Headache is a nearly universal experience, as over 90% of individuals have noted at least one headache during their lifetime. Since sensory information from the eye and orbit travels through the ophthalmic division of the trigeminal nerve, many headache syndromes are associated with pain concentrated around the eye. Furthermore, many primary headaches syndromes have prominent neuro-ophthalmic signs and symptoms. Thus, the reader should become familiar with the many types of headache, facial pains, and disorders of facial sensation.
History . The cause of the patient’s headache is usually established from the history. Important features include the frequency, location, laterality, mode of onset, duration, nature of the headache, and the presence of accompanying symptoms along with precipitating and alleviating factors. Visual aura is highly suggestive of a migraine disturbance. Although nonspecific, photophobia, phonophobia, osmophobia, and gastrointestinal symptoms may also help to discriminate migraine from other causes of headache. The patient’s medical and psychiatric history and medication list provide essential information.
Classification . It is useful to classify headaches into those that are primary (or without specific cause) and those with an organic cause. Migraine, tension-type, and trigeminal autonomic cephalgias are the most common forms of primary headache. The International Headache Society (IHS) has established diagnostic criteria for a variety of headache disorders to provide uniformity in classification ( Boxes 19.1–19.4 ).
Five attacks fulfilling criteria B–D
Headache lasting 4–72 hours (untreated or unsuccessfully treated)
Headache has 2 of the following characteristics:
Moderate to severe intensity
Aggravation by or causing avoidance of routine physical activity
During headache at least 1 of the following:
Nausea and/or vomiting
Photophobia and phonophobia
Not attributed to another disorder
At least 2 attacks fulfilling criteria B–C
One or more of the following fully reversible aura symptoms:
Speech and/or language
At least 2 of the following 4 characteristics:
At least one aura symptom develops gradually over ≥5 minutes and/or two or more symptoms occur in succession
Each individual aura symptom lasts 5–60 minutes
At least one aura symptom is unilateral
The aura is accompanied, or followed within 60 minutes, by headache
Not better accounted for by another ICHD-3 diagnosis, and transient ischemic attack has been excluded
At least 10 episodes of headache occurring on 1–14 days per month on average for >3 months (≥12 and <180 days per year) and fulfilling criteria B–D
Lasting from 30 minutes to 7 days
At least 2 of the following 4 characteristics:
Pressing or tightening (nonpulsatile) quality
Mild or moderate intensity
Not aggravated by routine physical activity such as walking or climbing stairs
Both of the following:
No nausea or vomiting
No more than one of photophobia or phonophobia
Not better accounted for by another ICHD-3 diagnosis
At least five attacks fulfilling criteria B–D
Severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15–180 minutes (when untreated)
Either or both of the following:
At least one of the following symptoms or signs, ipsilateral to the headache:
Conjunctival injection and/or lacrimation
Nasal congestion and/or rhinorrhea
Forehead and facial sweating
Forehead and facial flushing
Sensation of fullness in the ear
Miosis and/or ptosis
A sense of restlessness or agitation
Attacks have frequency between 1 every other day and 8 per day for more than half of the time when the disorder is active
Not better accounted for by another ICHD-3 diagnosis.
These guidelines were primarily created for the purpose of collecting epidemiologic and clinical trial data and may not be practical for use in the clinical setting. Diagnostic difficulty occurs because some patients have multiple headache syndromes and because headache characteristics can change. Additionally, the restrictive IHS requirements for a minimum number of headaches with a certain duration may exclude individuals who likely do have that headache type.
“Red-flag” headache characteristics suggesting a more ominous underlying cause are listed in Box 19.5 . These headaches require more aggressive evaluation, including neuroimaging and possibly lumbar puncture.
Association with fever, coughing, straining, or sexual activity
Change with position, cough, or exertion
Focal neurologic symptoms or signs
Onset after the 4th decade
Onset during pregnancy or postpartum
Underlying disorder such as cancer or human immunodeficiency virus
This section reviews the epidemiology, genetic and clinical factors, pathophysiology, and treatment of migraine.
Approximately 18% of women and 6% of men endure recurrent headache classified as migraine. Migraine prevalence is highest among 30–50-year-olds, with more white than black people and with an inverse relationship to income. Nearly 90% of patients with migraine report some disability associated with their headache, with half having severe disability. Patients with migraine may lose several days of work per year related to headache. Despite the high frequency of disability associated with migraine, many patients do not seek medical attention and rely on over-the-counter medications, with many probably inadequately treated. Patients with episodic migraine may develop a chronic disease state, formerly termed transformed migraine, but now called chronic migraine, characterized by 15 or more headaches per month.
Many neurologic and psychiatric disorders may have an association with migraine. According to one study, epilepsy patients have twice the risk of developing migraine than those without epilepsy and may have a shared genetic susceptibility. There is a higher incidence of stroke in patients with migraine, particularly in those with aura. Silent posterior circulation infarcts have been documented in migraine patients. Nonspecific deep white matter lesions on are commonly seen on magnetic resonance imaging (MRI), and there may be lesion progression, but their exact pathogenesis is unclear. Various affective disorders are related to migraine, including depression, manic depressive illness, and panic disorder. Cosensitization may explain the association of chronic migraine with depression and anxiety.
Genetic factors . A genetic basis for migraine is suggested by the observation that 70–90% of migraine patients have a positive family history. Migraine has been linked to chromosomes 1 and 19, with familial hemiplegic migraine (FHM) type 1 linked to chromosome 19. The defective gene likely encodes for a voltage-dependent P-type calcium channel. Chromosome 19 has also been linked to CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), an autosomal dominant arteriopathy characterized by leukoencephalopathy, subcortical infarction, and migraines. Other studies of FHM suggest additional loci including FHM type 2 caused by a mutation in the gene ATP1A2 and FHM type 3 linked to a mutation in gene SCNA1A. Accumulating data suggest that migraine may be a channelopathy, a condition that ultimately leads to neuronal hyperexcitability.
Pain-sensitive structures of the head and face include the skin and blood vessels of the scalp; dura; venous sinuses; arteries; and sensory fibers of the fifth, ninth, and tenth nerves . Although the mechanism of migraine remains uncertain, evidence suggests an important role for the trigeminal vascular projections and the neurochemical serotonin. The trigeminal nerve has terminals on the pial and dural blood vessels that release a variety of vasoactive neuropeptides, including substance P, neurokinin A, and calcitonin gene-related peptide (CGRP). Release of these neuromediators produces sterile neurogenic inflammation by dilating meningeal blood vessels and increasing vascular permeability. Sumatriptan and dihydroergotamine (DHE) act on presynaptic 5HT 1 D receptors, blocking the release of these neuroactive peptides and 5HT 1 B receptors to selectively constrict dilated meningeal vessels. Additionally, 5HT 1 B/D agonists such as the triptans that cross the blood–brain barrier may also block neurons of the trigeminal nucleus caudalis within the medulla.
Evidence for the involvement of brainstem structures is supported by positron emission tomography studies that show increased blood flow in the reticular activating formation during the migraine episode. The median raphe nucleus, the periaqueductal gray matter, and the locus ceruleus are regions thought to be activated during a migraine. Activated parasympathetic projections from the superior salivatory nucleus may produce vasodilation of meningeal vessels.
Mechanism of migraine aura . While classic explanations for migraine attributed the aura to vasoconstriction and the headache to vasodilation, contemporary theories suggest otherwise. For instance, blood flow studies have demonstrated reduced flow preceding the onset of the aura but continuing into the headache phase, which would be during a period of vasoconstriction. The aura of migraine is thought to be related to the concept of a spreading cortical depression, which was promulgated by Leão, who demonstrated that electrical depression moved over the cortex at a rate of 2–3 mm per minute. Leão’s observation was supported by Lashley, who calculated his own aura progressing over the visual cortex at the same rate of 2–3 mm per minute. Although blood flow reduction spreads over the cortex at this rate, current thinking attributes this to a secondary event triggered by a primary neurogenic process. Perfusion-weighted imaging, positron emission tomography, magnetoencephalography, and functional MRI support the notion of cortical spreading of oligemia and neuronal depression.
Lance proposed that the neuroadrenergic locus ceruleus, which diffusely projects to the cerebral cortex, may be one neural network involved in the generation of migraine aura. Activation of the locus ceruleus has been implicated in the development of photophobia and phonophobia. Ultimately, the locus ceruleus and the spinal nucleus of the trigeminal nerve are influenced by the cortex and other higher structures. Functional MRI studies suggest that the red nucleus and substantia nigra may also be involved in this neural network. Cortical spreading depression (CSD) may release a variety of substances in the cortex via neuronal channel opening and parenchymal inflammatory cascades, such that suppressing these events have abolished CSD-induced trigeminal vascular activation, mast cell granulation, and headache. How aura and headache are related mechanistically remains uncertain.
Integrated theory . Presently, the precise pathophysiology of migraine remains uncertain, but a cascade of events seems likely. In summary, migraine appears to be initiated by hyperexcitability of cortical and brainstem neurons ( Fig. 19.1 ). The overactivation of these neurons may result from an underlying channelopathy seen in genetically predisposed individuals. Presumably, these hyperexcitable neurons are responsible for activating portions of the cortex (aura) and meningeal vessels (pain). The firing of these hyperexcitable neurons may be influenced by internal and external factors such as hormonal balance, food, stress, and sleep deprivation. The different symptoms observed in migraine probably reflect differential activation of cortical, brainstem, and vascular structures.
In some patients, the migraine process persists, and central sensitization occurs. Continued peripheral sensory input can lead to sensitization of central (second order) trigeminovascular neurons and third-order neurons in the thalamus. The centrally based pain neurons may continue to propagate pain impulses even in the absence of further input from the peripheral trigeminal neurons. Clinically, the patient may develop cutaneous allodynia, during which normally nonpainful tactile stimuli become painful. Such patients may experience localized pain with routine activities such as wearing eyeglasses, combing hair, or taking a shower. In this stage, the patient’s pain may be refractory to triptan therapy. Chronic migraine may result from repeated episodes of cutaneous allodynia.
Symptoms and Signs
A variety of factors may provoke migraine, including menstruation, change in sleep patterns, hunger, stress, certain foods, odors, and even the type of lighting. Hours to days before the onset of migraine, the patient may experience prodromal symptoms manifesting as mood swings, food cravings, anorexia, fluid retention, or urinary frequency.
Headache . The headache of migraine is usually unilateral, throbbing, and of moderate severity (see Box 19.1 ). It may start any time but has a tendency to start in the morning. The onset is usually gradual, and this feature helps to distinguish migraine from more ominous causes such as a subarachnoid hemorrhage. Headaches usually last several hours and may be exacerbated by physical activity. The headache may pass through stages ranging from mild to severe. Various symptoms may accompany the headache, including photophobia, phonophobia, osmophobia, nausea, vomiting, and autonomic symptoms (see Box 19.1 ). Patients may also become irritable, anxious, or depressed during the headache phase.
Aura . The aura of migraine usually begins before the headache, but occasionally it will occur simultaneously or follow it (see Box 19.2 ). Approximately one-third of migraine patients experience an aura. Classically, the aura is visual, but sensory dysfunction may occur. Visual symptoms crescendo over several minutes and resolve by 30 minutes but occasionally will extend to 60 minutes. Some patients will have recurrent auras. Many patients cannot determine whether the phenomenon occurred monocularly or binocularly. Often patients believe a hemifield disturbance occurred in one eye. Although fortification scotomas are the characteristic visual disturbance, patients may also describe bright flashing lights or distorted vision. Some patients describe their vision as looking through clouded or prismatic glass. Classically, an arc of flashing zigzag light starts in the paracentral area of one hemifield and expands peripherally. As the wave of visual disturbance travels across the visual field, it may rotate or undulate. Other patients describe tunnel vision or a bilateral hemifield disturbance. Unusual visual illusions may occur, such as palinopsia (perseveration of visual images) or the Alice in Wonderland syndrome. In the latter, the patient may appreciate objects as overly large, small, distorted, close, or far.
Rarely, patients have persistent positive visual phenomena. The neuroimaging does not show any evidence of infarction, and the aura symptoms persist beyond 1 week. Various types of positive visual aura are discussed in greater detail in Chapter 12 , and the negative visual auras (vision loss) in Chapter 10 .
Sensory disturbance may include paresthesias, dysesthesias, numbness, or hyperesthesia, and these sensory symptoms may follow the headache. Classically, the sensory symptoms begin in the fingertips and march up the arm into the perioral area. Sensory auras are most convincingly migraine when preceded by a classic visual aura. Language and motor auras are uncommon, but their initial occurrence should prompt investigation for transient cerebral ischemia.
Interictal Heightened Visual Sensitivity
Between episodes of headache, migraineurs may have a heightened sensitivity to bright lights, glare, and other visual stimuli. Patients may complain of sensitivity to flickering lights (strobe and fluorescent), patterned stimuli, moving objects, and supermarket aisles (visual vertigo). These visual stimuli may cause headaches, perhaps in part by lowering trigeminal and cervical pain thresholds. Migraineurs may have impaired inhibitory subcortical function that normally suppresses glare-induced pain. Alternative explanations include primary visual cortex and V5 hypersensitivity or reduced inhibition by extrastriate structures. Detailed psychophysical and electrophysiologic studies have also demonstrated that interictal visual function may be subtly altered in migraineurs.
The term migrainous infarction refers to migraine aura symptoms associated with a permanent neurologic deficit (visual, motor, or sensory) during the course of a typical migraine with aura attack. MRI may demonstrate the cerebral ischemic changes that typically occur in younger women and in the occipital–parietal regions ( Fig. 19.2 ).
While there is no effective therapy for evolving migrainous infarction, we treat with high-dose intravenous methylprednisolone and hydration. Triptan medications should be avoided because of their vasoconstrictive properties. Sublingual calcium channel blockers may reduce vasospasm, but this beneficial effect must be weighed against possible hypotension.
Retinal migraine events typically occur in one eye. Unlike a migraineur with occipital auras, patients with retinal migraine frequently experience a negative visual phenomenon described as a graying or blackout of vision. Visual loss is often described as a tunnel but may be altitudinal or quadrantic. The diagnosis of retinal migraine is one of exclusion, and migraine is suggested as a rare cause of transient or permanent visual loss.
Observers have noted constriction of the retinal arterioles and venules during an attack whereby the retina transiently loses its orange color. Likely, the retinal changes are primarily induced by local vascular changes. Rarely, patients have permanent visual loss as the result of retinal or optic nerve damage ( Box 19.6 ). Of patients with permanent visual loss, most did not meet diagnostic criteria for retinal migraine and likely represented a heterogenous group of underlying ophthalmic disorders.
Anterior ischemic optic neuropathy
Central retinal artery occlusion
Branch retinal artery occlusion
Central retinal vein occlusion
Retinal pigment changes
Central serous chorioretinopathy
The evaluation of patients with retinal migraine includes noninvasive studies of the carotid arteries and checking for antiphospholipid antibodies. Echocardiography and a hypercoagulable workup may be needed to exclude a nonmigrainous cause. Calcium blockers have been particularly effective for these patients. Occasionally, an aspirin a day will a reduce retinal migraines.
This entity and other types of transient visual loss in migraine are also discussed in Chapter 10 .
Ophthalmoplegic Neuropathy (Ophthalmoplegic Migraine)
Ophthalmoplegic neuropathy is a rare disorder that usually begins before age 10 years in a patient with a typical migraine pattern. Previously this entity was labeled ophthalmoplegic migraine, but this term has been replaced because the syndrome is considered a recurrent painful neuropathy. Typically, the ophthalmoplegia follows the headache by several days, but occasionally it will occur simultaneously or precede it. Common motility disturbances include a third nerve palsy, with pupillary involvement in nearly 50% of patients, and rare involvement of fourth and sixth nerve palsies or a combination of ocular motor palsies. Other causes of a cavernous sinus syndrome need to be excluded. The ophthalmoparesis usually resolves after 1–4 weeks. After several episodes, a partial palsy may persist.
In patients younger than 10 years, MRI and magnetic resonance angiography (MRA) suffice to exclude most serious conditions when a pupil-involving third nerve palsy is present. In most patients, transient third nerve enhancement and nerve thickening are observed. After age 10 years, an aneurysm is a concern and should be excluded.
The cause of the ophthalmoparesis is uncertain. While the theory of a recurrent demyelinating cranial neuropathy has become popular, the etiology is unknown, and the cerebrospinal fluid (CSF) is typically normal. It is debated whether the inflammation of the third nerve activates the trigeminally innervated third nerve sheath or whether the inflammation of the adjacent circle of Willis extends to the third nerve. The latest ICHD classification (3rd edition) for ophthalmoplegic neuropathy requires the exclusion of orbital, parasellar, or posterior fossa lesions. We typically use a short course of oral prednisone in these patients. There is no solid evidence that preventive therapy alters the course of this disorder.
This entity is also discussed in Chapter 15 .
Benign Episodic Mydriasis
Rarely, an intermittently or permanently dilated pupil may be a manifestation of migraine, when other signs of a third nerve palsy or acute-closure glaucoma are absent. This entity is discussed in Chapter 13 .
Migraine With Brainstem Aura (Basilar Migraine)
Patients who experience migraine with a brainstem aura may experience transient symptoms of posterior circulation insufficiency, including visual field defects, vertigo, nystagmus, ataxia, impaired hearing, dysarthria, and motor and sensory symptoms. Some patients experience an alteration of consciousness, presumably stemming from the reticular activating system. It usually occurs in young women and may be the cause of episodic vertigo seen in young children. These patients may be more sensitive to the vasoconstrictive effects of triptan medication. Thus, triptan compounds are contraindicated in these patients. Unfortunately, solid data regarding this issue are lacking.
Hemiplegic migraine usually occurs early in life as a prelude to headache. It has a male predominance and may be familial. The hemiplegia usually lasts less than 1 hour, but it may persist for several days. Like the sensory aura, the headache may precede the hemiplegia. These patients may be sensitive to the triptan compounds, and their use in this subgroup of patients should be avoided until further data are available.
Patients with migraine commonly have vertigo. For some, episodic vertigo may be the only complaint. Confusion may exist with Ménière’s disease, and the two entities may coexist. Although phonophobia is common in migraine, some patients may experience acute permanent hearing loss. The vertigo may begin abruptly, lasts from seconds to days, and can be severe. Vestibular migraines commonly occur without headache. Patients may experience abnormalities on vestibular testing, including caloric paresis, spontaneous nystagmus, positional nystagmus, and abnormal rotary-chair testing. Patients may have nystagmus that can suggest either a central or peripheral vestibular disorder. Baloh proposed that such patients may have a defective calcium channel manifesting within the inner ear and brain. The treatment is similar to that for other forms of migraine.
Migraine in Women
Menstrual migraine . Migraine associated with menses is extremely common in women, and the likely pathogenesis is falling serum estrogen levels contemporaneous with the onset of bleeding. Many women can predict their headaches in relationship to the onset of menses. Typically these migraines are more severe, longer lasting, and more difficult to treat than nonmenstrual migraines. Generally, they are unassociated with auras.
Migraine in pregnancy . While some women suffer from worsening of their migraines during pregnancy, others, for unclear reasons, enjoy vast improvement. Most prophylactic and abortive migraine medications except acetaminophen are contraindicated in pregnancy.
Oral contraceptives and stroke in migraine . Controversy surrounds the use of oral contraceptive medication in women who suffer from migraine with aura. Migraine with aura itself may increase the risk of ischemic stroke in women of childbearing age, and the use of oral contraceptives may enhance this risk. The absolute risk is still low. The risk of stroke may be most significant in female migraineurs who are older than 35 years, use contraceptives, and smoke cigarettes. Some neurologists allow the use of contraceptives without estrogen in young women with migraine with aura but avoid the use of any contraceptive in women with migraine with aura who are refractory to treatments, smoke, or are older than 35 years. Gynecologists may be more restrictive and not permit any oral contraceptive use in woman with migraine, with or without aura.
Diagnostic Testing in a Patient With Suspected Migraine
Visual fields should be assessed in all new patients with suspected migraine visual aura to exclude field defects. A homonymous defect, for instance, would suggest alternative diagnoses such as release hallucinations or seizures due to a neoplasm.
In patients with a long history of typical migraine and a normal examination, it may be reasonable to defer neuroimaging. However, we have a low threshold for performing MRI in most patients, because there are many causes of headache, and several organic disorders may mimic or trigger migraine, particularly in patients with new onset of symptoms in middle age, atypical features, or marked increase in frequency of headache (see Box 19.5 ). Routine blood work is often unhelpful in young patients, but an erythrocyte sedimentation rate and C-reactive protein is critical in elderly patients with transient loss of vision or headache to help exclude temporal arteritis. Lumbar puncture, obtained after neuroimaging, is an important test when a subarachnoid hemorrhage, meningitis, or pseudotumor cerebri syndrome is suspected.
Migraine treatment depends on the characteristics of the pain. Abortive treatment alone is recommended when the attacks occur less than twice a week and are short lived ( Table 19.1 ). Prophylactic therapy is added when the headaches are more frequent or disabling to the patient’s occupation or social activities. Patients with frequent migraine are treated with a combination of preventive and abortive therapies.
|Sumatriptan||4 mg, 6 mg||SQ|
|Sumatriptan||6.5 mg/4 hr||TD|
|Sumatriptan||25 mg, 50 mg, 100 mg||PO|
|Sumatriptan/naproxen||85 mg/500 mg||PO|
|Rizatriptan||5 mg, 10 mg||PO, MLT|
|Zolmitriptan||2.5 mg, 5.0 mg||PO|
|Eletriptan||20 mg, 40 mg||PO|
|Almotriptan||6.25 mg, 12.5 mg||PO|
|NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDs)|
|Naproxen||375 mg, 500 mg||PO|
|Prochlorperazine||2 mg to 10 mg||IV|
|Metoclopramide||10 mg||PO, IV|
|Butalbital, caffeine, and acetaminophen preparation||1–2 pills||PO|
|Isometheptene mucate||1–2 capsules||PO|
Mild to moderate headaches . Many patients find relief with acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), or aspirin and do not seek medical attention. Nonprescription combinations of acetaminophen, aspirin, and caffeine may be quite effective. NSAIDs are beneficial for patients with occasional headaches or for the brief lancinating pain. These pains are ice pick–like (primary stabbing headache) and localize to the scalp, especially the temporal regions.
Alternative abortive therapy in patients with mild to moderate headache include butorphanol nasal spray, an isometheptene–dichloralphenazone–acetaminophen combination, and a butalbital–caffeine–acetaminophen combination. We use the butalbital–caffeine–acetaminophen combination cautiously because of its high abuse potential and its tendency to produce rebound headaches. Butorphanol nasal spray is a mixed opiate agonist–antagonist, dosed as one spray in one nostril, which may be repeated in 1 hour for inadequate pain relief. However, the high abuse potential of butorphanol limits its routine use. Intranasal lidocaine (4% solution, 0.5-ml dose) may abort migraine headaches, although recurrence is a problem with this drug.
When the migraine begins as a mild headache with subsequent progression to a moderate or severe migraine, we recommend early initiation of triptans, which is effective in the early headache stages before cutaneous allodynia ensues.
Moderate to severe headache . For patients with moderate to severe pain, the options for therapy are numerous. Triptans (5HT 1 B/D serotonin agonists) are the most widely used for such patients. The choice of triptan largely depends on the rapidity and the length of the migraine headache and the presence of nausea and vomiting (see Table 19.1 ). If the headache onset is between 15 and 45 minutes and the patient is not severely nauseous or vomiting, one of the faster-onset oral triptans (sumatriptan, zolmitriptan, eletriptan, almotriptan, or rizatriptan) is an excellent option. Rizatriptan (5–10 mg) comes in a wafer form, providing an alternative route of oral administration, even though its absorption is still primarily in the gastrointestinal tract. The wafer contains aspartame, which may limit patients who have their headache triggered by this substance. Rizatriptan interacts with propranolol, requiring the physician to halve the dose of rizatriptan with concurrent use. While all triptans are superior to placebo for pain freedom, analysis of 74 randomized clinical trials suggest that eletriptan and rizatriptan are most likely to lead to the best pain-free response. Sumatriptan together with naproxen is also available in a single tablet. Oral triptans may be taken at the onset of the aura. For unclear reasons, some patients seem to respond better to one triptan than the others, and a trial and error approach may be required.
In individuals with either rapid-onset migraine or severe nausea or vomiting precluding oral intake, subcutaneous (sumatriptan), intranasal (sumatriptan or zolmitriptan), or transdermal (sumatriptan) preparations are alternative routes of triptan administration. Patients should be advised to take the triptan at headache onset. Patients using the nasal form of triptans should be instructed to tilt their head forward during administration to reduce the amount of the drug delivered to the gastrointestinal tract and help eliminate the bitter taste.
Patients with headaches of slower onset (over hours) and longer duration (days) and in whom recurrence is a problem may benefit from triptans with slower onset and longer half-lives (naratriptan or frovatriptan). Since menstrual migraine has these characteristics, these triptans are often used in such patients.
Oral sumatriptan may be less effective in children than in adults; however, studies to date have been relatively small. Intranasal sumatriptan, zolmitriptan, or almotriptan may provide a reasonable option for children or adolescents with acute migraine. Almotriptan has been approved for use in adolescents, and rizatriptan is approved for children 6 years and older.
The amount of triptan that can be used in a 24-hour period is limited. The maximum single dose of oral sumatriptan is 100 mg, and the dosage taken over 24 hours should not exceed 200 mg. Triptan contraindications include coronary artery disease, Prinzmetal’s angina, uncontrolled hypertension, cerebrovascular disease, hemiplegic or basilar migraine, pregnancy, and use of an ergot-containing compound or monoamine oxidase inhibitors within the previous 24 hours. Serious cerebrovascular and cardiovascular side-effects are extremely rare. Both electrocardiography and positron emission tomography perfusion studies suggest that most cases of chest pain associated with the triptans are not cardiac related. Triptans are relatively contraindicated in individuals taking selective serotonin reuptake inhibitors (SSRIs) because of the risk of serotonin syndrome, which is characterized by tachycardia, hypertension, and hyperthermia and is extremely rare in our experience. The main side-effects of the oral triptans are paresthesias, fatigue, and dizziness.
Alternative treatments for moderate to severe migraine include intranasal DHE and dopamine receptor antagonists. Haloperidol, droperidol, prochlorperazine, chlorpromazine, and metoclopramide may be effective in treating acute migraine, particularly in patients with nausea and vomiting. Additionally, monoclonal antibodies targeting the CGRP receptor (CGRP antagonists) have been investigated as a novel acute treatment for migraine. The development of a selective serotonin 5HT1F receptor agonist may also be helpful with less vasoconstrictive properties.
Currently there is no effective treatment for aborting the visual aura of migraine. Observation is usually the safest approach. When migrainous infarction is suspected and evolving, one may try 10 mg of nifedipine sublingually, keeping in mind that hypotension is a possible side-effect. The efficacy of inhaled amyl nitrate and isoproterenol is unproven.
Severe migraine headache in the emergency department . For patients with severe pain and nausea, the following regimens may be tried:
Intramuscular or intravenous ketorolac, 30–60 mg. Prochlorperazine, 10 mg, may be given before ketorolac to lessen nausea.
Intravenous DHE. Prochlorperazine 10 mg is combined with 1 mg of DHE. Half of the solution is given intravenously over 1–2 minutes. If chest pain ensues, the drug is discontinued. If there is no response, the remaining solution is administered in 15–20 minutes. In rare cases of refractory migraine, DHE 0.5–1 mg may be given every 8 hours for 3 days.
Intravenous prochlorperazine, 10 mg. Boluses of 2 mg are given every 5 minutes until the headache abates or a total of 10 mg is given. When administering prochlorperazine, it is important that the patient does not drive home alone because it is sedating. Intravenous hydration is a very effective adjunct, as most patients with severe acute migraine have become dehydrated. Premedication with 1 mg of benztropine mesylate may help eliminate some of the side-effects of this regimen.
Intravenous valproic acid, 10 mg/kg over 60 minutes.
Intravenous methylprednisolone or, in prolonged migraine, dexamethasone.
Preventive therapy is indicated when headaches occur more than once or twice a week or produce significant disability, or when symptomatic therapy fails ( Table 19.2 ). The goal of prophylaxis is to reduce or eliminate the need for acute therapy. Even if preventive therapy is not completely effective, it may render acute therapy more efficacious and lessen the risk of rebound headaches. Triggering factors such as certain foods (chocolate, cheese, nuts) should be eliminated. We try to tailor preventive therapy to meet the individual needs of the patient. For instance, patients who are depressed may fare better with an antidepressant like nortriptyline, while patients with mood swings might benefit from valproic acid. Propranolol may be best for patients with hypertension. Topiramate can be used in individuals desiring weight loss. The medications most frequently used to prevent migraine headaches include (1) beta-blockers, (2) calcium channel blockers, (3) antidepressants, and (4) anticonvulsants.
|Propranolol||60–300 mg LA|
|CALCIUM CHANNEL BLOCKERS|
|Verapamil||120–480 mg SR|
|Valproic acid||500–2000 mg|
|Topiramate||25–300 mg (slow titration)|
|Lamotrigine||50–300 mg (slow titration)|
|Zonisamide||25–300 mg (slow titration)|
|Methysergide||2 mg three times per day|
|Coenzyme Q10||150–300 mg|
|Botulinum toxin||150–200 units|
Beta-blockers . It may take at least a month to assess the efficacy of beta-blockers, which are often used as first-line agents and have an efficacy in the range of 60–80%. Propranolol 60 mg LA (long-acting) is the usual starting dose, and patients are instructed to increase the dose to 120 mg LA after 7 days if the initial 60 mg dose is well tolerated. Thereafter, the dosage can be raised in 60-mg per week increments up to 300 mg a day. Occasionally, patients will not respond to propranolol but will to other beta-blockers such as metoprolol or atenolol. If the patient is headache free for 6–12 months, a taper of the beta-blocker over several weeks can be attempted.
Calcium channel blockers . Calcium channel blockers such as verapamil are also an excellent choice for prophylactic therapy, particularly in patients with migraine with aura and hemiplegic migraine. Their main advantage is their limited side-effects, with constipation, arrhythmias, heart failure, and hypotension being the most common. The initial dose is usually 120 mg SR (sustained release), which can be increased by 120-mg SR increments as necessary. Most patients respond by 360 mg, but occasionally 480 mg a day is necessary. Verapamil works in 60–70% of patients with migraine. It is recommended that patients on verapamil have a baseline electrocardiogram and another check every 6 months. In one study of patients with cluster headache taking verapamil, 18% had a potentially serious cardiac rhythm disturbance. Amlodipine is another good alternative, and doses of 2.5–5.0 mg are usually sufficient.
Antidepressants . Antidepressants are highly effective, particularly when patients have insomnia, depressive symptoms, or a combination of migraine and tension-type headaches. Amitriptyline and nortriptyline seem to be the most effective in this category, although some patients may respond to fluoxetine, nefazodone hydrochloride, sertraline hydrochloride, venlafaxine hydrochloride, duloxetine, and desipramine. Compounds that block norepinephrine uptake seem to be the most effective. Nortriptyline is typically chosen over amitriptyline because the latter has more anticholinergic side-effects. Nortriptyline is started at either 10 or 25 mg depending on the size and age of the patient. The dosage can be increased as necessary, typically each week until a balance between efficacy and side-effects is achieved. Most patients, if they are going to respond to nortriptyline, will do so by the time they reach a dose of 50 mg a day.
Anticonvulsant drugs . The anticonvulsant drugs, particularly the newer ones, have proven to be relatively effective in migraine prevention. Many patients find topiramate extremely effective, although some find the cognitive side-effects intolerable. The initial dose can be 25 mg per day, then the dosage should be gradually increased over weeks (25 mg/week) to reduce the risk of cognitive side-effects, which are more likely to occur with rapid dose escalations and at doses higher than 200 mg/day. Many patients benefit from the associated appetite suppression and weight loss, but untoward side-effects include memory and language difficulty, paresthesias, kidney stones, glaucoma, and myopia. Zonisamide, a related drug, may be used if the side-effects of topiramate are intolerable or if a once a day regimen is desired.
Gabapentin may be effective in the treatment of migraine and chronic daily headache but has had conflicting results in various studies. High doses of gabapentin in the 2400–3600 mg per day range may be necessary to achieve a beneficial effect, but lower doses may also work in some patients. Pregabalin and lamotrigine have also been successful in the treatment of migraines. Older anticonvulsants such as carbamazepine and phenytoin may be used but with variable success.
Valproic acid can be used as a preventive option. The starting dose of 125 mg twice a day is slowly increased to 500–1000 mg per day in divided doses. Patients often do not require large doses for a therapeutic effect. The side-effects, including nausea, alopecia, tremor, and weight gain, along with hepatotoxicity and teratogenicity, usually limit the use of valproate as a preventive therapy. The anticonvulsant drugs may be best utilized in patients with cardiac disease or mood disorders, or in those with exercise intolerance.
CGRP Antagonists . These medications are being investigated and are showing promise as both preventative and abortive therapies for migraine.
Miscellaneous prophylactic medications . Riboflavin in high doses (400 mg per day) may be effective in migraine prevention. Riboflavin may enhance a deficient mitochondrial energy reserve, a potential factor in migraine etiology. Magnesium deficiency in the brain has been suggested as a potential mechanism of migraine. Several trials suggest magnesium supplementation is probably effective. Coenzyme Q10 in doses of 150–300 mg may also be tried. Petasites extract (butterbur) has also been used. Onabotulinumtoxin A for treatment of chronic migraine has been shown to be efficacious in two phase 3, placebo-controlled trials in reducing headache symptoms, decreasing headache-related disability, and improving health-related quality of life. During the double-blind phase of the trials, patients treated with onabotulinumtoxin A had significant improvements compared with placebo in frequency of headache days, headache-related disability, and headache-related quality of life.
Short-term continuous use of oral sumatriptan, frovatriptan, or naratriptan may be effective in preventing menstrual migraine. One regimen used 25 mg of sumatriptan three times per day for a total of 5 days. Transdermal estrogen, continuous contraception (ethinyl estradiol and levonorgestrel), and NSAIDs also may be used as prophylaxis for menstrual-related migraine. Cyproheptadine is frequently used as migraine prophylaxis in children. NSAIDs are beneficial prophylactically for patients with migraine associated with sexual activity (coital headache).
Nontraditional treatments . Relaxation training, biofeedback, and cognitive–behavioral therapy may be helpful for some patients. Although anecdotally acupuncture may be effective, confirming evidence is lacking.
Some studies suggest that percutaneous closure of a patent foramen ovale in patients with migraine reduces their headache frequency ; however, randomized clinical trials have failed to prove this treatment effect.
The use of transmagnetic stimulation and occipital nerve stimulation in migraine treatment has been suggested, but their benefit remains unproven.
Acephalgic Migraine (Typical Aura Without Headache)
Patients with migraine may have transient neurologic events without headache. When such events occur in patients older than 40 years, concern of a possible transient ischemic attack (TIA) is raised. In any age group, seizures may be considered. Fortunately, there are features that help differentiate these disorders. The migraine aura has a characteristic buildup of scintillations. The episodes may occur in a flurry and tend to last longer than a typical TIA. Patients often have a remote history of migraine headaches. Some even have mild accompanying discomfort but do not think it is important to report it. The intensity of their headache is often not as severe as it was previously.
In a younger patient with visual aura without headache, but with a previous history of migraine, further testing may be unnecessary. However, in patients older than 40 years, the new onset of acephalgic migraine is a diagnosis of exclusion. Workup would include neuroimaging to exclude a lesion of the occipital cortex and to check for ischemic changes. Electroencephalography can be performed to rule out an irritative lesion. When the aura is characterized by visual loss, cardiac emboli, carotid insufficiency, and hypercoagulable states should also be considered.
Treatment of acephalgic migraine . If tolerated, 325 mg of aspirin per day may be given, particularly in elderly individuals in whom the diagnosis may be uncertain. It may lessen acephalgic migraine episodes and help prevent stroke in case the events were in fact TIAs. In patients in whom aspirin is ineffective or intolerable, calcium channel blockers (verapamil, 120–360 mg (SR) per day), can be considered for those with recurrent disabling episodes. Often, patients are reassured knowing that their visual episodes are migrainous and benign and decline pharmacologic treatment.
Other Headache Types
Chronic Daily Headache
Chronic daily headache is a category of headaches including chronic migraine (described already), chronic tension-type headaches, hemicrania continua, new daily persistent headache, and posttraumatic headaches. Affected patients have headaches for 15 or more days per month, and the majority have an element of medication-overuse headache.
Tension headaches are probably a continuum of migraine headaches. The pain is mild to moderate in intensity and is often described as pressure or tightness. There is no aura, nausea, or vomiting, and the headaches are usually not aggravated by exercise (see Box 19.3 ). Photophobia and phonophobia are rarely present, and the headache location is often bilateral, over the eyes, temples, occipital region, or on top of the head. Patients often have tender spots over the shoulder girdle muscles. Most tension headaches are episodic; however, some patients have chronic tension-type headaches without pain-free intervals.
Many patients with chronic daily tension headaches have a history of migraine, and migraines may periodically occur. Many of these patients have concurrent depression. In patients with tension headache, one should be aware of the possibility of secondary headache disorders or rebound headaches from analgesic overuse (see Medication-Overuse Headache ).
Treatment . Such patients with tension headaches pose a therapeutic challenge. The abortive and prophylactic medications used in migraineurs may be tried. Nortriptyline and amitriptyline may be the first-line agents for these patients, and topiramate may be effective. Patients with tension headaches should be assessed for temporomandibular joint dysfunction or sinus disease before starting preventive therapy. Some patients with tension headache do not respond to medication and may benefit from other therapies, including stretching exercises and acupuncture. Botulinum toxin injected into the frontal and occipital muscles may be used in refractory tension headache, but studies have not demonstrated fewer headaches in this subset of patients.
Medication-overuse headaches share similar clinical characteristics with tension headaches. Although rebound headache is classically associated with overuse of narcotics (taken 10 days a month or more) or over-the-counter analgesics (taken 15 days a month or more), this phenomenon also may be observed with triptan and ergot overuse.
Treatment . It is important to taper the overused medication, exercising caution with quick discontinuation of certain responsible medications (barbiturates, benzodiazepines, opioids, or caffeine-containing compounds) because of the potential for life-threatening complications. If not already a contributing factor, NSAIDs or a short course of corticosteroids may help the patient’s symptoms. During the taper, adding botulinum toxin may be effective in patients with acute medication-overuse headache and baseline chronic migraine. If outpatient detoxification fails, inpatient management may be necessary. Intravenous DHE, 1 mg, combined with 10 mg of intravenous metoclopramide every 8 hours for 3–5 days is one effective regimen to treat analgesic overuse.
Cluster headache is a severe unilateral headache disorder that predominantly occurs in men (see Box 19.4 ). These headaches occur in clusters or on a daily basis for weeks to months. Although most cluster headaches are episodic, rarely they are chronic and without remission. Cluster headaches are often severe, awakening a patient from sleep. They localize over the periorbital region and are often associated with rhinorrhea and tearing. Alcohol is a common trigger. The attacks are much shorter than migraine, lasting 0.5–3 hours. There is often no nausea or vomiting; aura is rare but can occur. Many patients develop signs of a Horner syndrome. Occasionally, only ptosis or miosis is present. After several attacks, a permanent Horner syndrome may ensue. Contrasting the migraine patient who desires sleep, a cluster headache patient cannot stay still. The headache is so severe that some patients literally run around the room screaming, and some patients even contemplate suicide. Interictally, some patients will suffer typical migraine headaches.
The major entity to exclude in a patient with a painful Horner syndrome is a carotid dissection (see Chapter 13 ). Other entities that may mimic cluster headaches include arteriovenous malformation, brainstem compression by tumor, vertebral artery aneurysm, cavernous carotid artery aneurysms, sinusitis, temporal arteritis, Tolosa–Hunt syndrome, orbital myositis, and pituitary tumors. In patients presenting with a painful Horner syndrome, MRI of the neck, including axial T1-weighted images and angiographic sequences, is recommended to exclude carotid dissection.
Treatment . The treatment of acute cluster attack may be difficult. Emergently, the following regimens may be tried:
100% oxygen therapy via a face mask at 12–15 L/min for 15–20 minutes
Subcutaneous sumatriptan or intranasal sumatriptan or zolmitriptan
Intranasal or intravenous DHE
Intranasal lidocaine 4%
Corticosteroids (2-week prednisone taper)
Corticosteroids often take hours to begin to work. However, they may be useful in transition to other preventive therapies. Verapamil is considered first-line prophylactic treatment in prolonged episodes or chronic cluster headache and is comparable to lithium. Other options include twice-daily ergotamine therapy. Indomethacin may benefit certain patients, and valproic acid may provide effective prophylaxis. The newer anticonvulsants including gabapentin, pregabalin, topiramate, and lamotrigine may be tried.
When patients are refractory to monotherapy, combination therapy may be necessary. Verapamil and lithium are usually tried together first. Valproate and verapamil is another effective combination.
Rarely, patients may require intravenous DHE every 8 hours to break the cluster. When all medications fail and headaches are strictly unilateral, radiofrequency thermocoagulation of the Gasserian ganglion or trigeminal nerve section may be tried. However, the resultant corneal and trigeminal anesthesia may lead to complications, and the procedures are not always effective. Intractable cluster headaches have also been treated by deep hypothalamic, occipital nerve, or sphenopalatine ganglion stimulation.
Paroxysmal Hemicrania and Hemicrania Continua
Paroxysmal hemicrania refers to a headache syndrome characterized by brief episodes of unilateral pain localizing over the orbital and temporal regions lasting 2–45 minutes. Patients experience multiple attacks a day, and some have 40–50 attacks in a 24-hour period. The pain is associated with autonomic dysfunction such as conjunctival injection, lacrimation, nasal congestion, ptosis, and eyelid edema. While there are many similarities between paroxysmal hemicrania and cluster headache, paroxysmal hemicrania is distinguished by its shorter duration and exquisite response to indomethacin. It has been described as a disorder in women, but other studies did not demonstrate a female preponderance. Although indomethacin is the treatment of choice, other patients may respond to topiramate, verapamil, acetazolamide, or other NSAIDs. Some patients will have superimposed mild and dull hemicranial discomfort between episodes.
Headaches which are similar in quality but continuous are termed hemicrania continua and are also responsive to indomethacin.
The acronym for this syndrome stands for “ s hort-lasting, u nilateral, n euralgiform headache with c onjunctival injection, and t earing.” Patients may experience hundreds of attacks a day lasting 5–240 seconds. This rare condition is similar to the paroxysmal hemicranias but is distinguished by less severe pain, more marked autonomic activation, and unresponsiveness to indomethacin. Lamotrigine is the most effective treatment in nearly two-thirds of patients, but gabapentin, topiramate, and zonisamide can also be used prophylactically. Like cluster headaches, SUNCT syndrome may be mimicked by pituitary tumors and posterior fossa lesions.
Ice Pick Headache (Primary Stabbing Headache)
Some patients experience sudden stabbing pain that may be described as like being stabbed with an ice pick. The pain is often located in the temple region, but the occipital area may also be involved. The pain often lasts seconds but may persist for minutes. Many patients have underlying migraine or tension headaches. The pain may occur several times a day and may awaken a sleeping patient. Occasionally, the examiner can palpate the area and elicit the pain. The pain of a corneal erosion may be brief and present upon awakening and should be carefully considered in a patient with stabbing periorbital pain. Patients respond best to indomethacin or other NSAIDs.
Patients with cough headache may be divided into two broad groups. First, cough-induced headaches may be associated with an intracranial lesion, particularly a posterior fossa lesion. Arnold–Chiari tumors and subdural hematomas are other causes. Given this differential diagnosis, neuroimaging is always indicated with this type of headache.
Patients in the second group with cough-induced headache have no detectable intracranial lesions despite extensive investigation. These patients often respond to a course of indomethacin or other NSAID.
Thunderclap Headache and the Reversible Cerebral Vasoconstriction Syndrome
Thunderclap headache. This term is used to describe a sudden and severe headache. Although controversy exists regarding the significance of such a headache, we believe an intracerebral hemorrhage or an unruptured aneurysm has to be strongly considered. Raps et al. concluded that thunderclap headache may be induced by a variety of mechanisms, including thrombosis or expansion of an aneurysm or intramural hemorrhage. Some patients with thunderclap headache have no identifiable cause. Patients with thunderclap headache should be evaluated with emergent computed tomography (CT) and lumbar puncture. If both are negative, and the suspicion remains high for an unruptured aneurysm, CT or MRA should be performed.
Reversible cerebral vasoconstriction syndrome . One of the most common causes of thunderclap headache with associated diffuse, segmental reversible cerebral vasospasm is referred to as reversible cerebral vasoconstriction syndrome (RCVS). It can spontaneously occur and resolve within 1–3 months. Risk factors of RCVS include being postpartum or having a history of migraine. Vasoactive substances that can induce RCVS include cannabis, cocaine, amphetamines, ecstasy, ergotamine, triptans, nasal decongestants, and SSRIs. Combining binge drinking and the use of vasoactive substances (particularly cannabis) is a significant risk factor. Patients present with recurrent thunderclap headaches, normal or near-normal cerebrospinal fluid, and reversible vasospasm of cerebral arteries noted on conventional cerebral angiography, CT, or MRA. Patients may have the headache alone or in combination with neurologic symptoms including deficits in mental status, motor examination, sensation, speech, ataxia, and seizures. Visual symptoms of blurred vision, vision loss, visual field defect, and retroorbital eye pain have been described. The main complications of RCVS are ischemic or hemorrhagic stroke (7%; see Chapter 8 ) and subarachnoid hemorrhage (22%). The utility of treating RCVS with calcium channel blockers is inconclusive. Even without treatment, patients typically have complete or near resolution of vasospasm within 3 weeks of RCVS onset.
Greater Occipital Neuralgia
Some patients experience episodic pain in the back of head at the exit site of the greater occipital nerve. The pain often ascends ipsilaterally along the nerve’s distribution behind the ear then occasionally forward toward the eye. The discomfort usually lasts seconds but may recur frequently during the day. The patient typically has pain and tenderness at the point where the greater occipital nerve pierces the tendinous insertion of the splenius capitis muscle at the skull base. Many patients have superimposed tension and migraine headaches.
Treatment with local injection of lidocaine has a high success rate. Occasionally repeated injections are necessary to break the cycle. If patients do not respond to local lidocaine injection, NSAIDs, carbamazepine, gabapentin, a soft cervical collar at night, or a short course of corticosteroids may be tried. Refractory cases may be treated with occipital nerve stimulation and very rarely surgical decompression or radiofrequency ablation.
Elderly patients may experience headaches shortly after falling asleep. The headache is throbbing and global in location, is short lived, and usually resolves within an hour. This disorder is also recognized in young patients and may be unilateral. Caffeine at bedtime is usually the first-line treatment of these headaches. Lithium may also prevent the headaches, but its side-effects in the elderly population may limit its use.
Patients with acute carotid dissection may develop throbbing pain over the periorbital area. Many patients will have accompanying neurologic signs such as a Horner syndrome or contralateral weakness or numbness. A patient with an isolated painful Horner syndrome should be considered to have a carotid dissection until proven otherwise. Other clinical manifestations, radiographic features, and management of this condition are discussed in detail in Chapter 13 .
The headache of temporal arteritis is often described as an ache concentrated over the temporal arteries. The pain rarely can be severe and the area exquisitely sensitive to touch. Although the pain is often concentrated over the temporal region, it may occur over any portion of the head. The pain typically abates within days of starting corticosteroids. This condition, particularly with regard to visual loss, pathophysiology, and management, is reviewed in Chapter 5 .
Mild to moderate headaches are common after head injury. Patients may or may not have experienced a loss of consciousness. Typically, the headache is one of many symptoms that accompany the posttraumatic syndrome. Vertigo, irritability, concentration difficulty, and short-term memory loss are other frequent complaints. The posttraumatic headache may simulate tension headaches or migraine headaches and may improve spontaneously or persist indefinitely. The IHS criteria require the onset of the headache to be within 7 days after the injury or upon return of consciousness. Migraine, common daily headache, and cluster may follow mild head trauma. Posttraumatic headaches may last for several years, regardless of financial compensation issues. If tolerated, antidepressant compounds may reduce some of the symptoms. Other prophylactic headache medications such as propranolol, verapamil, topiramate, and valproic acid may also be tried with variable success.
Patients with glossopharyngeal neuralgia experience pain in the pharynx and base of the tongue. The pain may be triggered by swallowing, coughing, or talking. and the pain is usually sharp, stabbing, or lancinating. The condition is usually idiopathic, but mass lesions should be carefully considered. As in patients with trigeminal neuralgia, most cases result from compression by a dolichoectatic artery or venous structure. Treatment of glossopharyngeal neuralgia includes anticonvulsants, antidepressants, and baclofen therapy. If medical therapy fails, the glossopharyngeal nerve may be thermocoagulated. Other patients may benefit from microvascular decompression.
Headache is a prominent symptom of patients suffering from intracranial hypotension, also termed CSF hypovolemia syndrome . Patients may have associated nausea, vomiting, tinnitus, and photophobia. The hallmark feature of this disorder is pain aggravated by an upright posture, but the rare patient may paradoxically have a headache when lying down. Some patients will develop unilateral or bilateral sixth nerve palsies resulting from the traction on these nerves as the brain sinks downward from the intracranial hypotension. Rarely, patients may complain of transient visual obscurations or blurred vision, and binasal field defects have been documented. Rare complications include nystagmus from eighth nerve dysfunction and enophthalmos. The downward displacement of the brain is seen on sagittal MRI, and diffuse meningeal enhancement is often present ( Fig. 19.3A,B ). If severe, bilateral subdural hematomas or organized hygromas ( Fig. 19.3C ) may develop.