Neurology Migraine Headache Case File

Neurology Migraine Headache Case File

Eugene C. Toy, MD, Ericka Simpson, MD, Pedro Mancias, MD, Erin E. Furr-Stimming, MD

CASE 18

A 24-year-old Caucasian woman has a 12-year history of headaches. These headaches started in grade school, and the patient remembers missing school because of her headaches. She has never seen a physician for this problem. Typically, she gets one of these headaches one to two times per month. She anticipates the onset of a headache when she experiences preceding flashing lights and zigzag lines in both eyes. A pounding headache starts about 30 minutes later around one eye and temple. There is extreme nausea and occasional vomiting. If possible, she goes into a dark room to rest. Generally, the headache lasts 4 to 6 hours, but the patient feels tired and listless for the next 24 hours. The patient feels that the headache worsens with her menstrual cycle, and she notices that certain foods, especially red wine, can exacerbate her headache. Her general and neurologic examinations are normal. She reports her mother has similar episodes.

▶ What is the most likely diagnosis?

▶ What is the next diagnostic step?

▶ What is the next step in therapy?

ANSWERS TO CASE 18:

Migraine Headache                                                    

Summary: A 24-year-old Caucasian woman has a 12-year history of unilateral headaches with visual aura (scintillating scotoma). Headache is associated with extreme nausea, vomiting, and photophobia. Menses and certain foods can trigger the headaches.

• Most likely diagnosis: Migraine headaches.
• Next diagnostic step: This patient meets the clinical criteria for the diagnosis of classic migraine with aura. Treatment should be initiated, and a magnetic resonance imaging (MRI) of the brain should be considered if the patient has features inconsistent with migraines on history, an abnormal neurologic examination or is not responsive to therapy.
• Next step in therapy: Consider use of abortive migraine medications, such as one of the triptans, to help treat the headaches. If the patient’s headaches become more frequent, more severe, or last longer, she may be eligible for preventative therapy (discussed next).

ANALYSIS

Objectives

1. Know how to recognize a migraine headache and be able to distinguish it from headaches of other etiologies.
2. Understand what medications are available to treat migraine headaches.
3. Be familiar with a workup for headaches, and also be aware of other clinical disorders that have headache as a prominent feature.

Considerations

When evaluating a patient for headache, the clinical history is of critical importance. The age of onset, nature (type of pain, location, and associated symptoms or triggers), severity, and duration of the headache are important in determining what type of headache it is and how to manage it. In this case, the patient has a prior history of headaches characterized as episodic, unilateral, and pounding. The headaches are preceded by scintillating scotomas (visual aura) and are associated with nausea, vomiting, photophobia, and phonophobia. This patient’s neurologic examination has consistently been normal, and therefore her clinical history is highly suggestive of migrainous headache.

APPROACH TO:

Migraine Headaches                                        

DEFINITIONS

VASCULAR HEADACHE: A type of headache, including migraine, thought to involve abnormal function of the brain’s blood vessels or vascular system. The most common type of vascular headache is a migraine.

MIGRAINE WITH AURA: Formally referred to as classic migraine, in which the migraine begins with visual, auditory, smell, or taste disturbances, 5 to 30 minutes before the onset of pain.

MIGRAINE WITHOUT AURA: Formally referred to as common migraine, which is generally not associated with an aura.

PHOTOPHOBIA: Light sensitivity or intolerance to light.

PHONOPHOBIA: Heightened sensitivity to sound.

CLINICAL APPROACH

The cumulative lifetime prevalence of migraine is 43% for woman and 18% for men. The sex distribution of migraine in children is approximately 1:1, but women predominate in a ratio of 2:1 after puberty and 3:1 by middle age. This gender disparity is likely due to estrogen’s influence on nitric oxide levels. The onset of migraines tends to occur in adolescence to age 40. While it is not uncommon to see young children with migraine-type headaches, migraine is a diagnosis of exclusion for elderly patients presenting with new-onset headache.

The older literature divided migraine into two large subgroups: common and classic. Common migraine is now called migraine without aura, and classic migraine is now referred to as migraine with aura. About 20% of individuals with migraines experience aura, but many patients may experience both subtypes of migraine. Though the typical presentation is unilateral pain, up to 40% of adults and 60% of children experience bilateral pain.

Clinical Characteristics

Prodrome: The prodrome of migraine consists of nonspecific phenomena that can occur hours to days before the actual head pain. These symptoms can be psychological, such as depression, euphoria, and irritability, or more constitutional, such as increased urination, defecation, anorexia, or fluid retention. Often, photophobia, phonophobia, and hyperosmia accompany the prodrome. For many patients, there are precipitants or triggers of migraines, including red wine, cheese, chocolate, menses, and excess or deficit of sleep (Table 18–1).

Aura: An aura is differentiated from a prodrome in that an aura is often associated with frank neurologic dysfunction usually transient in nature. Symptoms develop gradually over minutes and last 5 to 60 minutes. Classically, it occurs before the head pain, but it can occur during the headache in some patients. Visual auras are the most common and include scotomas (partial alteration of visual field) and scintillating scotomas that include teichopsias (zigzag luminous images in the visual field), fortification spectra (flashing lights with zigzag pattern), photopsias (flashes of light), and distortion of images. The visual auras often start near the center of the visual field and slowly move toward the periphery. Sensory auras such as numbness and tingling in a limb are second most common, and aphasia and hemiparesis occur less often.

Headache pain: The headache pain in migraine occurs unilaterally in most migraineurs. It is usually located in the periorbital region and can extend to the cheek and ear. The pain can switch from side to side with different headaches. Migraine pain can occur in any place of the head and neck, including the posterior strap muscles of the cervical area. Typically, the head pain lasts at least 4 to 8 hours but can last for several days. The quality of the pain can be mild to severe and usually has a pulsating and throbbing quality. The patient often is troubled by associated symptoms. These include nausea, vomiting, photophobia, and phonophobia, and can be more disabling to the patient than the actual head pain. Physical activity exacerbates the symptoms, and patients frequently seek rest in a dark, quiet room.

The theory of cortical spreading depression has been implicated to explain the progression of symptoms. This theory is also important in seizure pathophysiology, explaining the march of symptoms seen in some seizures. The theory of cortical spreading depression suggests that as the disrupted cellular calcium homeostasis and chemical cascades propagate, trigeminal neurons signal dural vessels to release calcitonin gene-related peptide (CGRP), substance P, and neurokinin A. The

vessels become inflamed and dilated, and pain signals are sent to the brain.

EVALUATION

The evaluation of a migraine headache begins with a complete history and physical examination. If the history is consistent with the typical characteristics of migraine and the neurologic examination is normal, then appropriate medication can be prescribed before any testing is undertaken. Caution is exercised if either the history is atypical (ie, migraines in a man beginning after age 50) or if the neurologic examination is abnormal. If the physician feels that a workup is necessary, then diagnostic studies can include (1) blood studies, (2) spinal fluid examination, and (3) an imaging study.

Laboratory Studies

There are several systemic illnesses that are associated with headaches. These include vasculitis, toxic exposures, metabolic diseases, severe hypertension, and infectious diseases. Routine blood chemistries (chemistry panel and complete blood count [CBC]), human immunodeficiency virus (HIV) testing, vasculitis screen, thyroid function studies, and serum protein electrophoresis can be ordered as part of a routine blood study screening. If temporal arteritis is suspected, the patient should be referred to the emergency room to obtain an erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). If elevated, further workup can be done, including temporal artery biopsy to confirm the diagnosis.

Lumbar Puncture

A lumbar puncture (LP) should be considered in patients in whom meningitis is suspected (new-onset headaches are associated with fever, stiff neck, or altered mental status). If the diagnostic considerations include subarachnoid hemorrhage (SAH) or pseudotumor cerebri, a spinal tap should also be considered. If the LP is being done in a workup of headache, then the patient should have a scan performed before the LP is completed, except in those conditions where bacterial meningitis is a strong consideration. In those cases, the LP should be done immediately unless there is evidence of papilledema or focal neurologic deficits. It is also important to remember that bacterial meningitis is a neurologic emergency and if the LP is going to be delayed by more than 30 minutes, then the priority should be given to starting broad-spectrum antibiotics emergently while getting ready to perform the LP.

Imaging Study

Imaging is indicated in new-onset headaches, change in character of chronic headaches, and abnormal neurologic examination. If an LP is part of the plan, imaging should be done before the LP. Many practitioners will obtain neuroimaging once even in the setting of chronic headaches to rule out comorbid intracranial processes. If the history and neurologic examination do not suggest any focal findings, it would be unusual to find a significant abnormality on an imaging study. If the physician feels that an imaging study is indicated, MRI of the brain is usually ordered; however, a computed tomography (CT) scan is often adequate in the acute settings to identify any space-occupying lesion, shift in midline structures, brain herniation, or presence of subarachnoid blood. MRI studies of migraine patients often show white matter changes on the T2 and fluid attenuation inversion recovery (FLAIR) sequences called “unidentified bright objects” or “UBOs.” These have no identified clinical correlate and they do not need further workup.

Migraineurs have a higher rate of patent foramen ovale (PFO) compared to the general population. It is possible that the potential shunt allows small clots or toxins to bypass the lungs and travel to the brain, triggering headache symptoms. However, PFO closure in migraine patients remains controversial, and echocardiogram is not part of routine migraine evaluation.

Tension Headache

Tension headaches are typically bilateral, mild- to moderate-intensity headaches, with a band-like tightness and pressure quality. Tension headaches typically are not associated with nausea or vomiting and usually either photophobia or phonophobia. These may be associated with pericranial tenderness. Physical activity may help improve the headache. These often can be the trigger of a migraine, and frequently patients may have headaches of both the migraine and tension type.

SECONDARY CAUSES OF HEADACHES

There are several clinical settings where headaches play a prominent feature:

Sinusitis

The issue of whether chronic sinusitis can contribute to headaches is often controversial. Patients incorrectly assume that head pain in and above the eye is from sinus disease, and in truth of fact, the majority of these patients actually have migraine headaches. Sinus disease can trigger migraines, and some environmental migraine triggers are also triggers for sinus inflammation. If sinus symptoms do not respond to anticongestants, strongly consider migraine therapy.

Subarachnoid Hemorrhage

SAH occurs from the following: (1) leakage of an arteriovenous malformation, (2) leakage of a ruptured aneurysm, or (3) trauma. Patients with SAH often present with a debilitating headache described as the worst headache of their lives. The headache is often described as “thunderclap headache.” It is of sudden onset and can be associated with nausea, vomiting, and stiff neck. SAH can look like a migraine attack, especially if there is extreme nausea and vomiting. CT of the brain should show blood in the subarachnoid space, which is irritating to the meninges and leads to severe headache. If you have a strong clinical suspicion for SAH despite negative CT scan, an LP is indicated to look for frank blood or xanthochromic staining of the cerebrospinal fluid (CSF). Patients with SAH can decompensate quickly, and 50% of patients do not survive their subarachnoid bleed. Patients must be monitored for many days in the intensive care unit (ICU) setting due to the risk of cerebral vasospasm.

Carotid Dissection

Patients with carotid dissection often present with orbital or neck pain associated with neurologic findings suggestive of carotid disease. This is often accompanied by ipsilateral Horner syndrome: a triad of miosis, ptosis, and anhidrosis produced when the sympathetic trunk surrounding the carotid artery is damaged by the dissection. A careful history assessing for recent trauma to the neck or vigorous movements including whiplash injuries can help differentiate this neurologic emergency from a migraine.

Temporal Arteritis

In headache patients who are older than 50 years, temporal arteritis should be considered. Temporal arteritis is a granulomatous arteritis affecting medium- and large-sized arteries of the upper part of the body, especially the temporal vessels of the head. The headaches are often precipitous and can be accompanied by complaints of scalp tenderness and jaw claudication. In addition, patients may experience pain and stiffness in the neck, shoulders, back, and sometimes in the pelvic girdle. The head pain is usually one-sided and in the temporal region. The major complication of temporal arteritis is blindness. In addition to the clinical presentation, ancillary laboratory data that can help make the diagnosis of temporal arteritis include an elevated sedimentation rate, elevated CRP, and thrombocytosis. An elevated platelet count increases the risk of vision loss. A positive temporal artery biopsy can confirm the diagnosis but is not required to start therapy if you strongly suspect disease, as delaying treatment while waiting for the biopsy may result in vision loss. High-dose oral steroids are the treatment of choice.

Postspinal or Post-LP Headaches

Approximately 25% of patients will have a headache after LP. These headaches are almost always better when lying down and worsen with sitting or standing up and can be associated with nausea and vomiting. These can occur with either a traumatic or an atraumatic tap. They generally improve over time with bed rest and fluids. For those post-LP headaches that do not improve, an epidural blood patch (small injection of the patient’s blood injected into the epidural space) at the site of the original spinal tap can be therapeutic.

Pseudotumor Cerebri

Pseudotumor cerebri (idiopathic intracranial hypertension) is manifested by increased intracranial pressure without evidence of a central nervous system (CNS) malignancy or other abnormality. Patients with idiopathic intracranial hypertension complain primarily of headaches often associated with visual disturbances. Transient visual obscurations (ie, sudden graying of vision) may occur, particularly when the patient stands up quickly. Papilledema is classically seen on the examination, and untreated disease can lead to blindness. Pseudotumor cerebri is usually seen in female patients who are obese and often have menstrual irregularities. First-line treatments include weight loss, acetazolamide to decrease CSF production, and a limited number of LPs. If conservative treatments fail, second-line treatments include placing a ventriculoperitoneal shunt or optic nerve fenestration to relieve the pressure, and nerve edema may be necessary to help preserve vision.

Acute Glaucoma

Acute angle-closure glaucoma is often characterized by sudden orbital or eye pain in the face of nausea and vomiting. The eye often will tear profusely and conjunctiva become injected. The cornea may swell and take on a cloudy appearance. Visual changes would be expected to occur only in the affected eye, as opposed to the binocular visual changes seen with migraine. The pain can begin after the use of anticholinergic drugs. Though the pain could appear similar to a migraine, patients will often report that the eye pain exceeds the headache pain. An elevated intraocular pressure (IOP) is the hallmark of acute angle-closure glaucoma, and it is important to measure IOPs when acute glaucoma is suspected in order to start treatment and preserve vision in that eye.

Brain Tumor

Headaches associated with brain tumors often present as typical tension or migraine headaches. The headaches can be quite frequent and can occur on a daily basis, often awakening the patient from sleep. Neurologic examination can be normal but can reveal focal abnormalities as well as papilledema on funduscopic examination. Headaches are the presenting feature in approximately 40% of brain tumor patients.

THERAPY AND MANAGEMENT OF MIGRAINE HEADACHES

Abortive Treatment

The treatment of an individual migraine attack once it has occurred is referred to as abortive therapy. Treatment should be started at the earliest sign of the headache or as soon thereafter as possible.

Many patients likely will have already attempted some nonspecific pain relief medications prior to presentation in clinic. Options include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, indomethacin, diclofenac, ketoprofen, and acetylsalicylic acid. These medications often are the first line in treatment due to easy access without prescription and/or low cost. However, not all migraines will respond to these medications, and overuse can lead to rebound headaches.

There are several medications referred to as triptans that are approved for first-line abortive therapy of moderate to severe migraine. These include sumatriptan, almotriptan, rizatriptan, zolmitriptan, eletriptan, naratriptan, and frovatriptan. These drugs are available in various oral, nasal spray, and intramuscular formulations. The drugs work as 5HT-1B and 5HT-1D serotonin receptor agonists. These drugs are 80% effective in the treatment of an individual migraine attack. They should be used early in the headache, such as during the prodrome, but they can also be used once the headache has started. The drugs can be repeated as early as 4 hours in headache reoccurrence, but no more than three doses per 24 hours should be used. The side effect profile of the triptans is similar and includes occasional nausea, vomiting, and numbness and tingling of the fingers and toes. Clear-cut contraindications to the use of triptans include a history of coronary artery disease or hypertension. If the patient has hemiplegia or blindness as an aura in a migraine attack, then triptans should not be used.

Ergotamines are no longer the cornerstone of the abortive treatment of migraine but may be tried if triptans fail. Ergotamines agonize serotonin receptors and interact with many other receptors. Side effects include vasoconstriction and nausea. Dihydroergotamine (DHE) is the only widely used ergotamine. Antiemetics such as metoclopramide or prochlorperazine can be added if nausea is present. Repeat doses over several days may be used for severe or prolonged attacks (ie, status migrainosus). DHE is available in both intravenous (IV) and intranasal forms.

Midrin is a medication that spans the gap between abortive and prophylactic therapy. The drug consists of three components: acetaminophen (a simple analgesic), dichloralphenazone (a muscle relaxant), and isometheptene mucate (a vasoconstrictor). If Midrin is used in an abortive fashion, patients are instructed to take two tablets at the onset of a headache or aura, then one tablet hourly for three additional doses (five tablets total). The drug can also be used as a prophylactic agent for muscle tension headaches by taking one tablet twice a day scheduled, and then a third or even a fourth pill for a breakthrough headache during that day.

Evidence for using corticosteroids is very limited, but using a single dose with intractable migraine may reduce recurrence after the acute episode is aborted without providing additional benefit for acute relief from the headache.

Combinations of medications are often used for the abortion of an acute migraine attack. Dopamine antagonists such as antiemetics or antipsychotics (eg, droperidol and prochlorperazine) in addition to NSAIDs, antihistamines (eg, diphenhydramine), IV magnesium, and/or antiepileptics (valproic acid) are often used. These agents have been shown to be as effective as triptans when used alone or in combination. In a few cases, opioids can be used for acute pain relief, but their use should be limited to avoid rebound headache. It is also important that IV hydration is important with nausea and vomiting.

Prophylactic Treatment

The first step in treating and preventing migraines is lifestyle modification. Patients should keep a headache diary to help them identify triggers and then work toward avoiding known triggers whenever possible (see Table 18–1).

Prophylactic treatment is indicated when there are at least three attacks per month or if acute therapy is not effective. Consider the individual patient and the headache frequency, duration, severity, and level of impairment. Prophylactic therapy is underused but can prevent the incidence of transformed migraine (occasional migraines become chronic daily headaches) and medication overuse headaches. At least 25% of migraine patients may be candidates for prevention therapy. Options include anticonvulsants (topiramate, divalproex. and gabapentin), beta-blockers (propranolol), calcium channel blockers (verapamil), and antidepressants (duloxetine, amitriptyline, and nortriptyline). Other medications used in migraine prevention, but as second-line agents, include methysergide maleate (not available in United State), lithium carbonate, clonidine, and captopril.

Currently, anticonvulsants are prescribed most frequently in the prophylactic treatment of migraine. Patients typically respond at lower doses than used for seizure therapy, and there is no need for routine monitoring of blood levels. Topiramate is widely used, but side effects include perioral numbness and tingling in the fingers and toes, kidney stones, and cognitive slowing. Rarely, it can cause angle closure glaucoma. Slow titration on the dose helps prevent cognitive complaints. Divalproex has also been used successfully to treat migraine. Side effects include alopecia and tremor.

Beta-blockers have been used in the prophylactic treatment of migraine since 1972. The most commonly prescribed beta-blocker is propranolol. The long-acting form is often prescribed. Once a beta-blocker has been instituted, there can be a slight decrease in blood pressure and pulse. The major side effects seen with beta-blockers are depression, fatigue, alopecia, bradycardia, hypotension, cold extremities, and postural dizziness. From a practical standpoint, in a population of migraineurs who are generally young and female, beta-blockers are often difficult to tolerate and are used when other groups of medications have failed. Beta-blockers can be particularly useful if the patient has a second indication to use beta-blockers, such as hypertension.

Injection therapies may also be used to prevent migraines. OnabotulinumtoxinA (Botox) is the only FDA-approved therapy for chronic migraines. It is injected in a series of injections in the frontal, temporal, and occipital regions every 3 months. Occipital nerve blocks of steroid and local anesthetic may also be used to help prevent migraines triggered by inflammation of the occipital nerves. While individual patients report improvement, randomized clinical trials show no difference between occipital nerve blocks and placebo for migraine prevention.

CASE CORRELATION

• See Case 12 (Subarachnoid Hemorrhage)

COMPREHENSION QUESTIONS

For each clinical presentation 18.1 to 18.4, choose the most appropriate diagnosis from the following list:

A. Subarachnoid headache

B. Sinusitis

C. Post-LP headache

D. Carotid dissection

E. Pseudotumor cerebri

F. Migraine with aura

G. Migraine without aura

18.1 A 38-year-old man presents with right-sided neck pain, right mydriasis, ptosis, and anhidrosis. He also has left-sided numbness of the face, arm, and leg after a wrestling match with his son, in which his neck was twisted.

18.2 A 37-year-old obese woman presents with 2 weeks of persistent headache associated with blurry vision, especially when she stands up quickly or strains.

18.3 A 21-year-old college student studying for final examinations complains of recurrent right temple pain, preceded by flashing lights, and followed by nausea lasting 3 to 5 hours.

18.4 A 54-year-old man underwent a spinal tap 2 days prior for evaluation of chronic bilateral foot numbness and weakness. He now complains of a significant headache and nausea when he rises from a supine (lying flat) to an upright position.

ANSWERS

18.1 D. Carotid dissection is the most likely explanation in this case since the pain is mainly of the neck and associated with contralateral neurologic findings. Horner syndrome (mydriasis, ptosis, and anhidrosis) is due to the disruption of the sympathetic plexus surrounding the carotid artery. Acute admit for stroke team evaluation is the next step.

18.2 E. Pseudotumor cerebri is the most likely cause of headache in this patient, but other intracranial lesions as cause of new-onset headache must be ruled out first. The patient needs ophthalmology evaluation, imaging, and lumbar puncture.

18.3 F. This is the typical presentation of migraine with aura, with unilateral headache associated with nausea. Abortive therapy can be started if the history and physical do not suggest any underlying systemic or neurologic disorders.

18.4 C. Post-LP headache is likely caused by the proximal relationship to the LP. He may have an inflammatory neuropathy as the cause of his baseline neurologic symptoms, but this would be unrelated to the new-onset headache.

    CLINICAL PEARLS    

▶ Migraine is a common disorder, yet it is an underdiagnosed and undertreated neurologic disease. ▶ Migraine aura classically precedes the headache but can occur before or during the headache. Some individuals may experience an aura without any pain. ▶ Always consider the secondary causes of headache when evaluating a new patient with headaches, checking for red flags and signs/symptoms such as papilledema and early morning headaches. ▶ Patients may have more than one type of headache. ▶ Consider prophylactic treatment of migraine headaches that cause significant impairment to daily life due to frequency, duration, and/or severity.

REFERENCES

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Dilli E, Halker R, Varga B, et al. Occipital nerve block for the short-term preventive treatment of migraine: a randomized, double-blinded, placebo-controlled study. Cephalalgia. 2015;35(11): 959-968. 

Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9): 629-808. 

Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 1: triptans, dihydroergotamine, and magnesium. Headache. 2012;52(1):114-128. 

Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others. Headache. 2012;52(2):292-306. 

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Richer L, Billinghurst L, Linsdell MA, et al. Drugs for the acute treatment of migraine in children and adolescents. Cochrane database Syst Rev. 2016;4:CD005220. 

Rizzoli PB. Acute and preventive treatment of migraine. Continuum (Minneap Minn). 2012;18(4): 764-782. 

Saper, JR, Silberstein SD, Gordon CD, et al. Handbook of Headache Management, a Practical Guide to Diagnosis and Treatment of Head, Neck, and Facial Pain. Baltimore, MD: Williams & Wilkins; 1993. 

Silberstein SD, Lipton RB, Goadsby PJ. Headache in Clinical Practice. London, UK: Martin Dunitz; 2002. 

Ward TN. Migraine diagnosis and pathophysiology. Continuum (Minneap Minn). 2012;18(4):753-763.

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