Epilepsy & Migraine More than just a headache Epilepsy and migraine: are the two connected?

And how can migraines be managed to ease their sometimes crippling day-to-day impact? CCoovveerr SSttoorryy If you ve ever had a migraine, you ll know how much the pain and heightened sensitivity to light and sound affects your ability to function. The similarities between epilepsy and migraines and the fact they can occur together in individuals is prompting research into common causes and therapies. Here, we explore the kinship of these two conditions, the discoveries made so far, and consider ways to manage migraines and reduce the level of disruption they cause in daily life. Migraine or headache? Everyone has experienced a headache at some time in their lives, for a variety of reasons and to varying degrees. Generally headaches can be effectively treated with over-the-counter medication, however some people will experience a more severe and debilitating form of headache called migraine. The International Headache Society, an organisation made up of medical and allied health professionals as well as researchers, has published an internationally accepted classification of headaches. They define a headache as a migraine when: 1. The pain can be classified by at least two of the following: one sided moderate to severe throbbing aggravated by movement 2. It occurs with a least one of these symptoms: nausea vomiting photophobia (sensitivity to light) phonophobia (sensitivity to noise) 3. The headache lasts between 4 and 72 hours. Other symptoms can include: osmophobia (sensitivity to smell) aura (visual disturbances such as bright zigzag lines, flashing lights, difficulty focusing or blind spots lasting 20-45 minutes) difficulty concentrating, confusion a general feeling of being extremely unwell problems with articulation or co-ordination diarrhoea stiff neck and shoulders tingling, pins and needles, numbness or even one-sided limb weakness

speech disturbance paralysis or loss of consciousness (rare) Migraines may recur over years or decades at greatly varying frequency in the same individual, from a few a year to several a week. Migraine stages Like epilepsy, migraines occur in the following distinct phases : 1. Early warning symptoms (prodrome): Up to 24 hours beforehand, people may experience: mood changes, from elation to irritability nausea, appetite changes (intense hunger or lack of appetite), constipation, diarrhoea neurological changes, drowsiness, yawning, difficulty finding words (dysphasia), dislike of light and sound behaviour changes from being obsessional and hyperactive to lethargic aches and pains fluid balance changes, thirst, passing more fluid, fluid retention 2. Aura: Accompanies migraine attacks in about 20-30% of people. It temporarily affects the visual field of both eyes and lasts 5-60 minutes. Less commonly, aura affects sensation or speech. Several aura symptoms may follow in succession. 3. Headache (the attack or ictus ): People having a classical migraine (migraine with aura) may wait up to an hour from when the aura ends to when head pain starts, and may feel spaced out in between. Headaches are similar with common migraine (migraine without aura). The associated symptoms of nausea and vomiting can be more distressing than the headache. 4. Resolution and recovery (postdrome): Attacks end very differently. Sleep can restore some, or being sick. Others find effective medication improves attacks. For a few, nothing has worked so far but the headache taking its course. Afterwards people can feel drained for about 24 hours, or they can feel energetic even euphoric. Similarities between migraine and epilepsy Seizures are thought to result from an excessive reaction to stimuli, migraines from a type of chronic pain syndrome fundamentally neurovascular in nature that is, relating to nerves supplying veins and arteries transporting blood to the brain. Hence migraine and epilepsy have traditionally been considered separate disorders although a variety of antiepileptic drugs are now frequently used to treat migraine. Epilepsy and migraine do share defining

attributes . They are both episodic disorders. In other words, people affected are symptom-free in between recurrent attacks that are temporary and begin suddenly, and afterwards they fully recover. One epilepsy syndrome in particular shares characteristics of migraine. Benign epilepsy of childhood with occipital paroxysms causes partial seizures sometimes preceded by visual symptoms and followed in 25% to 40% of people by migraine-like headaches . In neurological disorders such as mitochondrial encephalomyopathies changes in cells resulting in muscle and nerve dysfunction patients present with both seizures and migraine. The similarities mean epilepsy and migraines can sometimes be mistaken for one another. Some types of migraine can begin with loss of consciousness and other symptoms, followed by a headache. Meanwhile seizures that occur in the lobe of the brain related to vision, the occipital lobe, can be confused with migraine visual auras. Although there are differences that clinicians should be able to determine, such as shimmering or zigzag uncoloured lines for migraine auras, and coloured visual hallucinations for epilepsy. Further, migraines and epilepsy often exist together. Migraine is common in people with epilepsy, whereas epilepsy is rare in migraineurs. Between 9-10% of the general population suffer migraines compared to the population of people with epilepsy, up to 20% of whom reportedly experience migraine . Another hospital-based study published this year reports that 25.6% of participants with epilepsy had migraines compared to 15.2% of the control group who did not have epilepsy . Although headache often develops after an epileptic seizure, it is extremely rare for a migraine attack to trigger a seizure a phenomenon called migralepsy . In 2004, this was defined in the International Classification of Headache Disorders II as a migraine with aura, with a seizure that either occurs during or within one hour of the migraine . This concurrence of epilepsy and migraine in some people suggests (among other possibilities ) that the two may share a pathophysiological or genetic basis. Common pathophysiologic pathways there a biological link? is

Recent discoveries into the basis of migraine have resulted in a meeting of the theories of epilepsy

and migraine pathophysiology the changes in function associated with a disease or syndrome Epilepsy360. -December 2009

and the possibility one day of new common treatment approaches. It is well recognised that whole families can share a tendency to suffer migraine headaches. The risk of migraine is up to 50% greater in relatives of people with migraine than among relatives of people without migraine . Recently research into migraine has revealed genetic abnormalities related to dysfunction in the ion channels valves that let ions such as potassium, sodium and calcium in and out of the cell. This dysfunction could alter the brain s response threshold to internal and external triggers, causing auras and pain. Meanwhile, some epilepsy disorders have also been traced to ion channel dysfunction and dubbed channelopathies. In the future a clarification of the role of ion channel dysfunction in migraine and epilepsy may lead to this being a new target for effective prophylactic (preventive) drugs for both conditions, says Dr Alessandro Zagami, Senior Staff Specialist at the Prince of Wales Hospital s Institute of Neurological Sciences. Says Zagami, Migraine is now considered a primary disorder of the central nervous system just as epilepsy is Central dysfunction may lead to a momentary excitation of the brain cells followed by a prolonged spreading of a depression-like inhibition of the brain cells resulting in the aura of migraine in predisposed patients. It may also result in dysfunction of brainstem and other nuclei that normally modulate sensory, particularly painful input from the cranial blood vessel walls, as well as influencing the response of the cranial blood vessels and blood flow. Such activation in the brainstem has been documented during migraine headache in humans. In the case of rare patients with familial hemiplegic migraine where paralysis occurs with migraine attacks, scientists have identified mutations in genes encoding for components of sodium, potassium or calcium ion channels, says Zagami. Some of these mutations also cause epilepsy in the same patients. It has even been suggested that some headaches could be epileptic seizures and in some people, these might be the only sign of epilepsy. This could result from the interplay between the source of the epileptic activity and its spread, which in

turn may activate a common pathway for head pain that is, the trigeminovascular system which consists of the trigeminal nerve and local cranial blood vessels. Impact on daily life Depending on severity, migraine can impact life greatly, as can epilepsy. When the two occur together the effects are compounded. This particularly burdens children at a time when they are growing and developing their academic and social skills. Migraine pain can be excruciating and can incapacitate sufferers for hours, even days. Prevalence peaks during the prime work and child rearing ages of 25 to 55 . Many (53%) say their headaches hinder activities or force bed rest, while 31% report missing work or school in a given three-month period. Most people (52% to 73%) report that migraine adversely affects their work and family relationships. Further, it overloads the healthcare system a recent US study estimated an $11.07 billion annual cost of medical care, including prescription drugs, for insured Americans. A better way Epilepsy and migraines can be very challenging on their own. But people with epilepsy who suffer migraines experience the combined impacts of the two. In this instance, migraine management is particularly important. Crucial steps include finding out more about migraine and its relationship to your epilepsy, plus lifestyle changes and seeing a doctor to prescribe effective medication for during and between migraine attacks. As researchers continue exploring the potential links between migraine and epilepsy, there is hope of treatment breakthroughs that will in future improve quality of life for people affected by either condition. References i Epilepsy and migraine M.E. Bigal et al, Epilepsy & Behavior 4 2003 ii Common Pathophysiologic Mechanisms in Migraine and Epilepsy M. A. Rogawski; Arch Neurol 2009

iii Migralepsy: A call for a revision of the definition G. Sances et al; Epilepsia 2009 iv Epilepsy and migraine M.E. Bigal et al, Epilepsy & Behavior 4 2003 v Migralepsy: A call for a revision of the definition G. Sances et al; Epilepsia 2009 vi Lipton RB, Silberstein SD. Why study the comorbidity of migraine? Neurology 1994;44:4 5. vii Headache Australia, www.headacheaustralia.org.au prescribed for more severe migraine. Many are fungus that grows on rye. They interact with Treatments and strategies based on serotonin, which is a hormone that acts receptors for the brain chemical serotonin, which Treatment and self-management strategies can both as a chemical messenger transmitting regulates pain awareness and blood vessel tone. help to prevent and ease the impact of migraine. signals between nerve cells and causes blood These drugs reduce inflammation and cause the Treatment is not just about taking a tablet but vessels to narrow. Sometimes stronger blood vessels to constrict, which helps relieve involves a person developing an individual non-steroidal anti-inflammatory drugs are the throbbing nature of the pain of migraine. migraine management plan consisting of required. Anti-emetic medications are important to lifestyle modifications, medication and The latest medications target specific areas now reduce the nausea common with migraine. The complementary therapies. believed to cause the pain. Although the exact

presence of nausea means the patient has mechanism for pain generation is still not impaired absorption of oral medications leading Medication known, the trigeminovascular system is

to reduced effectiveness. Sometimes over-the-counter medications relieve believed to be crucial, says the Prince of Wales

migraines. But many people find they can t. If Hospital s Dr Zagami. Preventive treatment you re one and your headaches change, or you

Activation of this system leads to Preventive medication is taken daily, whether or don t know the cause or nature of your headache excitation in the brainstem that in turn relays not a headache is present, to reduce the number consult your doctor. Even if your doctor pain signals to the relay system of the brain and severity of headaches. These include previously prescribed unsuccessful treatments, called the thalamus as well as the cortex. It also medications that block the beta-receptors, which it s worth another visit. Migraines can be causes peripheral release of sensory neuropep affect the blood vessels and levels of adrenaline managed but effective management relies on you tides which are chemicals that act as messengers in the nervous system; or antiepileptic drugs and your doctor working as partners.

between the nerve cells, especially calcitonin including valproic acid, topiramate and gene-related peptide, or CGRP. gabapentin that are known to reduce migraine

Acute treatment Hence, he says, the most effective acute

intensity. Calcium-channel blockers constrict This is treatment given preferably at the onset of anti-migraine drugs at present are the triptan blood vessels while some antidepressants impact a headache. Infrequent, less severe migraine may drugs because one of their effects is to block the headache independently of their antidepressant respond to over-the-counter medications such as release of CGRP. action. paracetamol, aspirin (which is not recommended Other acute therapies include non-steroidal While effective, these all have side-effects and for young children), and non-steroidal anti-inflammatory drugs and ergot preparations. need to be prescribed by a medical practitioner. anti-inflammatory drugs. Ergot drugs were originally derived from a Migraine-specific medications may be Epilepsy360. -December 2009

Headache types Location and symptoms Precipitating factors Treatment/prevention Allergy Generalised; often occurs with runny nose and sore eyes. Seasonal; allergens such as pollens trigger hay fever and sinusitis. May include anti-histamine medication and decongestant nasal sprays. Cluster Headache Episodic or chronic; severe pain centred around one eye. May cause drooping eyelid, watering eye and nasal congestion. Most common in males. None known. Treatment of acute attacks may include oxygen inhalation and medications that constrict the blood vessels and reduce transmission of pain signals. Preventive medications may include calcium channel blockers and corticosteroids. Hangover Migraine-like symptoms of throbbing pain and nausea, not localised to one side. Alcohol, the breakdown products of which dilate and irritate blood vessels of the brain and surrounding tissue. Treat with liquids like broth. Consume fructose (e.g. honey, tomato juice) to help burn alcohol. Drink alcohol in moderation. Ice-cream Headache Sharp pain in the front of the the middle of forehead or head in one temple straight after swallowing ice cream or an ice cold drink. Can cause pain behind the ear. Pain in the palate or throat from swallowing very cold food or liquids may refer pain to the head through the trigeminal nerve endings or the glossopharyngeal nerve. Migraine sufferers are prone to ice-cream headache. Avoid ice-cream or icy drinks. Tension-Type Headache A dull, non-throbbing pain, often bilateral, with tightness of scalp or neck. Severity remains constant. Emotional stress, hidden depression. Avoid stress. Use biofeedback, relaxation techniques, psycho-therapy, and treatment with tricyclic anti-depressant medication. Treat with rest,

aspirin, ibuprofen, naproxen sodium, ice packs, and muscle relaxants. Migraine Severe, one-sided throbbing pain, often with nausea, vomiting, cold hands, sensitivity to sound, light and smells. May occur with aura i.e. visual disturbances, numbness in arm or leg. Can last up to four days. Begins in children and may last beyond the 60s. Many triggers, including dehydration, certain foods, insufficient food, hormones, environmental such as sudden changes in weather, oversleeping or too little sleep, physical factors such eye, dental problems, over-exertion or strenuous exercise, certain medications. Eating can help, especially starchy foods; chemist or prescription medications; bed rest; and complementary therapies including massage, aromatherapy, yoga, physiotherapy, acupuncture and Alexander technique. Definitions of headache types, migraine stages, triggers, symptoms and treatment s adapted with permission from the Headache Australia website an excellent source of information about headache and migraine. viii Headache Australia,www.headacheaustralia.org.au xiii Common Pathophysiologic Mechanisms in Neurol 2009 ix Ictal headache and visual sensitivity M. Piccioli Migraine and Epilepsy M. A. Ro gawski; Arch xvii Migralepsy: A call for a revision of the et al; Cephalalgia 2008 Neurol 2009 definition G. Sances et al; Epilepsia 2009 x Migralepsy: Is the Current Definition Too xiv Common Pathophysiologic Mechanisms in xviii Epilepsy and Migraine Headache: Is There a Narrow? F. Maggioni et al; 2008 Migraine an d Epilepsy M. A. Rogawski; Arch Connec tion? S. Stevenson; J Pediatr Health Care; xi Common Pathophysiologic Mechanisms in Neurol 2009 2006 Migraine and Epilepsy M. A. Rogawski; Arch xv Migraine headaches: Diagnosis and xi x Migraine headaches: Diagnosis and Neurol 2009 management H. Abel; Optometry 2009 management H. Abel; Optometry; 2009 xii Ictal headache and visual sensitivity M. Piccioli xvi Common Pathophysiologic M echanisms in xx Migraine headaches: Diagnosis and et al; Cephalalgia 2008 Migraine and Epilepsy M. A. Rogawski; Arch management H. A bel; Optometry; 2009 Epilepsy360. -December 2009