Target Health Blog

Migraine

October 1, 2018

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Congratulations to our friends and colleagues at Eli Lilly and Co on the U.S. FDA approval of its migraine drug Emgality (galcanezumab), a CGRP-inhibitor. Lilly said it will offer the drug at no cost for a year to millions of patients with commercial insurance, a move that reflects increased scrutiny of high prescription costs in the U.S. and fierce competition in a hot treatment area.

The Head Ache, George Cruikshank (1819)
Graphic credit: George Cruikshank -
http://metmuseum.org/art/collection/search/393320, Public Domain, https://commons.wikimedia.org/w/index.php?curid=251827

A migraine is a primary headache disorder characterized by recurrent headaches that are moderate to severe. Typically, the headaches affect one half of the 1) ___, are pulsating in nature, and last from two to 72 hours. Associated symptoms may include nausea, vomiting, and sensitivity to light, sound, or smell. The pain is generally made worse by physical activity. Up to one-third of people have an aura: typically a short period of visual disturbance that signals that the headache will soon occur. Occasionally, an aura can occur with little or no 2) ___following it. The underlying causes of migraines are unknown.

Migraines are believed to be due to a mixture of environmental and 3) ___ factors. About two-thirds of cases run in families. Changing hormone levels may also play a role, as migraines affect slightly more boys than girls before puberty and two to three times more women than men. The risk of migraines usually decreases during pregnancy. The underlying mechanisms are not fully known. They are, however, believed to involve the nerves and blood vessels of the brain. Migraines are believed to be a neurovascular disorder with evidence supporting a mechanism starting within the brain and then spreading to the blood 4) ___. Some researchers believe neuronal mechanisms play a greater role, while others believe blood vessels play the key role. Others believe both are likely important. One theory is related to increased excitability of the cerebral cortex and abnormal control of pain neurons in the trigeminal nucleus of the brainstem. Low levels of the neurotransmitter serotonin, also known as 5-hydroxytryptamine, are believed to be involved.

Cortical spreading depression, or spreading depression, is a burst of neuronal activity followed by a period of inactivity, which is seen in those with migraines with an aura. There are a number of explanations for its occurrence including activation of NMDA receptors leading to calcium entering the cell. After the burst of activity the blood flow to the cerebral cortex in the area affected is decreased for two to six hours. It is believed that when depolarization travels down the underside of the brain, nerves that sense pain in the head and neck are triggered. The exact mechanism of the head pain which occurs during a 5) ___ is unknown.

Migraines typically present with self-limited, recurrent severe headache associated with autonomic symptoms. About 15-30% of people with migraines experience migraines with an aura and those who have migraines with aura also frequently have migraines without 6) ___. The severity of the pain, duration of the headache, and frequency of attacks are variable. A migraine lasting longer than 72 hours is termed status migrainosus. There are four possible phases to a migraine, although not all the phases are necessarily experienced:

The prodrome, which occurs hours or days before the headache

The aura, which immediately precedes the headache

The pain phase, also known as headache phase

The postdrome, the effects experienced following the end of a migraine attack

Prodromal or premonitory symptoms occur in about 60% of those with migraines, with an onset that can range from two hours to two days before the start of pain or the aura. These symptoms may include a wide variety of phenomena, including altered mood, irritability, depression or euphoria, fatigue, craving for certain food(s), stiff 7) ___ (especially in the neck), constipation or diarrhea, and sensitivity to smells or noise. This may occur in those with either migraine with aura or migraine without aura. The Aura phase of a migraine may consist of enhancements reminiscent of a zigzag fort structure, e.g. Negative scotoma, loss of awareness of local structures or Positive scotoma, local perception of additional structures and mostly one-sided loss of perception. The scintillations are of a zigzag pattern starting in the center of vision, surrounded by a somewhat larger area with distortion of shapes. The aura is a transient focal neurological phenomenon that occurs before or during the headache. Auras appear gradually over a number of minutes and generally last less than 60 minutes. Symptoms can be visual, sensory or motor in nature and many people experience more than one. Visual effects occur most frequently; they occur in up to 99% of cases and in more than 50% of cases are not accompanied by sensory or motor effects.

Vision disturbances often consist of a scintillating scotoma (an area of partial alteration in the field of vision which flickers and may interfere with a person's ability to read or drive). These typically start near the center of vision and then spread out to the sides with zigzagging lines which have been described as looking like fortifications or walls of a castle. Usually the lines are in black and white but some people also see colored lines. Some people lose part of their field of vision known as hemianopsia while others experience blurring.

Sensory aurae are the second most common type; they occur in 30-40% of people with auras. Often a feeling of pins-and-needles begins on one side in the hand and arm and spreads to the nose-mouth area on the same side. Numbness usually occurs after the tingling has passed with a loss of position sense. Other symptoms of the aura phase can include speech or language disturbances, world spinning, and less commonly motor problems. Motor symptoms indicate that this is a hemiplegic migraine, and weakness often lasts longer than one hour unlike other auras. Auditory hallucinations or delusions have also been described.

Anomalous experiences, such as so-called benign hallucinations, may occur in a person in a state of good mental and physical health, even in the apparent absence of a transient trigger factor such as fatigue, intoxication or sensory deprivation. The evidence for this statement has been accumulating for more than a century. Studies of benign hallucinatory experiences go back to 1886 and the early work of the Society for Psychical Research, which suggested approximately 10% of the population had experienced at least one hallucinatory episode in the course of their life. More recent studies have validated these findings; the precise incidence found varies with the nature of the episode and the criteria of "hallucination" adopted, but the basic finding is now well-supported.

Classically the headache is unilateral, throbbing, and moderate to severe in intensity. It usually comes on gradually and is aggravated by physical activity. In more than 40% of cases, however, the pain may be bilateral and neck pain is commonly associated with it. Bilateral pain is particularly common in those who have migraines without an aura. Less commonly pain may occur primarily in the back or top of the 8) ___. The pain usually lasts 4 to 72 hours in adults, however in young children frequently lasts less than 1 hour. The frequency of attacks is variable, from a few in a lifetime to several a week, with the average being about one a month. The pain is frequently accompanied by nausea, vomiting, sensitivity to light, sensitivity to sound, sensitivity to smells, fatigue and irritability. In a basilar migraine, a migraine with neurological symptoms related to the brain stem or with neurological symptoms on both sides of the body, common effects include a sense of the world spinning, light-headedness, and confusion. Nausea occurs in almost 90% of people, and vomiting occurs in about one-third. Many thus seek a dark and quiet room. Other symptoms may include blurred vision, nasal stuffiness, diarrhea, frequent urination, pallor, or sweating. Swelling or tenderness of the scalp may occur as can neck stiffness. Associated symptoms are less common in the elderly.

The Framingham Heart Study, did not find a link between late-life onset scintillating scotoma and stroke.

Initial recommended treatment is with simple 9) ___ medication such as ibuprofen and paracetamol (acetaminophen) for the headache, medication for the nausea, and the avoidance of triggers. Specific medications such as triptans or ergotamines may be used by those for whom simple pain medications are not effective. Caffeine may be added to the above. A number of medications are useful to prevent attacks including metoprolol, valproate, and topiramate. Approximately 15% of people, 10) ___-wide, are affected by migraines. It most often starts at puberty and is worst during middle age. In some women they become less common following menopause. As of 2016 it is one of the most common causes of disability.

Sources: nih.gov; Migraine by Oliver Sacks; Wikipedia

Graphic credit: Fair use: to illustrate an article discussing the book in question on the English-language Wikipedia, hosted on servers in the United States by the non-profit Wikimedia Foundation, qualifies as fair use under the Copyright law of the United States

As with Sacks' other writings, the book is a comprehensive review of the subject aimed at the lay population and uses numerous case histories. Sacks describes the nature of and treatments for migraine in general and several various subtypes, particularly examining the visual aura feature that is common to many sufferers, along with the premonitorys. The particular focus of the book, however, is on the neuropsychological aspects of migraine.

ANSWERS: 1) head; 2) headache; 3) genetic; 4) vessels; 5) migraine; 6) aura; 7) muscles; 8) head; 9) pain; 10) world

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