Alice-in-Wonderland Syndrome

Alice-in-Wonderland Syndrome is a rare neurological condition that can temporarily cause changes in visual perception, an altered sense of time as well as sensory and hearing abnormalities. When occurring comorbidly with migraine, the condition typically begins in childhood prior to the diagnosis of migraine. A migraine attack may occur before or after the Alice-in-Wonderland symptoms occur. This condition may be related to migraine with aura.

Clinical studies indicate about 15% of patients with migraine may also have the syndrome.^1,2  

Allergic Rhinitis

Allergic rhinitis is a reaction that is caused after an exposure to an allergen which provokes an immune response. Then, inflammation develops within the nose causing congestion, runny nose, post nasal drip and sneezing. Allergic rhinitis can occur seasonally or perennially (year round). Common allergens are dust, pollen, pet dander and mold which may trigger migraine attacks for some people.

A study found that migraine was 14.3 times more likely among those with allergic rhinitis compared to a control group.¹

In addition, allergic rhinitis can cause sinus headaches. “It was seen that among patients with sinus headache referred to otolaryngology clinics, up to 75% may have histories compatible with the migraine criterion.”²

Alzheimer’s Disease

Alzheimer’s Disease is a progressive neurological condition characterized by loss of cognitive function, including memory and behavioral abilities. It is the most common cause of dementia. Researchers believe Alzheimer’s is caused by brain cell damage due to abnormal structures called plaques and tangles.

A study found that those with migraine were three times more likely to develop Alzheimer’s Disease, especially women.¹ 

Anxiety

Anxiety is a mental health disorder that is associated with excess fear and worry and interferes with daily life activities for six months or greater. Diagnostic symptoms according to DSM-5 must include three of the following: restlessness, sleep disturbances, fatigue, impaired concentration, irritability and muscle tension, without attribution to another cause.¹

"Anxiety disorders are two to five times more prevalent in patients with migraine than in the general population, up to two times more common in patients with migraine than in patients with depression, and much more common in patients with CM than in patients with EM."²

Arthritis

Arthritis is a musculoskeletal condition that causes inflammation of the joints. It results in pain, stiffness, decreased range of motion and swelling in the joints. Arthritis symptoms such as sleep disturbances, neck pain, stress are often triggers of migraine.¹ Additionally, people with arthritis may frequently use analgesics which can cause rebound headache. Inflammation may be a key component of the link between arthritis and migraine. 

Jacob et. al found "a positive and significant arthritis–migraine relationship in the overall sample, in women, in adults aged ≤45 years, and in those aged >65 years."¹

Asthma

Asthma is a respiratory disease that causes a persons airway to become inflamed and narrowed, resulting in wheezing, coughing, and difficulty breathing. Overexertion, breathing cold air or exposure to certain allergens are common triggers of an asthma attack.

In a study of 288 asthma patients,  60.4% complained of a headache and 32.6% of subjects met the IHS criteria for migraine.¹ 

Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder (ADHD) is a mental health condition that includes at least one of three distinguishing behaviors: inattention, hyperactivity and impulsivity. ADHD can interfere with development and/or functioning. It often begins in childhood and can extend throughout adulthood. Comorbid mood disorders are common among those with ADHD and migraine.

In one study 28.3% of the 572 subjects with ADHD also had migraine, whereas 19.2% of the 675 subjects without ADHD in the control group had comorbid migraine.¹ 

Back pain

Acute back pain affects over 65 million Americans and 16 million live with chronic back pain.¹ Acute back pain occurs for less than three months and chronic back pain occurs for greater than three months. The lower back, also known as the lumbar region, is most commonly affected.

A study found those with primary headache (migraine and or frequent tension type headache or chronic tension type headache) were 1.7 times more likely to also have low back pain. ² 

Bell’s Palsy

Bell's Palsy is a condition associated with dysfunction in the facial nerve that results in facial paralysis and/or weakness (usually on one side). The exact cause is unknown, however it is thought to be related to a viral infection. Bell's Palsy is usually temporary, occurring for six months or less but can become permanent in some people.

A study found that those with migraine had a 1.28 times higher risk of Bell's Palsy compared to controls in those who were ≥30 and <60 years old.¹

Bipolar Disorder

Bipolar disorder is a mental health condition that affects 2.1% of the global population. It is characterized by drastic mood changes ranging from depression to hypomania and mania. Manic episodes may cause insomnia, racing thoughts and high energy. Mania may lead to risky and/or reckless behavior. Hypomania occurs for a shorter time and is less severe than mania symptoms. Depression is a low energy state, often resulting in feelings of sadness, withdrawal from others and loss of self worth.

“Patients suffering from migraine with aura are three times more likely to suffer from bipolar disorder than the general population. Conversely, about one-third of patients with bipolar disorder have migraine.”¹

Celiac Disease

Celiac disease is an autoimmune condition that causes an inflamed small intestine after eating gluten containing foods. Symptoms include bloating or gas, constipation, diarrhea, fatigue/tiredness, irritability, itchy skin rash, joint pain and poor weight gain. Those affected by celiac disease must avoid foods that contain wheat, rye and barley. Gluten and histamines may be migraine triggers for some people.

A study of 118 people with celiac disease found that those with celiac disease had a higher rate of chronic headaches compared to controls.¹ 

Central Auditory Processing Disorder

Central Auditory Processing Disorder (CAPD) occurs when the brain has trouble interpreting sounds. For an unknown reason, the ears and brain don't fully communicate. A person may mishear similar sounds and words and may be unable to determine similar sounds in a noisy environment or block out background noise.

A study looking into CAPD and migraine found that both patients with migraine and vestibular migraine had performed worse on central auditory testing than controls.¹

Chiari Malformation

Chiari Malformation is a structural defect that typically occurs during fetal development but may also occur due to drainage of excessive spinal fluid. Normally, the cerebellum lies above the opening to the skull (also known as the foramen magnum). With Chiari malformation, the cerebellum extends below the foramen magnum and into the spinal canal. There are four types of Chiari malformation with type 1 being the most prevalent.

A study of 73 patients with Chiari Malformation Type 1 (CM-1) 11% had chronic migraine, which is almost 3 times the rate in the general population.¹ 

Chronic Bronchitis

Bronchitis is an inflammation of the bronchioles, or tubes, that carry air into the lungs. When inflammation occurs, a person can experience cough, wheezing and excess mucus in the lungs. Acute bronchitis lasts 10-14 days and is typically caused by a viral infection while chronic bronchitis lasts for 3 months or greater. Chronic bronchitis is common in smokers. 

“Both migraine and nonmigrainous headache were approximately 1.5 times more likely among those with current asthma, asthma related symptoms, hay fever, and chronic bronchitis than those without. The association increased with increasing headache frequency.”¹

Chronic Kidney Disease

Chronic kidney disease (CKD) is the loss of kidney function over a period of time. The kidneys play a vital role in making hormones as well as filtering waste, toxins and extra water. They also help create red blood cells, balance minerals and electrolytes and maintain bone health. Two main causes of CKD are diabetes and hypertension. Chronic kidney disease can progress into end stage kidney failure which can be fatal without dialysis or a kidney transplant. 

A study found that those with migraine had a 1.22 times higher risk of having CKD compared to controls.¹ Additionally, they found that those who took propranolol or NSAIDS for migraine were also at higher risk of CKD.¹ 

Complex Regional Pain Syndrome

Complex Regional Pain Syndrome (CRPS) is a rare neuroinflammatory disorder that causes extreme pain in an arm or leg after an injury or nerve trauma. It can be acute (less than six months) or chronic (greater than six months). Like migraine, CRPS is a disabling condition, more common among women and does not have a definitive diagnostic test. Migraine and CRPS also share many psychological comorbidities such as anxiety, depression and bipolar disorder.

Peterlin et.al found that "those with CRPS were 3.6 times more likely to have migraine and nearly twice as likely to have chronic daily headache as the general population."¹

COVID-19/Long-Haul COVID

COVID-19 has affected millions of people worldwide and has caused more than 5.3 million deaths as of December 2021.¹ Headache is the most common neurological symptom among those infected with COVID-19.²  This infectious virus usually causes mild symptoms which may include: cough, headache, fever, chills, congestion, muscle and/or body aches as well as loss of taste and/or smell. Some people experience severe complications such as respiratory failure, systemic inflammatory response syndrome (SIRS) and death.

A survey of those who developed COVID-19 found approximately one third of COVID-19 associated headaches occurred in those who had a previous history of migraine.³

Cyclic Vomiting Syndrome

Cyclic Vomiting Syndrome (CVS) is a disorder where a person experiences recurrent attacks of nausea and vomiting that may last hours to days with an unknown etiology. The attacks usually last for the same length of time and occur at the same time of day; most often late night to early morning. One third of children may have cyclic vomiting syndrome and/or abdominal migraine in childhood followed by migraine disease in adulthood.¹

“Studies have shown that 39–87% of children with CVS and 24–70% of adults with CVS have a migraine association based upon either a positive family history or concomitant or subsequent development of migraines in the patient.”¹

Dementia

Dementia is not a disease but is an overarching term used to describe symptoms such as memory loss, loss of cognitive function, decreased social abilities, and mood changes that are severe enough to interfere with daily life. Alzheimer's, Vascular, and Lewy Body are examples of diseases that cause dementia.

A study found a 50% higher rate of dementia among individuals with migraine than those without.¹ “Individuals without aura had a 19% higher rate of dementia, and individuals with aura had a two times higher rate of dementia.¹

Depression

Depression is a mood disorder that results in profound feelings of sadness, hopelessness and loss of self worth. It often causes loss of interest and pleasure in activities, fatigue and changes in sleep. In order to consider a diagnosis of depression, symptoms must persist for two weeks or greater. A healthcare provider should be notified about any mood changes. Depression and migraine have a bidirectional relationship and share common pathophysiology, treatments and relations to other comorbidities.

“Three different studies found that migraineurs are over 2.5 times more likely to suffer from depression compared with non-migraineurs.”¹

Ehlers-Danlos syndromes

The Ehlers-Danlos syndromes are a group of connective tissue disorders that mainly affect the joints and skin. Different genes have been tied to the production of faulty collagen. The type of Ehlers-Danlos Syndrome one gets depends on where the defective collagen/connective tissue is in their body. Connective tissue is located throughout the body, in the bones, ligaments, between organs and tissues, joints, etc. therefore presentation of this syndrome may vary. One key feature of this condition is that people typically experience hypermobility of joints. Migraine and Ehlers-Danlos syndrome both occur more frequently in women and share comorbid conditions such as fibromyalgia, postural orthostatic tachycardia syndrome (POTS) and irritable bowel syndrome.

A study concluded that people with Ehlers-Danlos syndrome and migraine experience more frequent migraine days, more accompanying symptoms and a higher rate of disability.¹  Migraine tends to start earlier in those who also have Ehlers-Danlos syndrome.

Endometriosis

The endometrium is a tissue that lines the inside of the uterus and is shed during each menstrual cycle. Endometriosis is a gynecological condition characterized by growth of endometrial-like tissue outside of the uterus and is associated with immune dysfunction as well as inflammation. Its growth is stimulated by estrogenic female hormones. The tissue can be found in or around the intestines, rectum, ovaries, fallopian tubes, the bladder, pelvic cavity, etc. Women will present with symptoms such as dysmenorrhea (painful periods), dyspareunia (pain with intercourse), GI symptoms, pelvic pain and infertility.

A study found that migraine was 1.7 times more common in women with endometriosis than in those without the disease and a majority of the women experienced migraine after their endometriosis diagnosis rather than before their diagnosis (78.8% vs. 21.2%).¹

Epilepsy

Epilepsy is a neurological condition that occurs when a person has two or more seizures that are not attributable to another cause. There are many commonalities among those who have migraine and epilepsy including symptomatology, genetics and pathophysiology.

According to Liao et. al (2018), the risk of patients who have idiopathic epilepsy getting migraine with aura is roughly double. Accordingly, patients with migraine also increased the risk of getting epilepsy.¹

Erectile Dysfunction

Erectile Dysfunction (ED) is characterized by the inability to produce and/or maintain an erection. Many causes of erectile dysfunction are comorbid with migraine such as heart disease, Multiple Sclerosis, Parkinson’s disease and more.

A study in Medicine 2016 found the overall incidence of ED was 1.78 times greater in the migraine group than in the control group.¹ Furthermore, patients with migraine were 1.75 times more likely to develop ED from a physical cause (medication side effects, vascular issues, etc.) rather than psychological.¹ 

Fibromuscular dysplasia

Fibromuscular dysplasia (FMD) is a disease that causes narrowing, beading, bulging (aneurysm) and dissections in the medium to large arteries in the body. Headaches and ringing in the ears are two of the most common symptoms reported in FMD patients.

“Headaches, mainly of the migraine type, are observed in up to 70% of patients with FMD.”¹

Genes such as PHACTR1 have also been associated between FMD and migraine. 

Fibromyalgia

Fibromyalgia is a chronic condition that causes widespread pain throughout the body, primarily affecting muscles, bones and joints. Individuals experience a hypersensitivity to both painful and non-painful stimuli. Migraine disease and fibromyalgia are both disabling conditions frequently coexisting together and share a bidirectional relationship, especially in women.

Studies have found that 20-36% of those with migraine disease also have fibromyalgia and 45-80% of those with fibromyalgia also have migraine.¹

Gastric Ulcer/Gastrointestinal Bleed (GIB)

A gastric ulcer develops when the naturally occurring gastric acid damages the protective barrier (mucosa) of the stomach resulting in an open sore. Common causes of a gastric ulcer are frequent usage of anti-inflammatory medications, stress, acidic foods and a bacteria known as H.Pylori. A complication from a gastric ulcer is a gastrointestinal bleed.

In the MAST study, people with migraine were 3.11 times more likely to report gastric ulcers/GI bleeding.¹

Gastroparesis

Gastroparesis is defined as delayed emptying of solids and liquids from the stomach into the small intestine without evidence of a blockage. This causes nausea, vomiting and abdominal pain and many of these symptoms overlap with migraine. A study found that stomach emptying was delayed in people with migraine.¹ Delayed gastric emptying and vomiting can affect the absorption and efficacy of migraine medications.¹ 

Another study found that out of 511 people with gastroparesis 36.6% reported having migraine attacks.¹ 

Glaucoma

Primary open angle glaucoma (POAG) is an eye condition caused by a reduced drainage in the eye canals due to blocked canals. This results in increased eye pressure which causes damage to the optic nerve. This condition is one of the leading causes of irreversible blindness.

Although a definitive link has not been identified between primary open angle glaucoma and migraine, a meta-analysis concluded “subjects who suffered from migraine had a 24% higher risk of developing POAG when compared to those who had never suffered from migraine.”¹

Gulf War Illness

Gulf war illness is an unexplained condition that affects veterans who served in the Persian Gulf War from 1990-1991. Veterans may experience a wide range of symptoms such as fatigue, chronic pain, memory problems, respiratory illnesses, headaches, migraine and more.

According to a study, 64% of Gulf War veterans had migraine compared to 13% of controls.

Headache After Stroke

It is important to note that headache and/or migraine disease may occur after having a stroke, depending on the location and the severity of the stroke.

A new onset headache during the ischemic stroke can raise the risk of having persistent headaches post-stroke which can lead to significant disability.¹

Helicobacter pylori (H.pylori)

H. Pylori is a bacteria that can cause an infection in the stomach and the small intestine. It commonly causes inflammation of the stomach as well as peptic ulcer disease. H. Pylori infections can lead to certain types of stomach cancer. A meta analysis was conducted to determine if there was a relationship between migraine and H.Pylori.

The study found that there is a positive connection between migraine and H.Pylori (44.97% compared to 33.26% in the control group ).¹

Other studies found that once the infection was treated, migraine attacks significantly reduced. 

Hemorrhagic Stroke

During a hemorrhagic stroke, a weakened artery ruptures and causes bleeding within the brain or in the tissue surrounding the brain. This leads to increased pressure and swelling in the brain. The area of the brain affected will be deprived of oxygen rich blood.

“Sacco et.al (2013), found the risk of hemorrhagic stroke increased by 50% in subjects with any migraine compared with nonmigraineurs."¹

Hyperlipidemia

Hyperlipidemia, often referred to as high cholesterol, is having high levels of fats in the bloodstream such as cholesterol and triglycerides. Hyperlipidemia can be caused by a familial genetic disorder or from eating too many foods high in saturated fat.

A study found that those who had high triglycerides were 3.11 times more likely to have migraine compared to controls.¹ Those with high cholesterol were 17.14 times more likely to have migraine disease compared to controls.¹

Hypertension

Hypertension is also known as high blood pressure. Blood pressure is the force of blood pushing on the walls of the arteries. Normal blood pressure is less than 120 /80. The first number, known as the systolic blood pressure, represents the pressure in the blood vessels when the heart beats. The second number is the diastolic blood pressure representing the pressure in the vessels when the heart rests in-between beats. When blood pressure exceeds 130/80 it is considered stage 1 hypertension. Stage 2 hypertension is blood pressure greater than 140/90. Elevated blood pressure commonly occurs due to atherosclerosis, stress, smoking, unhealthy diets and inactivity.

In the MAST study, those with severe headache intensity had a higher risk of hypertension. Additionally, after adjusting for socio-demographics, those with migraine were 1.51 times (50%) more likely to have hypertension than those in the non-migraine group.¹

Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension is characterized by high pressure in the skull due to build up of cerebrospinal fluid that occurs due to an unknown reason. The increase in fluid puts pressure on the brain causing a wide range of symptoms such as double vision, blind spots, dizziness, nausea, headaches, tinnitus and vision loss.

In a study of 68 patients with idiopathic intracranial hypertension, forty-five patients (63.2%) met the diagnostic criteria for migraine.¹ 

Insomnia

Insomnia is a sleep condition that occurs when someone experiences difficulty falling asleep or staying asleep, or has a combination of both. This results in daytime fatigue, irritability and memory impairment. Some people may experience acute insomnia which occurs for less than a few weeks compared to chronic insomnia which occurs for greater than three nights a week for three months or longer. It is likely that migraine and insomnia have a bidirectional relationship. Insomnia is a risk factor for migraine onset, pain intensity and chronification and those with migraine are at increased risk of developing insomnia.¹

A study found a higher prevalence of insomnia in people with migraine (25.9%) compared to those without migraine (15.1%).¹

Interstitial Cystitis

Interstitial cystitis is a chronic urological condition that causes pain and pressure in the bladder in the absence of a urinary tract infection. There are two subtypes of interstitial cystitis: nonulcerative and ulcerative and symptoms range from mild to severe. Most people will experience frequent urination, dyspareunia, a constant urge to urinate and pelvic pain.

A study found that 18% of those with interstitial cystitis also had migraine.¹

Interstitial cystitis shares many common comorbid conditions with migraine such as irritable bowel syndrome, systemic lupus erythematosus, endometriosis and more.

Irritable Bowel Syndrome

Irritable Bowel Syndrome (IBS) is considered a functional gastrointestinal condition affecting the large intestine. Those with IBS may have diarrhea, constipation or a mix of both with abdominal pain and/or cramping. IBS symptoms can be brought on by factors such as stress, changes in gut microbiome, intestinal nerve issues, infection and more. Both migraine and IBS are conditions occurring more often in women and share other comorbidities such as depression and fibromyalgia. Both conditions affect the gut-brain-axis which could be a plausible connection between the comorbidities. 

Studies have found those with migraine have a high prevalence of IBS ranging from 4% to 40%.”¹

Ischemic Stroke

An ischemic stroke, the most common type of stroke, occurs when an artery in the brain becomes blocked due to a blood clot. This causes decreased blood flow to an area of the brain and absence of oxygen and nutrients which causes brain cells to die.

The Journal of Neurology, Neurosurgery and Psychiatry found that the relative risk of ischemic stroke is doubled in people who have migraine with aura compared to migraine-free individuals.¹

Joint Hypermobility Syndrome

Joint Hypermobility Syndrome (JHS) is a connective tissue disorder that causes hypermobility of joints (abnormally large range of motion/movement) and may be confused with Ehler Danlos Syndrome and Marfan’s Syndrome. According to Rheumatology Advisor, Marfan syndrome and Ehlers-Danlos syndrome are connective tissue disorders with multisystem manifestations.¹. Joint hypermobility Syndrome commonly affects the musculoskeletal system and results in recurrent injuries, dislocations, sprains and stiffness.

A study of 28 women with joint hypermobility syndrome and 232 female controls participated in a case-cohort study and the results indicated that migraine prevalence was 75% in JHS patients and 43% in controls.²

Keloid

A keloid is an overgrowth of scar tissue that forms when there is excess collagen during the healing process of a skin injury. Common injuries where keloids form are from burns, piercings, acne and surgical incisions. They are often raised, hairless and hard. They can be itchy or have a burning sensation but are usually painless.

A study found that the overall migraine risk was 2.29 times greater in the keloids cohort compared with a non-keloid cohort after adjustment for age, gender and relevant comorbidities.¹

Risk factors for migraine in the keloid group were stroke, fibromyalgia, insomnia, anxiety, asthma and female gender, which are all comorbid with migraine.¹

Mal de Débarquement syndrome

Mal de Débarquement syndrome is a condition that causes someone to feel like they are still moving after being on a boat, plane, car or train, etc. The feeling usually resolves within 24 hours but is classified as persistent when it lasts greater than one month.

The prevalence of migraine in those with Mal de Débarquement syndrome was 23% in motion triggered individuals and 38% in non-motion triggered subjects (passive motion that occurred less than 2 hours).¹

Marfan Syndrome

Marfan syndrome is a genetic connective tissue disorder that can affect almost every system in the body. Connective tissue has an important role to support, protect and give structure to parts of the body. Types of connective tissue are ligaments, cartilage, bone, and fat tissue. Marfan syndrome can cause damage to the heart, blood vessels, lungs, skin as well as bone abnormalities and much more.

A study of 309 Marfan Syndrome patients and 102 controls found 40% of those with Marfan Syndrome had migraine compared to 28% of the controls.¹ Migraine with aura was found in 22% of those with Marfan Syndrome compared to 14% of controls.¹

Meniere’s disease

Meniere’s disease is an inner ear disorder that primarily affects one ear. It is caused by fluid buildup in the inner ear, resulting in vertigo, tinnitus, a feeling of fullness in the ear and/or hearing loss. Meniere’s Disease has similar triggers, treatments and symptoms as migraine, especially vestibular migraine.

A study found up to 51% of individuals with Meniere’s Disease experiencing migraine compared to 12% in the general population.¹

Mitral Valve Prolapse

The mitral valve is on the left side of the heart, between the left atrium (top part of the heart) and left ventricle (bottom part of the heart). Normally, the valve opens and pushes blood from the top part of the heart to the bottom which contracts to distribute blood to the whole body. During mitral valve prolapse (MVP) the mitral valve abnormally slips backwards into the top part of the heart (left atrium). Symptoms may include an irregular heartbeat, palpitations, fatigue and shortness of breath. Similar to migraine, this condition is more common in women and those with connective tissue disorders.

"A study of 230 MVP patients found that 27.8% had migraine, a proportion significantly larger than that expected in the general population. Nearly 30% of the migraineurs had migraine with aura."¹

Multiple Sclerosis

Multiple sclerosis is an autoimmune disease that affects the central nervous system. The immune system attacks the protective coating of nerves (known as the myelin sheath). The demyelination leads to nerve damage causing profound neurological symptoms.

A study that assessed the relationship between migraine and MS found that among 204 MS patients, the relative frequency of migraine was three times higher than in the non-MS population controls both for men and women.¹

The study also found that pain related conditions such as trigeminal neuralgia, facial pain, TMD joint pain and restless leg syndrome were 2-5 times higher in those who had MS and migraine compared to those without.¹ All of the pain related conditions listed are also comorbid with migraine disease.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Chronic fatigue syndrome/Myalgic Encephalomyelitis (CFS/ME) is a complex and debilitating multi-system, chronic disease that causes extreme, persistent fatigue and flu-like symptoms that lasts greater than six months. The key symptom of ME/CFS is post-exertional malaise (PEM), the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. Other symptoms include unrefreshing sleep, brain fog, orthostatic intolerance, photophobia, GI abnormalities and headache. Many of these symptoms overlap with migraine.

In one study, migraine and tension headache were found to be prevalent in 84% and 81% of the CFS subjects, respectively, compared to 5% and 45% of those in the control group.¹

Myocardial Infarction (Heart Attack)

Myocardial infarction (MI), also known as a heart attack, occurs when there is an obstruction of blood flow to the heart. This results in ischemia or cell death as the heart is starved of oxygen and other necessary nutrients. A person typically experiences chest pain, dizziness, pain down the arm or into the jaw, fatigue, nausea and more. These signs and symptoms warrant immediate medical attention. 

A study found that myocardial infarction occurred in 1.9% of controls vs 4.1% of people with migraine.

Narcolepsy

Narcolepsy is a neurological disorder that causes inability to have normal patterns of being awake and asleep. People with narcolepsy can experience excessive daytime sleepiness, sudden sleep, sleep paralysis, hallucinations and in some cases loss of muscle control (also known as cataplexy). These symptoms can cause impairment of daily activities due to the inability to stay awake.

A study in Cephalgia (2003) found migraine prevalence 44.4% in women with narcolepsy and 28.3% in men with narcolepsy.¹

Obesity

Obesity is classified as a body mass index greater than 30 and was prevalent among 42.4% of Americans from 2017-2018.¹ There is variability among studies examining the correlation between migraine and obesity.

Women with migraine were about 11% more likely to become overweight or obese in one study and another study found that there is a 40% increased risk for women to have migraine if they were obese.²

Weight loss has been associated with a decrease in headache days demonstrating a positive correlation between migraine and obesity. 

Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a sleep condition that occurs when the airway is intermittently narrowed or blocked throughout the night, resulting in decreased oxygen saturation levels. Snoring is a key symptom of OSA along with headache and daytime fatigue. Clinical trials did not find migraine and OSA to be comorbid. Although, a clinical trial did note for those who have both conditions, treatment with continuous positive airway pressure or CPAP improved migraine burden.¹ Studies found up to 80% of people with cluster headache also live with OSA.² In addition, headache prevalence among those with OSA ranges from 32.9-58.5%³, most commonly presenting with tension headache. Another type of chronic headache, known as a “sleep apnea headache” occurs greater than 15 days a month, usually in the morning without hypersensitivities to light, sound, or other migraine-type symptoms. 

Approved Migraine Research for 2022

Dr. Eric Gruenthal is a sleep medicine fellow at the Cleveland Clinic. His research was recently approved by AMD's Research Advisory Committee and is awaiting funding from AMD.

In an interview with AMD, Dr. Gruenthal was asked how his research will lead to a better understanding of migraine conditions.

He responded by saying:

"The project will foster a more detailed understanding of the causal nature between sleep disorders (especially sleep-disordered breathing, such as obstructive sleep apnea) and migraine, and address the question of whether proven therapies for sleep-disordered breathing (specifically positive airway pressure) also improve migraine outcomes, such as migraine frequency and intensity."

Osteoarthritis

Osteoarthritis is a musculoskeletal condition that occurs when the cartilage, found at the end of the bone, wears down over time. Once the cartilage wears away, the bones rub against each other. This can cause significant pain and unfortunately there is no cure. This condition is more common in women, the elderly and those who are overweight. 

The MAST study found an 1.35 times increased risk of osteoarthritis in those who have severe headache pain.¹ 

Osteoporosis

Osteoporosis (which means “porous bone”) causes bones to become fragile or weak. According to the Mayo Clinic, osteoporosis occurs when the creation of new bone doesn't keep up with the loss of old bone.¹

A study found the overall incidence of migraine was 1.37 times higher among those with osteoporosis and those especially at risk were females, those with comorbid hypertension, depression, asthma, allergic rhinitis, obesity and tobacco use disorder.² 

Parkinson’s Disease

Parkinson’s Disease is a neurodegenerative disorder where nerve cells die in a part of the brain known as the substantia nigra. These nerve cells produce a neurotransmitter called dopamine. When the nerve cells die, dopamine production is decreased. The reduction of dopamine causes abnormal motor symptoms such as tremors, stiff muscles, coordination problems and slow movement but can also cause non-motor issues such as sleep problems, constipation, pain, urinary problems and more.

A study assessing the prevalence of migraine in 237 Parkinson’s Disease subjects found that 27.8% had migraine within their lifetime.¹ In addition, after the onset of Parkinson’s Disease, two thirds had improvement in their migraine attacks or complete remission.¹ 

Patent Foramen Ovale

The foramen ovale is a hole located between the top two chambers of the heart of fetuses. Normally, within the year after birth the hole closes but for some people it stays open and is known as patent (open) foramen ovale. This hole between the upper chambers of the heart (atria) results in abnormal blood flow from the right side of the heart to the left. Migraine and patent foramen ovale are both risk factors for stroke.

“Later, a number of studies found that the incidence of PFO in migraine patients was 14.6-66.5% while the incidence in the general population was 9-27.3%.”¹

Periodic Limb Movement Disorder

Periodic Limb Movement Disorder (PLMD) is a sleep condition distinguished by repeated twitching or jerking movements of the legs and feet during sleep. It can occur every 5 to 90 seconds for minutes to hours. PLMD and migraine share comorbidities such as restless leg syndrome and insomnia.

A study that looked at PLMD and migraine in children suggested that PLMD could influence migraine, increasing its severity, frequency and all disabling aspects and also treatment efficacy.¹

Peripheral Artery Disease

Peripheral arterial disease refers to a circulatory impairment that causes narrow blood vessels in the extremities resulting in decreased blood flow. The most common cause of this condition is atherosclerosis, where fat and plaque builds up in the arteries. Most people will have a variety of symptoms, mostly occurring in their legs such as pain while walking, numbness, cool extremities and a pale or bluish discoloration. 

The MAST study’s migraine group was at least twice as likely to experience peripheral artery disease.¹ The study also found that those who had 5-9 monthly headache days were at an increased risk for peripheral artery disease compared to those who had 1-4 headache days per month.¹  

Phantom Dental Pain

Phantom dental pain is a neuropathic pain condition where a person feels pain in their mouth or face when no physical condition is causing it. It is often a persistent throbbing or aching that can begin after a nerve injury or dental procedure. It is believed to be due to nerve endings sending signals to the person’s brain telling it that it feels pain.¹ A tooth extraction is an example where people feel pain although the tooth is no longer there. 

A study examining the relationship between headache disorders and phantom dental pain distributed a questionnaire to 50 cluster headache patients and 251 migraine without aura patients as well as 280 people in a control group.² The study found that found 15% (46/301) of the people with headache disorders also had phantom dental pain.²

Further looking at the results, 20% (10/50) of cluster headache patients and roughly 14% (36/251) of the migraine without aura patients had phantom dental pain.² No subjects in the control group had phantom dental pain.²

Post Traumatic Stress Disorder

Post traumatic stress disorder (PTSD) is a mental health condition where a person experiences recurrent feelings of intense fear, helplessness and/or horror following a traumatic event. Two to three times more women experience both PTSD and migraine than men.¹

PTSD is more prevalent in those living with migraine than in the general population (14–25% vs 1–12%).²

Postural Orthostatic Tachycardia Syndrome (POTS)

Postural Orthostatic Tachycardia Syndrome (POTS) is a disorder of the autonomic nervous system. A person may experience challenges when moving to an upright position due to an increase in heart rate and accompanying symptoms.

A study of 41 subjects with POTS found that 39 subjects had a history of headache. "Chronic migraine (CM) was diagnosed in 25 (61%), episodic migraine (EM) in 12 (29%), new persistent daily headache in 1 patient, and orthostatic headache in 1 patient."¹

Psoriasis

Psoriasis is an autoimmune condition causing systemic inflammation that results in red patches of skin that may have silver scales and itching. According to Psoriasis.com, 1 out of 3 people with psoriasis will also experience joint symptoms, which is referred to as psoriatic arthritis.¹ It can also affect the nails resulting in abnormal nail growth and pitting. Skin cell growth is accelerated with this condition causing skin to pile up in patches rather than shed. It commonly occurs on the torso, elbows, scalp and knees. 

A study found a higher incidence of migraine in psoriasis patients (3.3%) than in the control group (2.9%).²

Raynaud’s Syndrome

Raynaud’s phenomenon is a vascular disorder that causes blood vessels in the fingers and toes to constrict. The affected areas can turn pale and blue due to lack of blood flow and can be painful when blood flow returns. The etiology of this condition is unknown and can be considered a primary disorder or it can occur due to another condition.

Studies have demonstrated a higher rate of Raynaud’s phenomenon in those with migraine compared to those without^1,2 and have found that women are more affected.

Red Ear Syndrome

Red Ear Syndrome is a rare phenomenon characterized by attacks of burning sensations and reddening of one or both ears. This condition has been primarily associated with migraine as well as trigeminal autonomic cephalalgias. Triggers are similar to trigeminal neuralgia and include but are not limited to chewing, temperature changes, gentle touch and/or hair bruising.

As of 2013, there were only 100 documented cases of Red Ear Syndrome and 81% (60/74) of patients reported in the literature with Primary Red Ear Syndrome had a personal history of migraine.¹

Temporomandibular disorders, upper cervical spine abnormalities (which are also comorbid with migraine) can cause red ear syndrome.¹ 

Restless Leg Syndrome

Restless leg syndrome (RLS) is a sensory neurological disorder where someone feels an uncomfortable sensation in their legs and experiences an uncontrollable urge to move them. It commonly occurs while at rest, before and/or during sleep and may become worse over time. Unfortunately, moving the legs only provides relief for a short time.

“Previously reported prevalence rates of RLS in migraine patients have ranged from 8.7 % to 39.0 %, with no significant differences between migraineurs with aura (MAs) and migraineurs without aura (MOs)"¹

Both restless leg syndrome and migraine are more common in women. A genetic study found an association between the Meis Homeobox 1 gene and increased risk of restless leg syndrome in those who have migraine, specifically migraine with aura.¹

Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is an autoimmune condition that causes inflammation in the lining of the joints. It most commonly affects the hands, wrists and knees but the inflammation can also become systemic, affecting other areas of the body such as the heart, lungs and kidneys. Some common symptoms are pain, swelling, and stiffness in the joints when waking up in the morning or after periods of inactivity. Migraine and rheumatoid arthritis appear to have a bidirectional relationship, meaning someone with migraine is more likely to develop rheumatoid arthritis and vice versa. 

A study found the incidence of RA in the migraine group was higher than the control group (2.0% vs. 1.4%) and incidence of migraine was higher in the RA group than controls (6.4% vs 4.6%).¹ 

Rosacea

Rosacea is a skin condition characterized by red, rosy areas on the face. Blood vessels, bumps and pimples may also be visible. In some cases, it can appear on the chest, scalp and neck.

In a study, those with rosacea were 1.96 times more likely to have migraine than in a non-rosacea population.¹ 

Sinusitis

Sinusitis is an inflammation of the tissue lining the sinuses. Acute sinusitis is often caused by common cold or allergies and may lead to a bacterial sinus infection. Sinusitis most commonly lasts 2-4 weeks. Chronic sinusitis can occur from a polyp or infection and lasts three months or longer.

A study found that greater than 80% of patients presenting with sinusitis met the criteria for migraine disease.¹

It is hypothesized that the activation of the trigeminal-autonomic reflex causes sinus-like symptoms: mid-facial pain, stuffy nose, nasal drainage and loss of smell. It is unclear whether or not sinusitis and migraine are truly comorbidities or migraine is manifesting with symptoms that are typically associated with sinusitis.

Sjögren’s Syndrome

Sjögren’s Syndrome is an autoimmune condition that targets the moisture-producing glands. Two hallmark symptoms of this condition are dry eyes and mouth but it can impact almost every body system. This condition can be a primary disorder or can occur due to another condition. Like migraine, it affects more women than men.

A study found that 46% of patients with primary Sjögren’s syndrome were also diagnosed with migraine.¹

Spinal Cord Injury

Spinal cord injuries (SCI) vary in severity and occur usually due to falls, accidents or trauma. A complete spinal cord injury occurs when the spinal cord is severed and the brain is unable to communicate to the area below the injury resulting in paralysis and lack of sensation. With an incomplete spinal cord injury, the person still has some movement and sensation to the area below the injury.

A study looking into the relationship between spinal cord injuries and migraine found the prevalence of migraine was higher in the population with SCI (28.9%) than in those without SCI (9.9%).¹

Spontaneous Coronary Artery Dissection (SCAD)

Spontaneous coronary artery dissection (SCAD) is an emergency cardiovascular condition where the inner layer of one or more coronary artery tears and causes a blockage resulting in decreased blood flow to the heart. Consequently, a person can experience a heart attack, changes in heart rhythm and/or cardiac arrest.

In a recent study of 585 SCAD patients, 40% also had migraine.¹

The study found that subjects with SCAD and migraine were more likely to be female, younger at the time of dissection and had a history of depression.¹

Suicide

Suicide is the act of intentionally harming oneself to cause death. Suicidal ideations are contemplations or thoughts about suicide.

“The rates of suicidal ideation and suicide attempts were the highest for chronic migraine with aura (ideation: 47.2%; attempts: 13.9%) and lowest in migraine-free controls (ideation: 2.8%; attempts: 0%). Migraine with aura and depression were associated with higher risks of suicidal ideation and suicide attempts.”¹

Anxiety, mood disorders and PTSD are comorbid conditions with both migraine and suicide. 

SUNCT/SUNA

Two types of trigeminal autonomic cephalgias (TACs) are SUNCT and SUNA. SUNCT is also known as short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. SUNCT is characterized by short bursts of severe stabbing or burning pain around one eye, frequently accompanied by redness and tearing from the eye. SUNA stands for short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms. The symptoms are similar to those of SUNCT. Someone with SUNA may have either redness or tearing, or may have neither symptom.

A study of 102 subjects with either SUNCT (65) or SUNA (37) found “more than half of each group had a personal or family history of migraine that resulted in more likely photophobia, phonophobia and persistent pain between attacks.”¹

Superior Oblique Myokymia

Superior oblique myokymia is a condition that causes rapid eye twitching. The superior oblique is a muscle that helps control the eye movements. Myokymia means involuntary muscle movement. The muscle surrounding the eye begins contracting leading to symptoms such as double vision or seeing a still object move up and down.

A small study of 37 subjects with superior oblique myokymia found that 100% of subjects had a history of migraine symptoms and auras.¹ Another study of 44 subjects with superior oblique myokymia also reported that 100% of subjects had a history of migraine and visual auras.² 

Systemic Lupus Erythematosus

Systemic Lupus Erythematosus also known as lupus is a systemic autoimmune disease that causes widespread inflammation in the body. The organ systems commonly affected are the kidneys, skin, nervous system and lungs but lupus can also affect the joints. Headaches are a common symptom among those with lupus and migraine is extremely prevalent as well.

A study of 168 patients with lupus found that 39% had headaches that met diagnostic criteria for migraine while 23% met the criteria for other headache types.¹

Takotsubo Cardiomyopathy

Takotsubo Cardiomyopathy also known as apical ballooning syndrome, or “broken heart syndrome” is a reversible dysfunction of the left ventricle (the heart’s main pumping chamber). The bottom part of the left ventricle balloons outward which leads to reduced pumping or contraction of the heart. The most common symptoms are chest pain and shortness of breath and can lead to severe complications such as cardiogenic shock.

A small study found that out of 25 patients with Takotsubo Cardiomyopathy 11 people (44%) had a migraine history versus 6 people (12%) in the control group.¹  

Temporomandibular Disorders

Temporomandibular Disorders are disorders of the jaw joints which can be related to the muscles that control the jaw, the joint itself or the hinge point. TMD and migraine are both more common in women from young adulthood to midlife and can lead to an increased risk of disability.

A study found those with TMD were 1.8-2 times more likely to have other primary headaches (such as migraine and tension headache) in comparison to controls.¹

Traumatic Brain Injury/ Post-Traumatic Headache

Traumatic brain injury occurs after an injury to the head. Classifications of TBI can be mild (like a mild concussion), moderate or severe. Symptoms will vary based on severity but can include: disorientation, amnesia, decreased level of consciousness, balance issues, impulsivity, changes in emotions, headache, difficulty with concentration, etc.

Post-traumatic headache occurs within seven days after a traumatic brain injury. Those impacted with post-traumatic headache frequently have migraine-type symptoms, tension-type symptoms or symptoms of other primary headache disorders. In one study of people with migraine disease and post-traumatic headache, those who had migraine prior to injury had a two times increase in the frequency and intensity of headaches after the injury.¹

Hong et. al found that "up to 49% of post-traumatic headache met the criteria for migraine, followed by tension-type headache (up to 40%).”²

Trigeminal Neuralgia

The trigeminal nerve is the largest of the 12 cranial nerves and is made up of three branches. It relays sensations from the face, oral cavity and mucous membranes to the brain. Trigeminal Neuralgia (TN) is a neurological condition affecting the trigeminal nerve which causes a severe burning or shock-like pain in the face or mouth for a period of seconds to minutes. The pain typically presents on one side and without warning. It is thought that the condition most often occurs due to nerve injury, damage to the myelin sheath that surrounds nerves and/or compression by a tumor or blood vessel next to the nerve. TN pain can be triggered by common activities like chewing, talking, gentle touch and/or pressure to the face.

"Among migraine subtypes, patients with migraine with aura were at greater risk of trigeminal neuralgia development.”¹ 

Visual Snow

Visual snow is a neurological disorder that affects the way the brain processes images and causes abnormal vision changes. It is important to note, no structural abnormalities exist within the eyes. Images may constantly appear with floaters, flashing lights and/or static and these symptoms remain with closed eyes. Other symptoms that may co-occur are photophobia, tinnitus, palinopsia, nyctalopia and more.

"Of 120 patients with "visual snow," 70 patients also had migraine and 37 had typical migraine aura."¹

Vulvodynia

Vulvodynia is a condition where chronic pain occurs in the vulva, located on the external female genitalia, for greater than three months. The pain occurs without a known cause and is often described as a burning or itching sensation.

One study found that 30% of those with vulvodynia also had migraine.¹

In addition, vulvodynia shares many comorbidities with migraine such as chronic pain, fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome.