFO closure have not proven that this is an effective way to prevent migraine (Tariq N, Tepper SJ, Kriegler JS., 2016).
Postural orthostatic tachycardia syndrome (PoTS)
Postural orthostatic tachycardia syndrome (PoTS), also known as Postural tachycardia syndrome, is a disorder of that part of the nervous system which manages things that we don’t consciously control (e.g. heart rate, blood pressure and body temperature); i.e. the autonomic nervous system. PoTS presents with a number of symptoms (some of which overlap with migraine), but the defining feature is that symptoms such as significant heart rate increase and dizziness, are present within the first 10 minutes of standing up.
In medical practices, up to 90% of PoTS patients report headache, mostly migraine as described by Cortez, M. M., Millsap, L., & Brennan, K. C. (2021). To blur the situation, migraine presents with autonomic dysfunction such as allodynia (sensitivity to touch) and photophobia (sensitivity to light) which worsen as severity of attacks increase - a risk for chronification. It has been proposed that these features are clinical markers of central sensitization which is present in both PoTS and chronic migraine. These overlapping features and central sensitization imply that there are common physiological pathways underlying each condition; although these pathways work differently in the two conditions.
Strokes typically occur after the age of 50. However, there is increasing evidence that having migraine is associated with an increased risk of stroke (ischaemic stroke, haemorrhagic stroke and cardiovascular disease in general), particularly for women under 45 years old, with high frequency, late onset migraine with aura, use of oral contraceptives and smoking (Øie, L. R., Kurth, T., Gulati, S., & Dodick, D. W., 2020); although the overall risk is still low. The relationship between the two (migraine with its sub-types and stroke with its sub-types) is not yet fully understood, although reasons for the connection include unfavourable vascular risk factors; the role of ‘cortical spreading depression’ (electrophysiological mechanism underlying migraine aura); and shared genetic overlap. Hemiplegic migraine often mimics stroke and for which there is a known genetic basis. Some of the ways in which the two conditions may be connected include:
- Migraine can be a risk factor for stroke. If other stroke risk factors are added ( e.g. high blood pressure, smoking, diabetes, use of high dose oestrogen contraceptive pill, high cholesterol, heavy drinking, high salt and high fat diet and lack of exercise), the risk of stroke also increases.
- Migraine may be caused by stroke (symptomatic migraine)—ischemia or haemorrhage could trigger a migraine-like, or aura-like event.
- Migraine and stroke may share a common cause e.g. an abnormality of blood vessels (known as vasculopathy); a rare example of this would be the genetic condition, Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy (CADASIL).
- Migraine is associated with “silent stroke” (asymptomatic cerebral infarction) which doesn’t produce any symptoms of stroke, but may show-up on an MRI.
Currently, there is no definitive confirmation that migraine prophylactics can reduce future stroke risk in people with migraine. So, it is suggested that people with migraine with aura and risk of stroke take extra care with their medications and lifestyle. An example would be to avoid the abortive migraine medications such as ergotamine and triptans which both can constrict blood vessels. However, Lee, M. J., Lee, C., & Chung, C. S. (2016) reported that, “stroke rarely occurs in migraine patients who do not abuse ergots or triptans in the absence of contraindication”. Management and reducing all risk factors is the preferred preventative approach; i.e. not smoking, staying active, not abusing alcohol, and controlling weight, blood pressure, blood sugar and cholesterol.
Migraine, when it occurs with any comorbid conditions becomes even more complex and disabling. Some people may have more than one comorbid condition or any combination of conditions. It is important to recognise and understand each individual situation.
Understanding each individual’s situation and the medical conditions they live with is significant in the care of complex medical situations, from initial diagnosis through effective treatment to minimising the burden that individuals face in their daily lives. Understanding the comorbidities that come with migraine is also important for the understanding of disease pathophysiology and genetics. – The more that is known, the better the outcome.
Arzani, M., Jahromi, S. R., Ghorbani, Z., Vahabizad, F., Martelletti, P., Ghaemi, A., Sacco, S., Togha, M., & School of Advanced Studies of the European Headache Federation (EHF-SAS) (2020). Gut-brain Axis and migraine headache: a comprehensive review. The journal of headache and pain, 21(1), 15. https://doi.org/10.1186/s10194-020-1078-9
Bainomugisa, C.K., Sutherland, H.G., Parker, R., Mcrae, A.F., Haupt, L.M., Griffiths, L.R., Heath, A., Nelson, E.C., Wright M.J., Hickie, I.B., Martin, N.G., Nyholt D.R., Mehta, D. (2021). Using Monozygotic Twins to Dissect Common Genes in Posttraumatic Stress Disorder and Migraine. Frontiers in Neuroscience, 15, 758. https://doi.org/10.3389/fnins.2021.678350
Bigal, M. E., Kurth, T., Santanello, N., Buse, D., Golden, W., Robbins, M., & Lipton, R. B. (2010). Migraine and cardiovascular disease: a population-based study. Neurology, 74(8), 628–635. https://doi.org/10.1212/WNL.0b013e3181d0cc8b
Buse, D. C., Reed, M. L., Fanning, K. M., Bostic, R., Dodick, D. W., Schwedt, T. J., Munjal, S., Singh, P., & Lipton, R. B. (2020). Comorbid and co-occurring conditions in migraine and associated risk of increasing headache pain intensity and headache frequency: results of the migraine in America symptoms and treatment (MAST) study. The journal of headache and pain, 21(1), 23. https://doi.org/10.1186/s10194-020-1084-y
Cámara-Lemarroy, C. R., Rodriguez-Gutierrez, R., Monreal-Robles, R., & Marfil-Rivera, A. (2016). Gastrointestinal disorders associated with migraine: A comprehensive review. World journal of gastroenterology, 22(36), 8149–8160. https://doi.org/10.3748/wjg.v22.i36.8149
Cortez, M. M., Millsap, L., & Brennan, K. C. (2021). Synergistic but separable sensory changes in postural tachycardia syndrome and chronic migraine. Clinical autonomic research : official journal of the Clinical Autonomic Research Society, 31(2), 263–271. https://doi.org/10.1007/s10286-020-00740-y
Faralli, M., Cipriani, L., Del Zompo, M. R., Panichi, R., Calzolaro, L., & Ricci, G. (2014). Benign paroxysmal positional vertigo and migraine: analysis of 186 cases. B-ENT, 10(2), 133–139.
Gopen, Q., Viirre, E., & Anderson, J. (2009). Epidemiologic study to explore links between Ménière syndrome and migraine headache. Ear, Nose, & Throat Journal, 88(11), 1200–1204.
Hilton, D. B., Luryi, A. L., Bojrab, D. I., Babu, S. C., Hong, R. S., Bojrab, D. I., Santiago Rivera, O. J., & Schutt, C. A. (2020). Comparison of associated comorbid conditions in patients with benign paroxysmal positional vertigo with or without migraine history: A large single institution study. American Journal of Otolaryngology, 41(6), 102650. https://doi.org/10.1016/j.amjoto.2020.102650
Jahangir, S., Adjepong, D., Al-Shami, H. A., & Malik, B. H. (2020). Is There an Association Between Migraine and Major Depressive Disorder? A Narrative Review. Cureus, 12(6), e8551. https://doi.org/10.7759/cureus.8551
Jenabi, E., & Khazaei, S. (2020). Endometriosis and migraine headache risk: a meta-analysis. Women & health, 60(8), 939–945. https://doi.org/10.1080/03630242.2020.1779905
Kascakova, N., Furstova, J., Hasto, J., Madarasova-Geckova, A., & Tavel, P. (2020). When a head is about to burst: Attachment mediates the relationship between childhood trauma and migraine. International journal of environmental research and public health, 17(12), 4579. https://doi.org/10.3390/ijerph17124579
Kister, I., Caminero, A. B., Monteith, T. S., Soliman, A., Bacon, T. E., Bacon, J. H., Kalina, J. T., Inglese, M., Herbert, J., & Lipton, R. B. (2010). Migraine is comorbid with multiple sclerosis and associated with a more symptomatic MS course. The journal of headache and pain, 11(5), 417–425. https://doi.org/10.1007/s10194-010-0237-9
Kristoffersen, E. S., Børte, S., Hagen, K., Zwart, J. A., & Winsvold, B. S. (2020). Migraine, obesity and body fat distribution - a population-based study. The journal of headache and pain, 21(1), 97. https://doi.org/10.1186/s10194-020-01163-w
Kuo, F. H., Lee, C. Y., Li, J. P., Chung, J. F., Wang, Y. H., Hsieh, M. J., & Yang, S. F. (2020). Migraine as a risk factor for peripheral artery occlusive disease: A population-based cohort study. International journal of environmental research and public health, 17(22), 8549. https://doi.org/10.3390/ijerph17228549
Kurth, T., Winter, A. C., Eliassen, A. H., Dushkes, R., Mukamal, K. J., Rimm, E. B., Willett, W. C., Manson, J. E., & Rexrode, K. M. (2016). Migraine and risk of cardiovascular disease in women: prospective cohort study. BMJ (Clinical research ed.), 353, i2610. https://doi.org/10.1136/bmj.i2610
Lau, C. I., Lin, C. C., Chen, W. H., Wang, H. C., & Kao, C. H. (2015). Increased risk of chronic fatigue syndrome in patients with migraine: A retrospective cohort study. Journal of psychosomatic research, 79(6), 514–518. https://doi.org/10.1016/j.jpsychores.2015.10.005
Lee, M. J., Lee, C., & Chung, C. S. (2016). The Migraine-Stroke Connection. Journal of stroke, 18(2), 146–156. https://doi.org/10.5853/jos.2015.01683
Lempert, T., & Neuhauser, H. (2009). Epidemiology of vertigo, migraine and vestibular migraine. Journal of Neurology, 256(3), 333–338. https://doi.org/10.1007/s00415-009-0149-2
Lipton, R. B., Fanning, K. M., Buse, D. C., Martin, V. T., Reed, M. L., Manack Adams, A., & Goadsby, P. J. (2018). Identifying natural subgroups of migraine based on comorbidity and concomitant condition profiles: results of the chronic migraine epidemiology and outcomes (CaMEO) study. Headache, 58(7), 933–947. https://doi.org/10.1111/head.13342
Liu, H. Y., Fuh, J. L., Lin, Y. Y., Chen, W. T., & Wang, S. J. (2015). Suicide risk in patients with migraine and comorbid fibromyalgia. Neurology, 85(12), 1017–1023. https://doi.org/10.1212/WNL.0000000000001943
Mehle M. E. (2012). Migraine and allergy: a review and clinical update. Current allergy and asthma reports, 12(3), 240–245. https://doi.org/10.1007/s11882-012-0251-x
Minen, M. T., Begasse De Dhaem, O., Kroon Van Diest, A., Powers, S., Schwedt, T. J., Lipton, R., & Silbersweig, D. (2016). Migraine and its psychiatric comorbidities. Journal of neurology, neurosurgery, and psychiatry, 87(7), 741–749. https://doi.org/10.1136/jnnp-2015-312233
Minen, M.T., Weissman, J., Tietjen, G.E., (2019). The Relationship Between Migraine or Severe Headache and Chronic Health Conditions: A Cross-Sectional Study from the National Health Interview Survey 2013–2015, Pain Medicine, Volume 20, Issue 11, November 2019, Pages 2263–2271, https://doi.org/10.1093/pm/pnz113
Øie, L. R., Kurth, T., Gulati, S., & Dodick, D. W. (2020). Migraine and risk of stroke. Journal of neurology, neurosurgery, and psychiatry, 91(6), 593–604. https://doi.org/10.1136/jnnp-2018-318254
Peterlin, B. L., Nijjar, S. S., & Tietjen, G. E. (2011). Post-traumatic stress disorder and migraine: epidemiology, sex differences, and potential mechanisms. Headache, 51(6), 860–868. https://doi.org/10.1111/j.1526-4610.2011.01907.x
Prudenzano, M. P., Monetti, C., Merico, L., Cardinali, V., Genco, S., Lamberti, P., & Livrea, P. (2005). The comorbidity of migraine and hypertension. A study in a tertiary care headache centre. The journal of headache and pain, 6(4), 220–222. https://doi.org/10.1007/s10194-005-0190-1
Radtke, A., Lempert, T., Gresty, M. A., Brookes, G. B., Bronstein, A. M., & Neuhauser, H. (2002). Migraine and Ménière's disease: is there a link?. Neurology, 59(11), 1700–1704. https://doi.org/10.1212/01.wnl.0000036903.22461.39
Rainero, I., Govone, F., Gai, A., Vacca, A., & Rubino, E. (2018). Is Migraine primarily a metaboloendocrine disorder?. Current pain and headache reports, 22(5), 36. https://doi.org/10.1007/s11916-018-0691-7
Ray, J., Carr, S. D., Popli, G., & Gibson, W. P. (2016). An epidemiological study to investigate the relationship between Meniere’s disease and migraine. Clinical Otolaryngology: Official Journal of ENT-UK ; Official Journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery, 41(6), 707–710. https://doi.org/10.1212/01.wnl.0000036903.22461.39
Rogawski MA. Migraine and epilepsy—shared mechanisms within the family of episodic disorders. In: Noebels JL, Avoli M, Rogawski MA, et al., editors, (2012). Jasper's basic mechanisms of the epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US). https://www.ncbi.nlm.nih.gov/books/NBK98193/
Tietjen, G.E., Bushnell, C.D., Herial, N.A., Utley, C., White, L. and Hafeez, F. (2007), Endometriosis Is associated with prevalence of comorbid conditions in migraine. Headache: The Journal of Head and Face Pain, 47: 1069-1078. https://doi.org/10.1111/j.1526-4610.2007.00784.x
Rains, J. C., & Poceta, J. S. (2006). Headache and sleep disorders: review and clinical implications for headache management. Headache, 46(9), 1344–1363. https://doi.org/10.1111/j.1526-4610.2006.00578.x
Seifert T. (2018). The relationship of migraine and other headache disorders to concussion. Handbook of clinical neurology, 158, 119–126. https://doi.org/10.1016/B978-0-444-63954-7.00012-4
Smitherman, T. A., & Kolivas, E. D. (2013). Trauma exposure versus posttraumatic stress disorder: relative associations with migraine. Headache, 53(5), 775–786. https://doi.org/10.1111/head.12063
Tariq N, Tepper SJ, Kriegler JS. (2016). Patent Foramen Ovale and migraine: closing the debate-a review. Headache. Mar;56(3):462-78.https://doi.org/10.1111/head.12779
Timm, F.P., Houle T.T., Grabitz, S.D., et al. (2017). Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ;356: i6635. doi: 10.1136/bmj.i6635
Trivedi M., Dumkrieger, G., Chong, C., Dodick, D., Schwedt, T., (2021). Impact of abuse on migraine symptoms and comorbidity: results from the American registry for migraine research (ARMR), Abstract to be presented at the American Academy of Neurology’s 73rd Annual Meeting, April 17-22, 2021. https://index.mirasmart.com/AAN2021/PDFfiles/AAN2021-002187.html
Uneri, A. (2004). Migraine and benign paroxysmal positional vertigo: an outcome study of 476 patients. Ear, Nose, & Throat Journal, 83(12), 814–815. https://doi.org/10.1177/014556130408301211
von Brevern, M., Radtke, A., Lempert, T., & Neuhauser, H. (2008). Population-based epidemiological evidence for the link between dizziness and migraine. Aktuelle Neurologie, 35(S 01), P623. https://doi.org/10.3233/VES-2011-0423
Wang, L., Deng, Z. R., Zu, M. D., Zhang, J., & Wang, Y. (2021). The Comorbid relationship between migraine and asthma: a systematic review and meta-analysis of population-based studies. Frontiers in medicine, 7, 609528. https://doi.org/10.3389/fmed.2020.609528
Whealy, M., Nanda, S., Vincent, A., Mandrekar, J., & Cutrer, F. M. (2018). Fibromyalgia in migraine: a retrospective cohort study. The journal of headache and pain, 19(1), 61. https://doi.org/10.1186/s10194-018-0892-9