Migraine: Spectrum of Symptoms and Diagnosis

Home , Menstrual migraine, Retinal migraine, Thunderclap headache, Vascular headache

KEY POINT: MIGRAINE: SPECTRUM A Most patients develop migraine in the first 3 OF SYMPTOMS decades of life, some in the AND DIAGNOSIS fourth and even the fifth decade. William B. Young, Stephen D. Silberstein

ABSTRACT The migraine attack can be divided into four phases. Premonitory phenomena occur hours to days before headache onset and consist of psychological, neurological, or general symptoms. The migraine aura is comprised of focal neurological phenomena that precede or accompany an attack. Visual and sensory auras are the most common. The migraine headache is typically unilateral, throbbing, and aggravated by routine physical activity. Cutaneous allodynia develops during untreated migraine in 60% to 75% of cases. Migraine attacks can be accompanied by other associated symptoms, including nausea and vomiting, gastroparesis, diarrhea, photophobia, phonophobia, osmophobia, lightheadedness and vertigo, and constitutional, mood, and mental changes. Differential diagnoses include cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoenphalopathy (CADASIL), pseudomigraine with lymphocytic pleocytosis, ophthalmoplegic migraine, Tolosa-Hunt syndrome, mitochondrial disorders, encephalitis, ornithine transcarbamylase deficiency, and benign idiopathic thunderclap headache.

Migraine is a common episodic head- (Headache Classification Subcommittee, ache disorder with a 1-year prevalence 2004): of approximately 18% in women, 6% inmen,and4%inchildren.Attacks Recurrent attacks of headache, consist of various combinations of widely varied in intensity, fre- headache and neurological, gastrointes- quency, and duration. The attacks tinal, and autonomic symptoms. Most are commonly unilateral in onset; patients develop migraine in the first are usually associated with an- 67 3 decades of life, some in the fourth orexia and sometimes with nausea and even the fifth decade. The term and vomiting; some are preceded migraine is derived from the Greek by, or associated with, conspicu- word hemicrania, introduced by Galen ous sensory, motor, and mood dis- in approximately AD 200. turbances; and are often familial. In order to increase precision, the DIAGNOSIS International Headache Society (IHS) Early migraine descriptions stressed proposed and published its classifica- three features: the unilateral distribution of headache disorders in 1988 and tion of the headache, the presence of revised it in 2004 (Headache Classifi- a warning (often visual), and nausea or cation Subcommittee, 2004). The IHS vomiting. The Ad Hoc Committee on criteria added photophobia and pho- Classification of Headache described nophobia and required an untreated vascular headache of migraine type as duration of 4 to 72 hours.

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. " MIGRAINE: SYMPTOMS AND DIAGNOSIS

KEY POINTS: A Migraine headaches were formerly To establish a diagnosis of migraine At most, only divided into two varieties: classic and under the IHS classification, certain 30% of common, which are now called mi- clinical features must be present and migraineurs have classic graine with aura and migraine without organic disease must be excluded aura. The same aura. The aura is the complex of focal (Table 4-2). Several attacks, each patient may neurological symptoms that precedes lasting 4 to 72 hours (untreated), are have migraine or accompanies an attack. At most, necessary and must have two of the headache only 30% of migraineurs have ‘‘classic’’ following four pain characteristics: without aura, aura. The same patient may have unilateral location, pulsating qual- migraine migraine headache without aura, mi- ity, moderate to severe intensity, and headache with graine headache with aura, and mi- aggravation by routine physical activ- aura, and graine aura without headache. ity. In addition, the attacks must have migraine aura In addition to the symptoms de- at least one of the following associated without scribed in the IHS definition, other symptoms: nausea and/or vomiting, headache. symptoms of migraine are extremely and/or photophobia and phonopho- A If sufficient common. A wide variety of premoni- bia. Using these criteria, no single criteria but one tory symptoms may occur; nasal con- associated feature is mandatory for are present, the gestion and neck pain may be present; diagnosing migraine, although recur- headache is and the typical eye findings of cluster rent episodic attacks must be docu- called probable headache may occur with some regu- mented. Different patients or different migraine. larity (Table 4-1). attacks may fulfill entirely nonover- lapping criteria. If sufficient criteria but one are present, the headache is TABLE 4-1 Rates of Migraine called probable migraine. Table 4-2 Symptoms lists the current subtypes of migraine. A migraine attack usually lasts less Symptom Approximate % than a day; when it persists for more

* than 3 days, the term status migrain- Throbbing 80 osus is applied. Although migraine often Unilaterality* 61 begins in the morning, sometimes Moderate to 97 awakening the patient from sleep at severe* dawn, it can begin at any time of the Worse with 95 day or night. The frequency of attacks activity* is extremely variable, from a few in a lifetime to several in a week. The median Nausea* 87 68 attack frequency is 1.5 attacks per month; * Vomiting 56 10% of migraineurs have one or more Photophobia* 85 attacks per week (Stewart et al, 1994).

* The diagnosis of migraine with aura Phonophobia 80 requires at least two attacks with any Allodynia 65 two of three features: (1) one or more Nasal 70 fully reversible aura symptoms; (2) the congestion aura developing over more than 4 min- Neck pain 65 utes but lasting less than 60 minutes; and (3) the headache following the Stabbing pain 40 aura with a free interval of less than 60 Clusterlike eye 5 minutes. Migraine with aura is subdi- symptoms vided into migraine with typical aura *In International Headache Society criteria. (homonymous visual disturbance, unilateral numbness, or aphasia); migraine

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS: A Most migraineurs TABLE 4-2 International Classification of Headache Disorders. 2nd Edition, with migraine Migraine Classification with aura also have attacks 1. Migraine without aura. A 1.1 Migraine without aura In contrast to a transient 1.2 Migraine with aura ischemic attack, 1.2.1 Typical aura with migraine headache the aura of migraine evolves 1.2.2 Typical aura with nonmigraine headache gradually and 1.2.3 Typical aura without headache typically consists 1.2.4 Familial hemiplegic migraine of both positive (eg, scintillations, 1.2.5 Sporadic hemiplegic migraine tingling) and 1.2.6 Basilar-type migraine negative (eg, scotoma, 1.3 Childhood periodic syndromes that are commonly numbness) precursors of migraine features. 1.3.1 Cyclical vomiting 1.3.2 Abdominal migraine 1.3.3 Benign paroxysmal vertigo of childhood 1.4 Retinal migraine 1.5 Complications of migraine 1.5.1 Chronic migraine 1.5.2 Status migrainosus 1.5.3 Persistent aura without infarction 1.5.4 Migrainous infarction 1.5.5 Migraine-triggered seizures 1.6 Probable migraine 1.6.1 Probable migraine without aura 1.6.2 Probable migraine with aura 69 1.6.5 Probable chronic migraine

Data from Headache Classification Subcommittee. The International Classification of Headache Disorders. 2nd edition. Cephalalgia 2004;24(suppl 1):9–160.

aura with nonmigraine headache or the headache, but occasionally it occurs without headache; familial and spo- with the headache or only during the radic hemiplegic migraine; and basilar headache. In contrast to a transient migraine. Other varieties of migraine ischemic attack (TIA), the aura of mi- include retinal migraine and childhood graine evolves gradually and typically periodic syndromes. Most patients with consists of both positive (eg, scintilla- migraine with aura also have attacks tions, tingling) and negative (eg, sco- without aura. The aura usually lasts 20 toma, numbness) features. If the aura to 30 minutes and typically precedes is stereotypical, the diagnosis of migraine

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. " MIGRAINE: SYMPTOMS AND DIAGNOSIS

KEY POINTS: with aura is warranted, even if the the headache. If the headache is ab- A Almost any subsequent headache does not have sent, it is migraine aura without head- symptom or sign of brain typical migrainous features. Almost ache. Both may be associated with dysfunction any symptom or sign of brain dysfunc- premonitory symptoms. (Premonitory may be a tion may be a feature of the aura, but symptoms often extend into the head- feature of the commonly the aura is visual. ache or may begin in the headache migraine aura, Focal symptoms and signs of the phase). but commonly aura may persist beyond the headache the aura is phase. Formerly termed complicated Premonitory Phase visual. migraine, the IHS classification has Premonitory phenomena occur hours A Particularly in introduced two more-specific labels. to days before headache onset in about mid or late life, If the aura lasts for more than 1 hour 60% of migraineurs and can consist of the migraine but less than 1 week, the term migraine psychological, neurological, or general aura may not with prolonged aura was formerly (constitutional, autonomic) symptoms be followed by applied, but now the episode is called (Table 4-4). Psychological symptoms the headache migraine with aura and an atypical include depression, euphoria, irrita- (migraine feature. If the signs persist for more bility, restlessness, mental slowness, equivalent or than 2 weeks without radiographic hyperactivity, fatigue, and drowsiness. late-life evidence of infarction, it is called a Neurological phenomena include pho- migraine persistent aura without infarction. If a tophobia, phonophobia, and hyperos- accompaniment). neuroimaging procedure demonstrates mia, among others. General symptoms A Associated a stroke, a migrainous infarction has include a stiff neck, a cold feeling, symptoms of occurred. Particularly in mid or late life, sluggishness, increased thirst, increased migraine, such the aura may not be followed by the urination, anorexia, diarrhea, constipa- as nausea, headache (migraine equivalent or late- tion, fluid retention, and food cravings. photophobia, or life migraine accompaniment). Premonitory symptoms are present phonophobia, in approximately 60% of migraineurs may occur CLINICAL FEATURES before headache with equal frequency in migraine with OF MIGRAINE as part of the or without aura (Blau, 1980). Two premonitory The migraine attack can be divided into types of migraine premonitory phases phase. four phases: (1) premonitory, which are described: nonevolutive, which pre- occurs hours or days before the head- cede the attack by up to 48 hours, and ache; (2) the aura, which immediately evolutive, which start approximately precedes the headache; (3) the head- 6 hours before the attack, gradually ache itself; and (4) the postdrome increase in intensity, and culminate in 70 (Table 4-3). Migraine without aura the attack. A dopaminergic mecha- consists of at least the headache and nism has been suggested. More recent possibly the postdrome. Migraine with data suggest that many features of the aura consists of at least the aura and premonitory phase may develop during headache. Furthermore, associated symptoms of migraine, such as nausea, TABLE 4-3 Migraine Attack photophobia, or phonophobia, may occur before headache as part of the " premonitory phase (Giffin et al, 2003). Phase 1 Premonitory phase Although these findings belie the idea " Phase 2 Aura of a unique set of symptoms that apply " Phase 3 Headache specifically to the premonitory phase of headache, the concept of the pre- " Phase 4 Postdrome monitory phase with an identifiable set of symptoms before the pain of

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS: A In migraine, the TABLE 4-4 Premonitory Phenomena (Prodrome) headache may begin before or Psychological Neurological General simultaneously with the aura, Depressed Photophobia Stiff neck or the aura may Hyperactive Difficulty concentrating Food cravings occur in isolation. Rarely, auras Euphoric Phonophobia Cold feeling may occur Talkative Dysphasia Anorexia repeatedly. This may be many Irritable Hyperosmia Sluggish times an hour Drowsy Yawning Diarrhea or for as long as constipation Restless several months. Thirst These have been termed Urination migraine aura Fluid retention status, but other organic causes must be considered. migraine remains important. It indi- occur during this ‘‘gap.’’ The headache A Visual aura cates that (1) the pain is but one fea- may begin before or simultaneously is the most ture of a complex neurological process with the aura, or the aura may occur common of the and (2) symptomatic treatments may be in isolation. Rarely, auras may occur neurological possibleevenbeforepaindevelops. repeatedly. This may be many times an events in hour for as long as several months. migraine. It Aura These have been termed migraine aura occurs in up The migraine aura is composed of focal status, but other organic causes must to 99% of neurological phenomena that precede be considered (Silberstein and Young, patients who or accompany an attack. Most aura 1995). Sacks described two variations: have an aura symptoms develop over 5 to 20 min- scotomata occurring repeatedly, even and often has a hemianopic utes and usually last less than 60 alternating sides; and closely repeating distribution. minutes (Headache Classification Sub- cycles of migrating sensory auras occur- committee, 2004). The aura can be ring for hours on end (Sacks, 1985). characterized by visual, sensory, or Patients may experience more than motor phenomena and may also in- one type of aura, with a progression 71 volve language or brain stem distur- from one symptom to another. Most bances (Table 4-5). If it occurs, the patients with a sensory aura also have a headache usually begins within 60 visual aura (Figure 4-1) (Airy, 1871). minutes of the end of the aura. In Visual aura is the most common of one prospective study, headache fol- the neurological events; it occurs in lowed the aura only 80% of the time up to 99% of patients who have an aura (Jensen et al, 1986). If the headache is and often has a hemianopic distri- delayed, most patients fail to return to bution. The aura may consist of pho- a normal sense between the end of the topsia (the sensation of unformed aura and the onset of the headache. flashes of light before the eyes), sco- Fears, somatic complaints, alterations toma (partial loss of sight) (Lance and inmood,disturbancesofspeechor Anthony, 1966), or the most diagnos- thought, or detachment from the en- tic aura of migraine, the fortification vironment or from other people may spectrum (Airy, 1871). Auras vary in

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. " MIGRAINE: SYMPTOMS AND DIAGNOSIS

cated auras include teichopsia (Greek TABLE 4-5 Aura teichos, [town] wall, + opsis, vision) or fortification spectrum, the most char- " Visual acteristic visual aura of migraine. An arc of scintillating lights, usually but Scotoma; photopsia or not always beginning near the point of phosphenes, geometric forms, fortification spectra fixation, may form into a herringbone- like pattern that expands to encompass Objects may rotate, oscillate, an increasing portion of a visual hemi- or shimmer; brightness often appears very bright. field. It migrates across the visual field " with a scintillating edge of often zigzag, Visual Hallucinations or flashing, or occasionally colored phe- Distortions nomena. The visions of Hildegard of Metamorphopsia, macropsia, Bingen, an 11th century abbess, have zoom or mosaic vision been attributed in part to her migrainous " Sensory auras, as have the visions of prophets, Paresthesias, often including Ezekiel, who experienced migrating, often lasting for positive and negative visual phenom- minutes (cheiro-oral) ena, sparkling, boiling, or fermenting Can become bilateral lights, that march across the visual field. Visual distortions and hallucinations, " Olfactory speculated to represent Lewis Carroll’s Hallucinations descriptions in Alice in Wonderland, " Motor can occur. These phenomena are more Weakness or ataxia " Language Dysarthria or aphasia " Delusions and Disturbed Consciousness De´ja` vu, multiple conscious trancelike states

72 their complexity. Elementary visual disturbances include scotomata, simple flashes (phosphenes), specks, or geometric forms. They may move across the visual field, sometimes crossing the midline. Shimmering or undulations in the visual field may also occur and may be described by patients as ‘‘heat waves.’’ These ‘‘minor visual disorders’’ are more likely to occur during than before the headache (Selby and Lance, FIGURE 4-1 Migraine aura. It grows 1960) and often do not meet the full with the passage of time. criteria for migraine aura. Because they Airy H. On a distinct form of transient hemianopsia. Philos Trans R Soc Lond 1871;160:247–270. Re- are bilateral they are believed to arise printed with permission from the Royal Society. from the occipital cortex. More compli-

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINT: common in children, are usually fol- sense. Paresthesias begin bilaterally or A Periodic lowed by a headache, and are charac- become bilateral in half of patients. neurological terized by a complex disorder of visual Sensory auras rarely occur in isolation phenomena, perception that may include metamor- and usually follow a visual aura. Ol- which may be the phopsia, micropsia, macropsia, zoom, factory auras may also occur and may aura of migraine, or mosaic vision. Nonvisual symptoms be confused with epilepsy. can occur in can occur and include complex diffi- Motor symptoms may occur in more isolation without culties in the perception and use of the than 10% of patients, often in associa- the headache. body (apraxia and agnosia); speech tion with sensory symptoms; however, These phenomena and language disturbances; states of true weakness is rare and is always (scintillating double or multiple consciousness as- unilateral. Genetically proven familial scotoma, recurrent sociated with de´ja` vu or jamais vu; and hemiplegic migraine is characterized by sensory, motor, elaborate dreamy, nightmarish, trance- true weakness and is described below. and mental phenomena) must like, or delirious states. Olfactory hallu- Sensory ataxia is often reported as be differentiated cinations may also occur. weakness. Hyperkinetic movement dis- from transient Paresthesias characterize the second orders, including chorea, have been ischemic attacks most common aura and occur in about reported. Aphasic auras have been and focal seizures one third of migraineurs with aura reported in 17% to 20% of patients and are diagnosed (Case 4-1). They are typically cheiro- (Jensen et al, 1986). However, since as migraine only oral with numbness starting in the patients are rarely examined during after full hand, migrating up the arm, and then an aura, many of the reported cases investigation jumping to involve the face, lips, and may be dysarthria and not aphasia. and reasonable tongue. The leg is occasionally involved. follow-up. As with visual auras (with positive, fol- Migraine Aura lowed by negative, symptoms), pares- Without Headache thesias may be followed by numbness Periodic neurological phenomena, which and, in a few cases, loss of position may be the aura of migraine, can occur

Case 4-1 A 28-year-old, right-handed woman is being treated for episodic migraine without aura. She calls one morning because she notes difficulty seeing on the right side, noting ‘‘things are missing,’’ but with no scintillations or other positive visual phenomena. This spell is similar to several that she had 15 years before in childhood. After 1/2 hour she notes paresthesias in her right hand that migrate up her arm, also skipping to her right face, then 73 progressing to her right leg. On arrival at the office 1 hour later she has a severe, holoacranial headache and an expressive aphasia. Her visual and sensory symptoms have resolved. On examination there is no hemiplegia, hemisensory loss, or hemianopsia. The aphasia resolves within 5 minutes of arrival in the office, with a total duration of less than 1 hour. The severe headache resolves after intravenous prochlorperazine and ketorolac. Comment. The above case illustrates the spread of fairly typical visual aura (no positive visual phenomena and no clear evidence of spread within the visual domain) to the sensory and language cortex, consistent with spreading regional depression. If motor weakness had occurred, it would be typical of hemiplegic migraine. Each component resolved within 1 hour, which is typical of migraine aura, and, according to many experts, reflects a low risk of either secondary causes of migraine or evolving into a migraine stroke.

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. " MIGRAINE: SYMPTOMS AND DIAGNOSIS

KEY POINTS: in isolation without the headache. chronic neurological disorder at 5-year A Transient These phenomena (scintillating sco- follow-up, suggesting that these are neurological phenomena not toma, recurrent sensory, motor, and benign migrainous accompaniments. associated with mental phenomena) must be differ- Migraine-related visual symptoms headache can entiated from TIAs and focal seizures were investigated in the Framingham occur, often in and are diagnosed as migraine only study (Wijman et al, 1998). Visual symp- patients over the after full investigation and reason- toms that could be interpreted as age of 40 able follow-up. Transient visual distur- migraine related occurred in slightly (late-life bances with flickering or scintillating more than 1% of patients but met the migrainous phenomena also occur with numerous IHS definition of migraine in only 19% accompaniments other conditions, including blood cell of these cases. The episodes, which or transient diseases, retinal detachment, cluster often recurred (10 or more times), migrainous headaches, trauma, and syncope, but usually failed to develop slowly over accompaniments); are not generally associated with cere- 4minutes.Theywereoftennotac- 57% of patients had a history of brovascular embolic or thrombotic dis- companied by headache and often recurrent ease. Headache occurring in associa- occurred without a headache history. headache. tion with the symptoms of aura will Migraineurs have approximately 3 times A help confirm the diagnosis but does the risk of developing transient vi- Transient not include slightly less than half of sual disturbances than nonmigraine- migrainous the patients who had headache with urs. Gradual onset occurred in slightly accompaniments (scintillating aura and aura without headache at less than half of subjects. If headache scotomata, some time. follows transient visual disturbance, it numbness, Transient neurological phenomena is more likely migraine in persons with aphasia, not associated with headache can oc- a history of migraine headache. The dysarthria, and cur, often in patients over the age stroke rate among subjects with mi- motor weakness) of 40 (late-life migrainous accompani- grainous visual symptoms is less than that occur for ments or transient migrainous accom- in subjects with TIAs and similar to that the first time paniments); 57% of patients had a in subjects without TIAs or migrainous after the age history of recurrent headache (Fisher, phenomena. of 45 can be 1980). The attacks of episodic neuro- Transient migrainous accompani- easily confused logical dysfunction last from 1 minute to ments (scintillating scotomata, numb- with TIAs of 72 hours and have variable recurrence ness, aphasia, dysarthria, and motor cerebrovascular origin. Diagnosis rates (one attack, 27%; two to 10 at- weakness) that occur for the first time in all but the tacks, 45%; more than 10 attacks, 28%). after the age of 45 can be easily confused 74 most classical Isolated neurological spells attributed with TIAs of cerebrovascular origin. casesisstillby to migraine are a diagnosis of exclu- Diagnosis in all but the most classical exclusion. sion unless typical scintillating scotoma cases is still by exclusion (Table 4-6). A occurs. The headache Headache of migraine can Thirty-two percent of Cornell neu- occur at any rologists had a history of transient neu- A migraine headache is typically unilat- time of day or rological symptoms, most commonly eral, throbbing, moderate to marked in night but occurs visual (field cuts, obscurations, scoto- severity, and aggravated by routine most frequently mata) and less commonly nonvisual physical activity. The IHS does not on arising in the symptoms (hemiparesis, clumsiness, require all of these features: pain may morning. paresthesias, dysarthria) (Levy, 1988). be bilateral and throbbing or unilateral Migraine was reported in 29%, occur- and achy. The headache of migraine ring in 44% of those reporting and can occur at any time of day or night 22% of those not reporting transient but occurs most frequently on arising central nervous system dysfunction. in the morning (Selby and Lance, 1960). None developed any residual deficit or The onset is usually gradual; the pain

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS: Lance, 1960). During an attack, pain A Migraine TABLE 4-6 Migraine may move from one part of the head Equivalents headache is to another and may radiate down bilateral in 40% the neck into the shoulder. Physical and unilateral " Scintillating scotoma activity or simple head movement com- in 60% of cases; " Paresthesias monly aggravate the pain. Patients pre- it consistently " Aphasia fer to lie down in a dark, quiet room. occurs on the " Many migraineurs have headache same side in Dysarthria profiles that do not meet the IHS cri- 20% of patients. " Hemiplegia teria for migraine. Some are probable A The pain of " Blindness migraine, missing one criterion; others migraine will be shorter and less severe and headache varies " Blurring of vision often meet the IHS criteria for episodic greatly in " Hemianopia tension-type headache (TTH). Many intensity, " Transient monocular patients note that their headache be- ranging from blindness gins as a TTH and builds into a ‘‘mi- annoying to incapacitating, " Ophthalmoplegia graine.’’ The authors of this chapter although most " believe these phenomenological TTHs Oculosympathetic palsy are all migrainous in nature. They have migraineurs report at least " Mydriasis more migraine features than TTH moderate pain. " Confusion/stupor features and, unlike typical TTH occurring in nonmigraineurs, respond to spe- A Many " Cyclical vomiting cific migraine drugs (Lipton et al, 2000). migraineurs " Seizures Migraineurs may also experience short- have headache profiles that do " Diplopia lived jabs of pain, lasting for seconds, not meet the occurring between more characteris- " Deafness International tic migraine attacks (so-called idio- Headache " Recurrence of stroke deficit pathic stabbing headache). The pain Society criteria " Chorea is described as an ‘‘icepick,’’ ‘‘needle,’’ for migraine. ‘‘nail,’’ ‘‘jabs and jolts,’’ or ‘‘pinprick’’ A headache, and occurs in about 40% of Scalp tenderness and other forms migraineurs. of cutaneous peaks and then subsides and usually Scalp tenderness and other forms of allodynia lasts less than 24 hours, with a range cutaneous allodynia develop during develop during of 4 to 72 hours in adults and 2 to 48 untreated migraine in 60% to 75% of untreated 75 hours in children. The headache is cases. This tenderness may involve the migraine in bilateral in 40% and unilateral in 60% head and neck and prevent the patient 60% to 75% of cases; it consistently occurs on the from lying on the affected side. Allody- of cases. same side in 20% of patients (Selby nia typically begins in the trigeminal and Lance, 1960). Migraineurs whose distribution and spreads to involve the headaches alternate sides do not arms. Characteristically it develops ap- develop more consistently lateralized proximately 1 hour after the throbbing headache with the passage of time. headache. Typical symptoms of allody- The pain varies greatly in intensity, nia are listed in Table 4-7.Afterthe ranging from annoying to incapacitat- migraine headache ends, allodynia may ing, although most migraineurs report persist for several hours. at least moderate pain (Stewart et al, 1994). The pain has a throbbing qual- Associated Phenomena ity, particularly when it is severe, but it Migraine attacks are accompanied by can be tight or bandlike (Selby and other associated symptoms that often

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. " MIGRAINE: SYMPTOMS AND DIAGNOSIS

KEY POINTS: room. Others will have lightheaded- A Gastric emptying TABLE 4-7 Typical Questions ness and vertigo. Premonitory symp- can be delayed to Evaluate and oral drug toms, such as exhilaration, agitation, Allodynia in fatigue, lethargy, disorientation, hypo- absorption Migraineurs impaired during mania, anger, rage, or depression, can an attack of Do you experience pain or continue into the headache. Constitu- migraine, and unpleasant sensation on your skin tional, mood, and mental changes are vomiting may during migraine attack when you almost universal. Blurry vision, nasal result in drug engage in any of the following stuffiness, pallor or redness, and sensa- loss, thereby activities (Yes, No, N/A)? tions of heat, cold, or sweating may compromising Combing your hair occur. Fluid retention can develop the therapeutic Pulling your hair back hours to days before the headache. effectiveness Frank edema may precede, accompany, of orally (eg, ponytail) or follow the headache, with resolution administered Shaving your face drugs. A recent of the fluid retention after the head- Wearing eyeglasses study has ache resolves. demonstrated Wearing contact lenses The prevalence of associated symptoms is higher in clinic-based than that gastric Wearing earrings emptying may population-based studies, probably be- be delayed Wearing necklaces cause more effective interviewing tech- interictally Wearing tight clothes niques and more definitive criteria are compared Taking a shower (when shower used in the clinic. A selection bias to- with controls. water hits your face) ward patients with more severe head- A ache may result in more symptoms Neck pain is Resting your face on the pillow common in on the side of pain being reported. Studies that graded the patients with severity of nausea, photophobia, and migraine, Heat exposure (eg, cooking, phonophobia improved the differentia- placing heating pads on your occurring in face) tion of migraine from TTH; by defini- 60% to 90% tion, these symptoms were more preva- of migraines Cold exposure (eg, breathing lent and more severe in migraineurs. studied: 20% in through your nose on a cold day, placing ice packs on your Theprevalenceofmigraine-associated the premonitory symptoms, particularly nausea and vom- phase, 60% face) iting, has also been estimated by placebo- during the N/A = not applicable. headache phase, controlled drug studies. Forty-five per- 76 and 20% during cent to 100% of patients had nausea the postdrome prior to treatment, which was similar phase. contribute to migraine-related disabil- to prevalence rates observed in other ity. Gastrointestinal disturbances are studies of adult migraineurs. The preva- often the most distressing symptoms. lence of vomiting was much lower Anorexia is common, but food cravings and varied dramatically from study to can occur; nausea occurs in 90% of study. Photophobia occurred in more patients and vomiting in about one than 85% of patients, while phonopho- third. Gastroparesis may contribute to bia was slightly less common. gastrointestinal distress and poor ab- Nausea and vomiting also interfere sorption of oral medication. Diarrhea with medication ingestion and were occurs in about 16% of patients. Many among the principal reasons for a pa- migraineurs have enhanced sensory tient’s discontinuing a specific migraine perception or sensitivity manifested medication. Gastric emptying can be by photophobia, phonophobia, and os- delayed and oral drug absorption im- mophobia, and they seek a dark, quiet paired during an attack of migraine,

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS: and vomiting may result in drug loss, justified. In patients with motor weak- A Following the thereby compromising the therapeu- ness, 47% had a family history of headache, the tic effectiveness of orally administered migraine; 18% had a family history of patient may drugs. A recent study has demon- hemiplegic migraine. The average age have impaired strated that gastric emptying may be of onset of hemiplegic migraine may concentration delayed interictally compared with be earlier than that of migraine with- or feel tired, controls (Aurora et al, 2006). out aura, while the attacks themselves washed out, Nasal congestion is common in mi- are frequently precipitated by minor irritable, and graine. Most patients with migraine en- head injury. Changes in consciousness listless. dorse nasal stuffiness during an attack. ranging from confusion to coma are a A The differential Among persons who believe they have feature, especially in childhood, and oc- diagnosis of sinus headache, a large preponderance curred in 23% of the series of Bradshaw hemiplegic actually have migraine or ‘‘probable and Parsons (1965). The prevalence of migraine includes migraine.’’ Nasal congestion may be both familial and sporadic hemiple- focal seizures, prominent in persons with migraine gic migraine has been estimated at stroke, and clusterlike ocular symptoms. 0.01% (Lykke Thomsen et al, 2002). homocystinuria, Neck pain is common in patients The differential diagnosis of hemiple- and MELAS with migraine, occurring in 60% to gic migraine includes focal seizures; syndrome. 90% of migraines studied: 20% in stroke; homocystinuria; and myopa- A Familial hemiplegic the premonitory phase, 60% during the thy, encephalopathy, lactic acidosis, migraine type headache phase, and 20% during the and strokelike episodes (MELAS) syn- 1hasthe postdrome phase. In a more recent drome (Hosking, 1988). best-characterized study, neck pain preceded the head- Familial hemiplegic migraine (FHM) phenotype; ache in 61% of patients, occurred dur- is an autosomal dominant, genetically patients have ing the headache in 92%, and followed heterogenous form of migraine with associated the headache in 41% (Kaniecki, 2002). aura, with variable penetration. Three paresthesias; In an animal model, increased sensi- genes are associated with this disorder. 88% had visual tivity in the trigeminal distribution oc- Type 1 is due to a mutation of CACNIA, auras, and 44% had speech curred after stimulation of the greater a subunit of neuronal voltage gated disturbances. occipital nerve, and increased re- P/Q type channels, on chromosome Weakness sponses of the cervical nociceptors oc- 19; type 2 is due to a mutation of lasted less than + # curred after noxious dural stimulation. ATP1A2, the Na ,K ATPase pump 1 hour in 58% gene, on chromosome 1; and type 3 is of patients; Postdrome due to a mutation of SCN21A, a neu- however, it lasted Following the headache, the patient ronal voltage-gated sodium channel, 1to3hoursin may have impaired concentration or on chromosome 2. In approximately 14%, 3 to 24 77 feel tired, washed out, irritable, and 50% of cases, type 1 FHM is associated hours in 12%, listless. Rarely people feel unusually re- with cerebellar degeneration. Type 3 and between freshed or euphoric after an attack. FHM is occasionally associated with 1dayand1week Muscle weakness, aching, and anorexia epilepsy during infancy (Dichgans et al, in 16% of patients. or food cravings can occur. 2005; Ducros et al, 1997). The aura is characterized by motor MIGRAINE VARIANTS weakness of variable intensity. The syndrome includes attacks of migraine Hemiplegic Migraine without aura, migraine with typical The IHS has subdivided hemiplegic aura, and severe episodes with pro- migraine into sporadic and familial longed aura (up to several days or forms, both of which typically begin weeks), fever, meningismus, and im- in childhood and cease with adult- paired consciousness ranging from con- hood. This separation may not be fusion to profound coma. Headache

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. " MIGRAINE: SYMPTOMS AND DIAGNOSIS

KEY POINTS: may precede the hemiparesis or be manent. Retinal migraine is most likely A In 20% of absent. The onset of the hemiparesis caused by spasm of the ophthalmic unselected families with may be abrupt and simulate a stroke. artery. Alternatively, spreading depres- familial hemiplegic FHM type 1 has the best character- sion of retinal neurons could explain migraine, patients ized phenotype. Patients have associ- some cases. have fixed ated paresthesias; 88% had visual auras, Basilar migraine was originally called cerebellar and 44% had speech disturbances. basilar artery migraine or Bickerstaff’’s symptoms and Weakness lasted less than 1 hour in syndrome. Although originally believed signs such as 58% of patients; however, it lasted 1 to to be mainly a disorder of adolescent nystagmus and 3 hours in 14%, 3 to 24 hours in 12%, girls, it affects all age groups and both progressive ataxia. and between 1 day and 1 week in 16% sexes, with the usual migraine female A Retinal migraine, of patients. The syndrome can change predominance. The aura generally lasts sometimes called in an affected individual over his or less than 1 hour and is usually followed ocular migraine, is her lifetime (Stewart et al, 1994). A by a headache that may be occipital. a rare condition in person who has FHM in adolescence The headache can be associated with which monocular may develop migraine with aura as an nausea and even projectile vomiting. A scotoma or adult and migraine without aura later typical hemianopic field disturbance blindness in life. can rapidly expand to involve all visual accompanies The headache can be generalized, fields, leading at times to temporary migraine contralateral (almost half), or ipsilateral blindness. The bilateral nature of many headache. to the hemiparesis. One sixth of sub- of the neurological events associated A The bilateral nature jects may have a single attack; one third with basilar migraine helps differentiate of many of the had between two and six episodes; and it from more typical migraine. The neurological events less than 50% had more than seven at- visual aura is usually followed by one associated with tacks. The longer-lasting episodes were or more of the following symptoms: basilar migraine associated with more profound weak- dysarthria, vertigo, tinnitus, decreased helps differentiate ness and tended to be less frequent in hearing, diplopia, ataxia, bilateral par- it from more their recurrence. esthesia, bilateral paresis, and impaired typical migraine. In 20% of unselected families with cognition, which, when marked, define A Thirty-eight FHM, patients have fixed cerebellar confusional migraine. The IHS criteria percent of symptoms and signs such as nystagmus for basilar migraine require the pres- persons in a and progressive ataxia. Cerebellar ataxia ence of one or more of the preceding dizziness clinic may occur before the first hemiplegic aura symptoms. have migraine, migraine attack and progress indepen- Vestibular migraine is a diagnostic while 50% of dently of the frequency or severity of entity that attempts to describe the migraineurs 78 hemiplegic migraine attacks. All of these overlap of dizziness and migraine, which have vestibular symptoms and families have been shown to be linked is not well described by IHS basilar 9% have vertigo. to chromosome 19 (Tournier-Lasserve, migraine. Thirty-eight percent of per- 1999). sons in a dizziness clinic have migraine, A Confusional Retinal migraine, sometimes called while 50% of migraineurs have vestib- migraine is ocular migraine, is a rare condition in ular symptoms and 9% have vertigo characterized by which monocular scotoma or blindness (Neuhauser et al, 2001). Conversely, a typical aura, accompanies migraine headache. Most one study found vertigo in up to 25% aheadache (which may be persons reporting monocular symp- of migraineurs (Kayan and Hood, 1984). insignificant), toms are probably unaware of symp- Typically, headache precedes vertigo and confusion, toms generated by the occipital lobe. by 10 years. Vestibular symptoms can which may When retinal migraine does occur, it is last minutes to 1 day and are loosely precede, occur monocular, occurring most commonly timed to the occurrence of headache with, or follow in young adults. Visual symptoms may (may occur separately or together). the headache. persist for days or weeks or be per- Some symptoms can last days to weeks

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS: and include chronic motion sensitivity companied by pain. These recurrent A (mal de debarquement). Nonvestibu- attacks of severe vomiting last 1 to 5 If the level of consciousness is lar symptoms may include ear pres- days. more profoundly sure, pain, and tinnitus, as well as panic disturbed in anxiety and phobic behavior (Neuhauser patients with et al, 2001). DIFFERENTIAL DIAGNOSIS confusional Confusional migraine occurs more migraine, commonly in boys than girls, with an Cerebral Autosomal migraine stupor incidence of about 5% (Hosking, 1988). Dominant Arteriopathy lasting 2 to 5 days It is characterized by a typical aura, a With Subcortical Infarcts and can occur. headache (which may be insignificant), Leukoencephalopathy A CADASIL is an and confusion, which may precede, Cerebral autosomal dominant arteri- inherited arterial occur with, or follow the headache. opathy with subcortical infarcts and disease of the The confusion is characterized by in- leukoencephalopathy (CADASIL) is an brain that was attention, distractibility, and difficulty inherited arterial disease of the brain mapped to maintaining speech and other motor that was mapped to chromosome 19 chromosome activities. Agitation, memory distur- and has since been reported in more 19 and has since bances, obscene utterances, violent than 200 families worldwide. been reported behavior, and sedation or a drugged The main clinical feature of CADA- in more than feeling can occur. The electroenceph- SIL is recurrent subcortical events, ei- 200 families alogram may be abnormal during the ther transient or permanent, that occur worldwide. attack. Single attacks are most com- at a mean age of 45 years. Migraine A All individuals mon, multiple attacks are rare, and with aura occurs earlier in life. The with symptoms attacks can be triggered by mild head vascular presentation is not constant, of CADASIL have trauma. If the level of consciousness is and other symptoms, such as dementia abnormal MRIs more profoundly disturbed, migraine or migraine with aura and depression, with extensive stupor lasting 2 to 5 days can occur. can occur. Although these symptoms symmetrical areas The differential diagnosis includes drug are usually associated with a history of increased T2 ingestion, metabolic encephalopathies of recurrent strokes, they may be a signals in the white matter and (Reye’s syndrome, ornithine transcar- prominent or the only manifestation of well-delineated bamylase deficiency, hypoglycemia), vi- the disease. Subcortical dementia asso- hypointense ral encephalitis, the postictal state, and ciated with pseudobulbar palsy is the lesions on acute psychosis. Confusional migraine second most common manifestation T1-weighted is also part of the syndrome of mi- of CADASIL, occurring in one third of images suggestive graine with white matter abnormality the overall affected family members of small infarcts linked to chromosome 19 (Chabriat and in 90% of subjects before death. It in the deep white 79 et al, 1995). is characterized by frontal-like symp- matter and basal Abdominal migraine occurs in ap- toms, memory impairment, gait distur- ganglia. Familial proximately 5% of recurrent abdominal bances, pyramidal signs, pseudobulbar hemiplegic pain in children. It may also occur in palsy, and sphincter incontinence. At- migraine is adults. The pain is typically midline, tacks of migraine with aura occur in distinguished from CADASIL by its lasts 1 to 72 hours and is associated 30% and mood disorders in 20% of earlier-onset type, with anorexia, nausea, vomiting, and/or patients (Chabriat et al, 1995; Ducros more benign pallor. It is a diagnosis of exclusion, and et al, 1997). Most of the strokes are clas- prognosis, and other gastrointestinal disorders must sic lacunar infarcts. normal MRI be considered. Seventy percent of chil- All individuals with symptoms have findings. dren with abdominal migraine have or abnormal magnetic resonance images will develop migraine within 10 years. (MRIs) with extensive symmetrical areas In contrast, cyclic vomiting, another of increased T2 signals in the white childhood migraine variant, is not ac- matter and well-delineated hypointense

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. " MIGRAINE: SYMPTOMS AND DIAGNOSIS

KEY POINTS: lesions on T1-weighted images sug- nerves. The enhancement resolves over A Ophthalmoplegic gestive of small infarcts in the deep several weeks as the symptoms abate. migraine is no longer classified by white matter and basal ganglia (Joutel Enhancement can occur in a variety the International et al, 1996). FHM is distinguished from of infectious (Lyme disease, syphilis, Headache Society CADASIL by its earlier-onset type, more coccidioidomycosis, human immuno- as a type of benign prognosis, and normal MRI deficiency virus) and noninfectious migraine and is findings. inflammatory conditions (lymphoma, now listed under The arteriopathy underlying the dis- leukemia, sarcoid, Tolosa-Hunt, Fisher the neuralgias. order is neither atherosclerotic nor am- syndrome). A lumbar puncture is needed A Using modern yloid and involves the media of small to rule out infections and neoplastic MRI, most patients cerebral arteries. However, lesions may causes. This disorder may be due to a with typical be observed to a lesser extent in viral infection of the oculomotor nerve clinical features of extracerebral arteries, including skin similar to Bell’s palsy. Contrast-enhanced ophthalmoplegic arterioles. Ultrastructural examination MRI and MR angiography are the pro- migraine have reveals abnormal patches of agranular cedures of choice in evaluating patients enhancement of osmiophilic material within the basal with oculomotor palsy. If MR shows the cisternal membranes of vascular smooth-muscle enhancement of the cisternal portion segmentofthe cells. Alternatively, a skin biopsy can be of the oculomotor nerve and lumbar oculomotor nerve diagnostic, although most diagnoses puncture is negative, a presumptive during the acute are currently made by genetic testing. diagnosis of ophthalmoplegic migraine phase. Ophthalmoplegic migraine is no can be made, but follow-up is necessary A Contrast-enhanced longer classified by the IHS as a type to be sure the symptoms resolve. If MRI and MR of migraine and is now listed under the the MR and lumbar puncture are nega- angiography are neuralgias. It characterized by at least tive, angiogram may still be necessary the procedures two attacks associated with ocular to rule out an aneurysm. of choice in cranial nerve palsy (usually the third Tolosa-Hunt syndrome is a rare, pain- evaluating cranial nerve with a dilated pupil) and ful ophthalmoplegia due to a granulo- patients with unilateral migrainous eye pain. Rarely matous inflammation of the cavernous oculomotor palsy. the fourth and sixth cranial nerves sinus. Diagnosis is based on the com- If MR shows enhancement of are involved. The duration of ophthalmo- bination of one or more episodes of the cisternal plegia is variable, from hours to months. painful ophthalmoplegia with paralysis portion of the Parasellar, retro-orbital cavernous si- of the third, fourth, and/or sixth oculomotor nus, or midcranial fossa lesion must cranial nerves, lasting an average of nerve and lumbar be ruled out. The differential diagnosis 8 weeks untreated, pain relief with puncture is includes berry aneurysm, acute sphe- corticosteroids within 72 hours, and 80 negative, a noid sinusitis, or sphenoid mucocele. exclusion of other causes, including presumptive Some cases of ophthalmoplegic mi- aneurysm, diabetes mellitus, paranasal diagnosis of graine fit the criteria for the Tolosa- mucocele, parasellar neoplasm, carotid ophthalmoplegic Hunt syndrome of painful ophthalmo- cavernous fistula, sphenoid sinusitis, migraine can be plegia (Hansen et al, 1990): spontaneous and other disorders of the cavernous made. remission, with recurrent attacks oc- sinus. CT scan, with and without A Tolosa-Hunt curring after months or years, and ab- contrast enhancement, may show an syndrome is a normal computed tomography (CT) or enlarged cavernous sinus in only one rare, painful MRI. Using modern MRI, most patients of five patients. MRI is more likely to ophthalmoplegia with typical clinical features of oph- be abnormal, showing a convex en- due to a thalmoplegic migraine have enhance- largement of the symptomatic cavern- granulomatous ment of the cisternal segment of the ous sinus by an abnormal tissue inflammation of oculomotor nerve during the acute isointense with gray matter on short the cavernous phase. Similar findings have been de- TR/TE images and iso-hypointense on sinus. scribed for the fourth and sixth cranial long TR/TE scans, which enhances

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS: after contrast injection. In some cases of patients with AH have a family A In patients with it may extend into the orbital apex and history of migraine. Flunarizine is effec- Tolosa-Hunt subtemporal fossa. The MRI findings tive in AH. syndrome, MRI disappear slowly over approximately 6 is likely to be months with corticosteroid treatment. Benign Idiopathic abnormal, Three months after successful treat- Thunderclap Headache showing a convex ment with corticosteroids, the abnor- Benign thunderclap headache is a enlargement of mal tissue, although diminished in sudden-onset headache (maximum in- the symptomatic size, is still visible on MRI. tensity in less than 30 seconds). It cavernous sinus by an abnormal usually lasts up to several hours with a Pseudomigraine With tissue isointense less severe headache lasting weeks. In Lymphocytic Pleocytosis with gray matter a significant minority it may recur. Pseudomigraine with lymphocytic pleo- on short TR/TE Attacks may be precipitated by exercise images and cytosis, also known as headache with or sexual intercourse. They may be iso-hypointense neurological deficit and lymphocyto- accompanied by nausea and vomiting, on long TR/TE sis, is a rare condition with one to a variant that has been called ‘‘crash scans, which 12 episodes of migrainelike headache, migraine.’’ Dodick (2002) has suggested enhances after weakness, sensory and visual symptoms, that this term be abandoned until the contrast injection. aphasia or confusion lasting minutes to pathogenesis of idiopathic thunderclap A Alternating hours (average 5 hours) (Pascual and headache can be elucidated and in Valle, 2003), lymphocytic pleocytosis with hemiplegia is order to avoid diagnostic complacency. characterized by 10 cells/mm3 to 760 cells/mm3, nega- Thunderclap headache may be accom- sudden, repeated tive workup, and normal brain imaging. panied by diffuse focal vasospasm in attacks of Single-photonemissionCTmayreveal very large arteries at the circle of Willis hemiplegia decreased uptake consistent with the and second- and third-order segments. involving each focal symptoms. Sensory symptoms oc- If focal symptoms or stroke accompany side alternately, cur in 78% of patients, followed by apha- the vasospasm, Call-Fleming syndrome lasting hours to sic and motor symptoms. Visual symp- is present. The differential diagnosis days and toms are relatively uncommon, occurring of thunderclap headache is listed in associated with dystonic features. in 12%. Recurrent cases have been de- Table 4-8 (Dodick, 2002). Diagnostic scribed (Pascual and Valle, 2003). evaluation includes early CT, lumbar A Benign puncture, MRI with MR or CT angiogra- thunderclap Alternating Hemiplegia phy, and venography. headache is a of Childhood sudden-onset Alternating hemiplegia (AH) is a rare, Mitochondrial Disorders headache progressive disorder that produces a (maximum 81 fixed motor deficit, retardation, and Most patients with MELAS have mi- intensity in less dyskinesias. It begins in infancy (before graine. Migraine also appears to be than 30 seconds). 18 months of age). The disorder is common in Leber hereditary optic neu- It usually lasts up characterized by sudden, repeated ropathy and myoclonic epilepsy with to several hours with a less severe attacks of hemiplegia involving each ragged red fibers. Testing for mitochondrial abnormalities in persons headache lasting side alternately, lasting hours to days weeks. and associated with dystonic features. with otherwise typical migraine has During an attack, the child is acutely not been fruitful. uncomfortable and has signs of autonomic disturbance. Other paroxysmal Migraine in Children phenomena, such as tonic spells, dys- Children frequently have migraine or tonic posturing, choreoathetosis, and TTH. Headache prevalence in 1993 nystagmus, can occur with the hemi- showed increases from about 40% at plegia or independently. Fifty percent age 6 to more than 70% by age 15.

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. " MIGRAINE: SYMPTOMS AND DIAGNOSIS

KEY POINTS: include depression, mania, anxiety, and A Thunderclap Differential panic (Table 4-9). Co-occurring (any headache may be TABLE 4-8 Diagnosis of other disorder present) and comorbid accompanied by Thunderclap disease and the presence of nonhead- diffuse focal Headache vasospasm in very ache symptoms present both therapeu- large arteries at " Acute hypertensive crisis tic opportunities and limitations. the circle of Willis " and second- and Carotid artery dissection HORMONAL FACTORS AND third-order " Cerebral venous sinus MIGRAINE segments. thrombosis Menstrual Migraine " A Most patients Idiopathic thunderclap Menstrual migraine is defined as an with MELAS headache attack occurring 1 day before and up to syndrome have " Pituitary apoplexy 4 days after the onset of menses. Pure migraine. " Spontaneous intracranial menstrual migraine is menstrual mi- A Pure menstrual hypotension graine without attacks at other times of migraine is " Spontaneous retroclival the cycle. Menstrually related migraine menstrual hematoma allows additional attacks (Headache migraine without Classification Subcommittee, 2004). Pre- " Subarachnoid hemorrhage attacks at other menstrual migraine occurs 7 days to times of the " Unruptured intracranial cycle. Menstrually aneurysm related migraine Adapted from Dodick DW. Thunderclap head- TABLE 4-9 Migraine allows additional ache. Headache 2002;42:309–315. Copyright Comorbid Disease # 2002. Reprinted with permission from Black- attacks. well Publishing. " Cardiovascular A Migraine attacks occur around the Hypertension or hypotension menses in 60% Migraine prevalence (probably under- Raynaud’s syndrome of women and estimated by overstrict criteria), equal Mitral valve prolapse exclusively during in boys and girls, was 3.9%. After this period (true puberty, the expected female predomi- Angina/myocardial infarction menstrual nance was observed. Migraine is differ- migraine) in 14%. Stroke ent in children; it is typically bilateral " Psychiatric A Women with a and often briefer. The IHS now allows history of children to have attacks as short as Depression 82 menstrual 1 hour (Headache Classification Sub- Mania migraine committee, 2004). The location of the Panic disorder typically have pain is usually frontal, and an occipital an improvement headache may be an ominous sign in Anxiety disorder of all their children, in contrast to adults. " Neurological migraine types with pregnancy, Epilepsy perhaps due to Migraine Comorbidities Positional vertigo sustained high Comorbidity is the presence of two " estrogen levels. Gastrointestinal or more disorders, the association of which is more likely than by chance. Functional bowel disorders Conditions that occur in migraineurs " Other with a higher prevalence than expected Asthma include stroke, epilepsy, mitral valve Allergies prolapse, Raynaud’s syndrome, and certain psychological disorders, which

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS: 1 day before the onset of menses. Mi- back low-dose transdermal estradiol A Menopause may graine attacks occur around the men- (known to produce steady levels of bring regression, ses in 60% of women and exclusively estrogen) led to a substantial improve- worsening, or during this period (true menstrual mi- ment (Martin et al, 2003). no change in graine) in 14%. Premenstrually the head- migraine. Migraine and Hormonal ache may be accompanied by other A features of premenstrual dysphoric dis- Contraception Combination oral orders, including mood changes, back- The oral contraceptives (OCs) that are contraceptives can induce, ache, nausea, and breast tenderness and most commonly used in the United change, or swelling. During menstruation, migraine States contain combinations of estro- alleviate is often associated with dysmenorrhea. gen and progestin and are taken 21 headache. The Menstrual migraine is most likely due to days each month. The older high- headache pattern estrogen withdrawal, which may trigger estrogen OCs had an increased risk of may become migraine attacks in susceptible women. stroke, but this risk has been signifi- more severe and/ cantly reduced with the new low- or frequent and Migraine and Pregnancy estrogen formulations. Progestin-only may be OCs are also available, as are implant- associated with Migraine may worsen in the first tri- able and injection progestins. neurological mester of pregnancy but may signifi- Combination OCs can induce, change, symptoms. cantly improve during later pregnancy. or alleviate headache. OCs can pro- A Twenty-five percent of women have Women with voke the first migraine attack, most no change. Women with a history of cardiovascular or often in women with a family history of cerebrovascular menstrual migraine typically have an migraine. Existing migraine may be risk factors or improvement of all their migraine types exacerbated, and headaches may pre- moderate to with pregnancy, perhaps due to sus- dictably occur on the days off the severe tained high estrogen levels. OC. The headache pattern may be- neurological come more severe and/or frequent and events in Migraine and Menopause may be associated with neurological migraine, especially those Migraine prevalence decreases with symptoms. The headaches may be- who smoke, advancing age. Menopause may bring come refractory to standard treatment. should regression, worsening, or no change in Generally, data from neurological or avoid oral migraine. Estrogen replacement ther- migraine clinics show an increased in- contraceptives. apy can exacerbate migraine or prevent cidence, severity, and refractoriness of natural improvement. Women with natu- migraine in OC users; however, studies ral menopause often show an im- from contraceptive clinics and general provement in their migraines while practitioners are more favorable. 83 women with surgical menopause often Women with cardiovascular or cere- worsen. Chemical menopause with a brovascular risk factors or moderate to gonadotropin-releasing hormone ana- severe neurological events in migraine, log did not alter the headache index especially those who smoke, should (product of headache frequency and avoid OCs. Progestin-only hormonal intensity) compared with the period contraception may be safer but prob- before treatment; however, adding ably aggravates headache.

REFERENCES

" Airy H. On a distinct form of transient hemianopsia. Philos Trans R Soc Lond 1871;160:247–264. Classic description of ‘‘classical’’ migraine.

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. " MIGRAINE: SYMPTOMS AND DIAGNOSIS

" Aurora SK, Kori SH, Barrodale P, et al. Gastric stasis in migraine: more than just a paroxysmal abnormality during a migraine attack. Headache 2006; 46:57–63.

" Blau JN. Migraine prodromes separated from the aura: complete migraine. Br Med J 1980;281:658–660. Important conceptual paper establishes the phases of migraine.

" Bradshaw P, Parsons M. Hemiplegic migraine, a clinical study. Q J Med 1965;34:65–85.

" Chabriat H, Tournier-Lasserve E, Vahedi K, et al. Autosomal dominant migraine with MRI white-matter abnormalities mapping to the CADASIL locus. Neurology 1995;45:1086–1091. Outlines cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) phenotype.

" Dichgans M, Freilinger T, Eckstein G, et al. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet 2005;366:371–377. Discovery of the third familial hemiplegic migraine gene but little phenomenological characterization.

" Dodick DW. Thunderclap headache. Headache 2002;42:309–315. Excellent review of thunderclap headache, giving diagnostic approach and management strategy for this fairly common complaint with many pitfalls.

" Ducros A, Joutel A, Vahedi K. Mapping of a second locus for familial hemiplegic migraine to 1q21-q23 and evidence of further heterogeneity. Ann Neurol 1997;42:885–890. Discovery of the second familial hemiplegic migraine gene.

" Fisher CM. Late-life migraine accompaniments as a cause of unexplained transient ischemic attacks. Can J Neurol Sci 1980;7:9–17. First and most complete description of this condition. An absolute classic.

" Giffin NJ, Ruggiero L, Lipton RB, et al. Premonitory symptoms in migraine: an electronic diary study. Neurology 2003;60:935–940. 84 Modern scientific look at the phenomenology of prodrome and the predictive value of symptoms for the development of headache.

" Hansen SL, Borelli-Moller L, Strange P, et al. Ophthalmoplegic migraine: diagnostic criteria, incidence of hospitalization and possible etiology. Acta Neurol Scand 1990;81:54–60. Good description of ophthalmoplegic migraine.

" Headache Classification Subcommittee. The International Classification of Headache Disorders. 2nd edition. Cephalalgia 2004;24(suppl 1):9–160. The new International Headache Society (IHS) classification revised after the 1988 version. In addition to consensus definitions, the brief discussion of some of the rarer forms of migraine and its mimics are very useful.

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. " Hosking G. Special forms: variants of migraine in childhood. In: Hockaday JM, ed. Migraine in childhood: and other non-epileptic paroxysmal disorders. Boston: Butterworth-Heinemann, 1988:35–53.

" Jensen K, Tfelt-Hansen P, Lauritzen M, Olesen J. Classic migraine. A prospective recording of symptoms. Acta Neurol Scand 1986;73:359–362. Important prospective study of aura symptom.

" Joutel A, Corpechot C, Ducros A, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996;383:707–710. Paper outlining this important entity.

" Kaniecki RG. Migraine and tension-type headache: an assessment of challenges in diagnosis. Neurology 2002;58:S15–S20. Challenges previous assumptions about neck pain and tension-type and cervicogenic headache.

" Kayan A, Hood JD. Neuro-otological manifestations of migraine. Brain 1984;107:1123–1142. Classic description of relationship between migraine and vertigo in this sparsely studied area.

" Lance JW, Anthony M. Some clinical aspects of migraine. A prospective survey of 500 patients. Arch Neurol 1966;15:356–361.

" Levy DE. Transient CNS deficits: a common, benign syndrome in young adults. Neurology 1988;38:831–836. Sobering explanation of the rate of unusual or hard to explain ‘‘spells.’’

" Lipton RB, Stewart WF, Cady R, et al. 2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: results of the spectrum study. Headache 2000;40:783–791. Important paper correlating phenomena with treatment intervention.

" Lykke Thomsen L, Kirchmann Eriksen M, Faerch Romer S, et al. An epidemiological survey of hemiplegic migraine. Cephalalgia 2002;22:361–375. 85 Important study.

" Martin V, Wernke S, Mandell K, et al. Medical oophorectomy with and without estrogen add-back therapy in the prevention of migraine headache. Headache 2003;43:309–321. Prospective (uncontrolled) headache study describing effects of oophorectomy with and without estrogen replacement provides solid information that physicians can give to patients.

" Neuhauser H, Leopold M, von Brevern M, et al. The interrelations of migraine, vertigo, and migrainous vertigo. Neurology 2001;56:436–441. Recent study of migraine and vertigo. Looks at migraine in dizziness clinic and vertigo in an outpatient setting.

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. " MIGRAINE: SYMPTOMS AND DIAGNOSIS

" Pascual J, Valle N. Pseudomigraine with lymphocytic pleocytosis. Curr Pain Headache Rep 2003;7:224–228. Useful review of this uncommon but important disorder.

" Sacks O. Migraine: understanding a common disorder. Berkeley: University of California Press, 1985. Extraordinary descriptions of the phenomenology of migraine. Sack’s unique perspective is both entertaining and challenging.

" Selby G, Lance JW. Observation on 500 cases of migraine and allied vascular headache. J Neurol Neurosurg Psychiatry 1960;23:23–32. The classic paper describing the symptoms of migraine.

" Silberstein SD, Young WB. Migraine aura and prodrome. Seminars Neurol 1995;15:175–182. Review of the symptoms of aura and prodrome. In the case of aura, it remains essentially up-to-date.

" Stewart WF, Schechter A, Lipton RB. Migraine heterogeneity. Disability, pain intensity, attack frequency and duration. Neurology 1994;44:S24–S39. Epidemiological description of episodic migraine.

" Tournier-Lasserve E. CACNA1A mutations: hemiplegic migraine, episodic ataxia type 2, and the others. Neurology 1999;53:3–4. Important review article on familial hemiplegic migraine.

" Wijman C, Wolf PA, Kase CS, et al. Migrainous visual accompaniments are not rare in late life: the Framingham Study. Stroke 1998;29:1539–1543. Phenomenological and epidemiological descriptions.