What Is Migraine?

Migraine is a chronic neurologic disease characterized by persistent attacks of throbbing headache, typically on one side of the head, usually made worse by physical activity. It is associated with other bothersome symptoms such as nausea, vomiting, and extreme sensitivity to light (photophobia) or sound (phonophobia). Some patients also experience other symptoms, such as pain from stimuli that are not normally painful, for example from a light touch on the skin or a change in temperature, or they may experience tingling or numbness in the face or extremities

cause of Migraine

Theories explaining the cause of migraine have evolved over the past decades. The traditional vascular theory posited an initial phase of vasoconstriction in the cranial vasculature (aura phase) followed by compensatory intracranial or extracranial vasodilation activating the trigeminal sensory nerves surrounding the meningeal blood vessels, thus resulting in headache pain. Recent research has shown that migraine involves nerve pathways and brain chemicals. It has been proposed that GABAA receptors are involved in the pathophysiology of migraine. Cortical spreading depression (CSD) is a likely basis for migraine aura and the trigger for headache pain. However, uncertainties regarding mechanisms remain, including the exact origin of migraine pain, the mechanism underlying the paroxysmal nature, and features of migraine, and the exact site and mode of action of migraine-specific medications.

WHO Suffers from Migraine

Migraine is a common, debilitating medical condition. According to the US National Health Interview Survey, 15.9% of American adults aged 18 or over (21% of women and 10.7% of men) reported suffering at least one migraine or severe headache attack within the previous 3 months. Adults aged 18 to 44 years had the highest prevalence of migraine (18.7%) compared with other age groups.

Impact of Migraine

Migraine is a public health challenge with serious social and economic consequences. Migraine attacks are associated with an increased long-term risk of cardiovascular and cerebrovascular events such as myocardial infarction and stroke. Women suffering from migraine with aura may have an increased risk of cardiovascular death. There is a huge economic toll associated with this disorder. The pain of a migraine attack can persist for hours to days, and symptoms may disturb normal routine activities. At least half of individuals with migraine report severe impairment or need for bed rest. Acute migraine attacks are estimated to account for approximately 1.2 million visits to emergency departments in the United States every year. According to systematic analyses for the Global Burden of Disease Study, headache disorders were the second most frequent cause of disability after oral disorders in both men and women worldwide in 2017. Migraine accounted for the second greatest number of years lived with disability after low back pain in 2016. The Migraine Research Foundation estimates that healthcare and lost productivity costs associated with migraine are as high as $36 billion annually in the United States, and more than 157 million workdays are lost each year in the US because of migraine.

Medical Need

Many individuals with migraine are undiagnosed and therefore undertreated. Even when properly diagnosed, many patients with migraines do not achieve an adequate response to treatment, despite the wide variety of medications available for the treatment of migraine. In a survey of 8,233 respondents with episodic migraine, 56% of respondents reported an inadequate 2-hour pain-free response to their usual acute treatment, and 53.7% reported an inadequate response at 24 hours. Among the 44% of individuals who did achieve an adequate pain-free response at 2 hours, 25.7% reported that freedom from pain was not sustained at 24 hours. Migraine is refractory to treatment in approximately 5% of patients. In addition, patient acceptance and tolerability issues exist, and clinicians must consider potential side effects/adverse events (AEs), potential for loss of effect with time, drug dependence, patient-specific contraindications, and the potential for drug–drug interactions when choosing a medication for migraine.

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What is Epilepsy?

Epilepsy is a disease in which unusual electrical activity in the brain leads to seizures. An epileptic seizure results from abnormal activity in the brain causing loss of awareness or consciousness, or disturbances of movement, sensation (including vision, hearing, or taste), mood, or other cognitive functions. Characteristics of seizures differ, depending on whether the disturbance presents at a specific focus (focal epilepsy) or in both hemispheres (generalized epilepsy). Seizures can vary from the briefest lapses of attention or muscle jerks to severe and prolonged convulsions, and they can vary in frequency from fewer than 1 per year to multiple seizures per day.


There are various types of epilepsy, with many possible causes, including structural, genetic, infectious, metabolic, or immune factors, or there may also be a combination of contributing factors. For up to half of people with epilepsy, the cause is not known. On a continuous range from brief single seizures to refractory status epilepticus, seizure clusters represent an intermediate stage, with widely varying durations and numbers of discrete events and severities. Some individuals experience acute repetitive seizures (ARS), i.e., a bout or cluster of seizures over a short period of time in which mental status is relatively preserved between seizures. A common clinical definition of ARS is the occurrence of three or more seizures within 24 hours for patients whose habitual seizure frequency is fewer than three seizures per day. ARS is a serious medical condition that requires immediate treatment. Complications of ARS may include post-ictal psychosis; injury from falls and burns; and negative social and economic impact from frequent emergency room visits, hospitalizations, and missed school or workdays. In addition, an episode of ARS may progress to status epilepticus, which is an epilepsy emergency that may lead to permanent neurological injury and death. Another form of epilepsy is Lennox-Gastaut syndrome (LGS), a childhood-onset disorder that may evolve into severe developmental and epileptic encephalopathy. LGS has no single genetic cause, and in many cases a cause is not identified. LGS is traditionally defined by the following “triad” of features: (1) multiple seizure types that are often refractory to drugs (with tonic seizures being a hallmark feature), (2) a generalized slow spike and wave discharge pattern on EEG, and (3) cognitive and behavioral impairments.

Impact Of Epilepsy

Epilepsy is one of the most common neurological diseases and affects people of all ages, races, social classes, and geographical locations, affecting as many as 65 million people worldwide, with higher prevalence in low-income countries. The incidence and prevalence of epilepsy are slightly higher in men than in women. In the United States, approximately 3.4 million people have epilepsy (1.2% of the US population), including 3 million adults and 470,000 children.

Medical Need

Although epilepsy can be controlled with pharmacotherapy, significant unmet needs remain for many individuals with epilepsy. According to the US Centers for Disease Control, among individuals taking epilepsy medication, only 44% reported having their seizures adequately controlled. Overall, 20-30% of people with epilepsy remain refractory to treatment and are said to have drug-resistant epilepsy. In these individuals, seizures tend to recur despite intensive treatment.

People with uncontrolled seizures are often at high risk of experiencing adverse effects of treatment events because of a greater drug load and a higher number of prescribed drugs. Suboptimal or inappropriate use of antiepileptic drugs may also put the patient at risk of serious adverse events. Uncontrolled epilepsy is also associated with a substantially greater burden to patient quality of life as well as significant healthcare costs.

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