What Are the Comorbidities of Migraine? 2023
The word “comorbidity” refers to a greater than coincidental association of two conditions in the same individual.
It means that two medical problems occur together in the same patient more likely than by chance. Migraine is a common medical problem and for women, is the most prevalent illness women have. Twenty percent of women and six percent of men have migraine.
The most painful conditions are a kidney stone, pregnancy, and a migraine headache. Migraine is the fifth most prevalent disabling condition and the tenth most frequent reason for a visit to the emergency room.
Migraine headache consists not only of severe, usually one-sided headache, but also of sensitivity to light, odors, and sound. Migraine turns on the brain stem generator for nausea and makes a person nauseated or vomit. Migraine makes a person want to be still and lie down, usually in a dark, quiet room, rather than be up and about.
If one had Migraine it would be nice to know other medical disorders that relate to it. The medical conditions that link to migraine are discussed below.
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This is an article by Britt Talley Daniel MD, retired member of the American Academy of Neurology, the American Headache Society, migraine textbook author, and blogger.
List Of Migraine Comorbidities:
1.Respiratory conditions
The main entries are allergic rhinitis and asthma which have a 17% link to migraine.
Allergic rhinitis is commonly called by the man on the street “sinus” or “hay fever.” “Rhino” refers to the nose; think of rhinoceros here, and allergic refers to a genetically inherited condition of over-reaction of the immune system to foreign antigens, like cedar pollen, or cat dander.
A common lay idea is that a medical condition exits called “allergy headache.” But this is mistaken, and the word “allergy” is not even listed in the index of the 3rd International Classification of Headache.
Allergic symptoms can aggravate migraine indirectly, but there is no direct allergic pathophysiologic mechanism causing headache.
An allergic reaction is an antigen-antibody reaction, where the antigen is a foreign protein like cedar pollen and the antibody is another complex protein made by the immune system.
This reaction causes mast cells to release histamine and histamine causes most of the allergic symptoms of itchy, red, swollen eyes, nasal congestion, sneezing, production of clear nasal fluid, and tearing. This relates to an allergic condition.
The release of internal neurochemicals of CGRP, Neurokinin A, and Substance P from the arterial and trigeminal nerve ganglia occurs during a migraine headache. These neurochemicals inflame the cerebral arteries, the trigeminal nerve, and the brain pain center, the thalamus, resulting in a severe migraine headache. This relates to migraine.
Many different chemicals cause vasodilation and therefore aggravate migraine headache. This is why MSG, chocolate, tyramine in aged cheese, and nitrates in hot dogs may aggravate migraine.
There is a relationship between the ingestion of such a chemical and headache, but the headache comes because of vasodilation caused by the offending chemical (i.e. chocolate) but not from an allergic reaction (antigen/antibody reaction, mast cell release of histamine.)
Thus if a patient is suffering from severe allergic symptoms and is stressed by these symptoms, not sleeping well, and feeling lousy at work, AND if they have inherited the migraine gene, they may have, indirectly, more migraines, but there is no direct relationship between allergic rhinitis and migraine.
Asthma has a lifetime prevalence with Allergic rhinitis of 50% to 100% among adults with asthma in Europe and in the United States. Asthma has a strong link to psychiatric problems, such as depression, generalized anxiety disorder, and post-traumatic stress disorder.
With migraine the cerebral arteries dilate, but with asthma the small lung bronchioles constrict leading to reduced oxygen passage and producing the characteristic and diagnostic asthmatic symptom of an inspiratory wheeze as air tries to pass through a narrow tubular passage.
Adrenalin type inhalers used to treat asthma may also produce anxiety and panic like symptoms.
2.Cardiovascular diseases.
Stroke, particularly ischemic cerebral infarction, is increased with migraine with aura by 6 %. This risk may be aggravated by taking an estrogen-based birth control treatment such as a pill or patch.
Hypertension is one of the most common risk factors for development of atherosclerotic (hardening and narrowing of the arteries). Hypertension has a 10 % link to migraine. Hypertension can relate to the anxiety disorders also.
Angina/myocardial infarction. Angina is chest related or arm, chin, back, or neck referred pain that comes with exertion or anxiety. Angina relates to heart disease. It’s the man in Minnesota who shovels snow in his driveway for 10 minutes and gets chest pain.
Angina may be stable and not by itself that serious if the chest pain clears with nitroglycerin, but angina establishes the patient has organic heart disease.
Chest pain is always serious and should be thoroughly evaluated as relating to the heart, but if the patient has been examined by a cardiologist and had appropriate testing, he may be given nitroglycerin, a coronary artery dilating medication, to take for his chest pain.
Angina doesn’t mean heart attack, but it is hard to separate them and important to know whicht it is. Stable heart disease with angina can be treated with a vasodilator like nitroglycerin.
The precise biological mechanism by which migraine with and without aura may increase the risk of myocardial infarct is currently unknown but statistically relevant.
Raynaud’s Disease and Raynaud’s Phenomenon are associated with migraine. Raynaud’s phenomenon and Disease are neurovascular symptoms relating to constriction and dilatation of small arteries.
It is a sensitive reaction to temperature change of exposure usually to cold, but also to heat, and emotional events, whereby a person’s fingers and toes tingle and then turn white-red-and then blue.
Raynaud’s Disease is associated with and may be a marker of autoimmune medical problems such as lupus erythematosus, or rheumatoid arthritis, while Raynaud’s phenomenon is more benign and occurs without association with other medical problems and is benign.
Migraine is another disorder involving vasoconstriction and dilation of cerebral arteries.
Congenital Heart Disease. A recent study found an increase in the prevalence of migraine among adults with congenital heart disease. The frequency of migraine was highest among congenital heart disease subjects with right-to-left shunt (52%) followed by those with left-to-right shunt (44%).
Mitral Valve Prolapse Mitral is a common heart condition found in 1.5 to 2% of the population, and in most persons does not cause symptoms. It results from descent of part of the mitral valve, on the left side of the heart, between the small chamber (atrium) and the large chamber that pumps blood to the body (ventricle).
Mitral valve prolapse symptoms are chest pain, rapid heartbeat, and anxiety. The relationship between migraine and mitral valve prolapse is uncertain, yet the association has been reported.
Patent foramen ovale (PFO) is found in as many as 25% of persons early in life, and usually spontaneously closes on its own. Yet, patent foramen ovale may extend into adulthood and be associated with migraine.
In many individuals (as many as 25% or more), however, the foramen ovale may persist unclosed (patent) into adulthood. A number of studies have suggested that individuals with migraine are more likely to have a patent foreman ovale (PFO), and this association is most evident in those whose attacks of migraine may be accompanied by aura.
The means by which a patent foramen ovale may relate to migraine is not understood, yet there is a statistical relationship between the two. Most of the literature has clustered around PFO and migraine with aura.
One theory is that blood components which are normally screened in the lungs, would pass through an open PFO to the brain and thereby activate migraine.
Surgical closure of a PFO has been associated with reduction of migraine with aura in some patients, and currently transfemoral catheterization closure of a PFO is considered to be a viable part of treatment for stroke and migraine prevention.
Atrial septal defect (ASD) is statistically related to migraine, yet like PFO, surgery to close the defect is not medically indicated.
3.Endocrinological
Hypothyroidism is statistically related to migraine and treatment of hypothyroidism lowers the severity and frequency of migraine attacks. Migraine patients should have their thyroid profile studied.
4.Dermatological
Psoriasis is related to multiple medical comorbid conditions including cardiovascular disease (stroke, ischemic heart disease, congestive heart failure, hypertension) and metabolic disorders (dyslipidemia, obesity, insulin resistance, and type 2 diabetes).
Psoriasis also relates to migraine although how psoriasis increases the risk of migraine is uncertain. One theory is that a link between psoriasis and migraine may be due to endothelial inflammation and nervous system involvement.
5.Gastrointestinal
GI disorders have an increased frequency in patients with migraine compared with the general population.
Helicobacter pylori infection, irritable bowel syndrome, gastroparesis, hepatobiliary disorders, celiac disease and alterations in the microbiota have been linked to the occurrence of migraine.
Several mechanisms involving the gut-brain axis, such as a chronic inflammatory response with inflammatory and vasoactive mediators passing to the circulatory system, intestinal microbiota modulation of the enteric immunological milieu and dysfunction of the autonomic and enteric nervous system, have been postulated to explain these associations.
However, the precise mechanisms and pathways related to the gut-brain axis in migraine are not fully understood, yet there is a large literature linking migraine to GI disease.
Irritable bowel syndrome, (IBS), is one of the most GI problems with a relationship with migraine, present in 60% of IBS patients. Migraine and IBS also strongly link to psychiatric disorders such as chronic insomnia, generalized anxiety disorder, and depression.
A research study showed that chronic headaches were reported by 30% of the people with celiac disease, 56% of those who were gluten sensitive, 23% of those with inflammatory bowel disease, and 14% of those without the conditions.
Persons with celiac disease, gluten sensitivity, and inflammatory bowel disease all have more migraine headaches than people without these conditions.
6.Rheumatologic
Fibromyalgia links to migraine with a 17% comorbidity rate. Both conditions have been found to cause central sensitization, which means inflammation of the main brain pain center, the thalamus. Both migraine and fibromyalgia can cause allodynia, which is a condition whereby touch, which is not usually perceived as painful, is found to be painful.
Allodynia is found with stage four of the migraine timing cycle with chronic migraine due to medication overuse headache. It is due to central sensitization because the central nervous system trigeminal nucleus and cutaneous scalp fibers are inflamed.
After a sunburn, touch of the involved skin area hurts. The touch fibers in the skin of the back and shoulders are inflamed by the burning of the sun. Wearing a shirt or a jacket over a sunburned shoulder or arm would be perceived as painful, not as just touch.
Touch of one side of the head during a migraine may also hurt, as the pain sensory fibers are activated. Activities that may cause pain with allodynia are combing or brushing the hair, wearing a hat, earrings, a necklace, glasses, or lying in bed on the involved side of the head.
All of these “touch” activities may hurt in a person who has allodynia related to medication overuse headache or fibromyalgia.
Chronic migraine has also been shown to increase episodes of pain in people with fibromyalgia, among other symptoms such as high frequency of headache, sleep disturbances and anxiety.
Light, noise, and touch can act as triggers for both fibromyalgia and migraine.
Fibromyalgia and migraine are commonly co-morbid disorders. There is a high prevalence of fibromyalgia in migraineurs and a high prevalence of migraine and other headaches in patients with fibromyalgia.
Studies have found reports of increased headache related disability, depression, and headache severity in patients with comorbid fibromyalgia and migraine as compared to those with migraine only.
The presence of fibromyalgia has been correlated with lower quality of life in patients with migraine, making it important to screen for symptoms of fibromyalgia in the migraine population.
7.Neurologic
Epilepsy. Migraine and epilepsy are comorbid, episodic, paroxysmal neurologic disorders. The prevalence of epilepsy is 0.5% and of migraine is 12%. Six percent of patients with migraine have epilepsy and 8-15% of patients with epilepsy have migraine.
A migraine aura may trigger a seizure an hour later (migralepsy) and a seizure may trigger a migraine attack.
Research published in Epilepsia in 2013 first investigated the role of genetics in the co-occurrence of migraine and epilepsy. The results showed that a history of migraine with aura was “significantly increased in enrolled participants with two or more additional affected first-degree relatives,” supporting the hypothesis of a shared genetic susceptibility to migraine and epilepsy.
Migraine and Epilepsy may both be treated with neuronally active drugs such as Depakote, Topamax, and gabapentin which says something about the relationship of the inherent brain abnormality of both conditions.
Tension-type headache has been found in multiple research studies to be associated with epilepsy.
Multiple Sclerosis Migraine occurs 2 to 3 times more frequently in patients with MS than the general population. Clinical overlap between migraine and MS has been recognized since 1952, when a study by McAlpine and Compston observed that 2% of patients with MS developed migraine within 3 months of an initial relapse.
A higher overall prevalence of migraine in MS has since been supported by multiple controlled and uncontrolled studies reporting rates between 21% and 69%.
8.Psychiatric
Mood disorders
Depression may link to migraine 50% of the time and is the most common of associated psychiatric conditions in patients with migraine.
Depressive symptoms may be:
Mood: anxiety, apathy, general discontent, guilt, hopelessness, loss of interest or pleasure in activities, mood swings, or sadness
Behavioral: agitation, excessive crying, irritability, restlessness, or social isolation
Sleep: early awakening, excess sleepiness, insomnia, or restless sleep
Whole body: excessive hunger, fatigue, or loss of appetite
Cognitive: lack of concentration, slowness in activity, or thoughts of suicide
Weight: weight gain or weight loss
Poor appetite or repeatedly going over thoughts
Depressive disorders occur in patients with partial complex seizure disorders of temporal and frontal lobe origin.
Depression is more common in poorly controlled epilepsy and may precede the later development of seizures.
Animal models of epilepsy show decreased activity of serotonin, norepinephrine, dopamine, and GABA which facilitates the kindling process of seizure foci, worsen seizure frequency and severity, and are reversed or blocked by antidepressant drugs.
Dysphoria regarding epilepsy, described as intermittent dysphoric disorder,(IDD), between seizures, was first described by Emil Kraepelin in 1923 and consist of as set of symptoms found in 17% of people with chronic epilepsy.
Dysphoria is from the Greek: (δύσφορος dysphoros, δυσ-, difficult, and φέρειν, to bear) is a profound state of unease or dissatisfaction. In a psychiatric context, dysphoria may accompany depression, anxiety, or agitation.
The most common symptom of intermittent dysphoric mood disorder is intermittent dysphoric mood in between seizures. Interictal dysphoric disorder can often be treated with a combination of antidepressant and anticonvulsant medication.
Symptoms may be: depressive moods, irritability, anergia, insomnia, pains, phobic fears, and euphoric moods. The diagnosis of IDD should be made when at least three of the eight symptoms are present.
Bipolar disorder, (BD), used to be called “manic/depressive disorder” and it consists of alternating mood states of mostly being mildly or severely depressed or down alternating with times of mild or severe mania.
Between 25 and 40 percent of people who have bipolar disorder also have migraines.
The exact reason for this is not known but it is thought that certain aspects of brain chemistry are the same for migraines and bipolar disorder.
Migraine drugs such as Depakote, Topamax, and gabapentin are helpful for bipolar disorder also.
Generalized anxiety disorder, (GAD) affects everybody on earth. We all have some degree of stress or anxiety. Some might not be able to talk about it or identify it, but the experience of anxiety is universal.
GAD has an increase of migraine, likely related to genetic brain relationship or insomnia.
The number one trigger for a migraine headache is stress which relates to anxiety.
Half of persons with insomnia have GAD, the most common cause of sleeplessness.
GAD symptoms:
Excessive anxiety and worry
Difficult to control
Several subjects
Symptoms occur for more days than not for six months
Significant distress or social impairment
At least three ancillary symptoms
Ancillary Symptoms
Restlessness/mental tension
Fatigability
Poor concentration
Irritability
Muscle tension-in neck, shoulders, jaw, or teeth, grinding or bruxism
Sleep disturbance
One German study of focal epilepsy and anxiety disorders revealed:
social phobia, 7.2%
specific phobia, 6.2%
panic disorder, 5.1%
generalized anxiety disorder, 3.1%
anxiety disorder not further specified, 2.1%
obsessive–compulsive disorder, 1.0%
post-traumatic stress disorder, 1.0%).
Panic disorder
A panic attack is an abrupt surge of intense fear or intense discomfort that reaches a peak within minutes, and during which time four (or more) of the following symptoms occur: Four panic symptoms are required by the Diagnostic and Statistical Manual of Mental Disorders 4th Edition, (DSMD 4).
Panic disorder is characterized by sudden, brief episodes of physical and mental symptoms which, by definition, occur spontaneously or “out of the blue,” to differentiate it from anxiety attacks that have never occurred spontaneously and have always been secondary to a specific reason.
For anxiety attacks the patient should have insight or a reason as to why the event occurred. Anxiety would come after a sudden attack by an assailant who wanted to kill you. There would be an evident reason for the symptoms resulting from such an attack. This is not true with panic disorder. Both panic attacks and anxiety turn on the brain’s “fight or flight” mechanism.
Palpitations, pounding heart, or accelerated heart rate
Sweating
Trembling or shaking
Sensations of shortness of breath or smothering
Feeling of choking
Chest pain or discomfort
Nausea or abdominal distress
Feeling dizzy, unsteady, lightheaded, or faint
Chills or heat sensations
Paresthesias (numbness or tingling sensations)
Derealization ( feelings of unreality) or depersonalization (being detached from oneself).
Fear of losing control of “going crazy.”
Fear of dying.
One or two panic attacks is called panic attack but more than 3 panic attacks is called panic disorder.
Many people with panic disorder will experience a migraine headache right after having a panic attack. This may be called simultaneous occurrence of a panic attack and a migraine. Many of these patients with panic symptoms of tingling on one side of their body or chest pain may get frightened and go to the emergency room.
The ER will usually check vital signs and do an ECG to be sure there is no heart disease and do a brain CAT scan to rule out hemorrhage or tumor. Then the patient will often be referred later by the ER to see a cardiologist and a neurologist.
Persons with panic disorder have more severe and frequent migraines.
Risk factors for occurrence of panic disorder and migraine are being female, having co-occurring agoraphobia, and depression.
The prevalence of migraine in one anxiety disorder clinic sample was 67%. Anxiety disorder patients with migraine presented with a significantly greater number of comorbid psychiatric disorders than patients without migraine.
Read my mini neurology textbook on “Panic Disorder” as an eBook or print. Click here to buy.
Agoraphobia The incidence of agoraphobia with migraine is low since agoraphobia incidence is only 2% in the US.
Panic disorder and agoraphobia often occur together. Agoraphobia is anxiety in which the affected person may fear and avoid places or situations that might cause panic symptoms or make the person feel trapped, helpless or embarrassed.
The lifetime prevalence of agoraphobia in the general US population is about 2%, with 1 study showing a higher prevalence (10.4%) in adults older than 65 years.
Despite its high prevalence in older adults, the average age of onset of agoraphobia is actually between ages 25 and 30 years.
Agoraphobia is twice as common in women and is also more disabling in women compared with men.
During their lifetimes, 87.3% of individuals with agoraphobia will also meet criteria for another psychiatric disorder, including panic disorder, social anxiety disorder, specific phobia, generalized anxiety disorder (GAD), and substance use disorder.
Chronic fatigue Syndrome (CFS), is very common with persons with migraine. One study from researchers at Georgetown University found migraine in 84% of patients with CFS.
The breakdown was 60% had migraine without aura and 24% had migraine with aura. Tension-type headaches were present in 81% of CFS sufferers.
Obsessive-compulsive disorder, one of the anxiety disorders, has not been well studied with
migraine. One study found that migraine patients with medication overuse headache had more obsessive-compulsive symptoms.
Obsessive–compulsive disorder (OCD) belongs to the anxiety spectrum disorders and may be a comorbid condition in patients with migraine. OCD seems to occur at higher frequency in patients with migraine than in the general population, but little information regarding this association is available
Attention Deficit Disorder, (ADD) and Attention Deficit Hyperactive Disorder, (ADHD) have an increased prevalence of migraine compared to controls from the general population.
This is due to co-morbidity between these two disorders of the brain, possibly related to their shared underlying pathophysiologies and co-morbidities with other neuropsychiatric disorders, like mood and anxiety disorders.
In general, roughly one in five adults with ADHD will experience migraines, and the condition is more common in women than in men.
One study found that migraine was strongly associated with ADHD. There was a significant interaction between age and gender, with comorbidity increasing with age and female sex . Post-hoc analysis showed that migraine with visual disturbance was generally associated with a marginally higher risk of ADHD and this was independent of ADHD endophenotypes.
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All the best.
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Britt Talley Daniel MD
