Symptoms and Diagnosis of Migraine

Migraine is classified into two main forms: migraine with aura (formerly referred to as “classic migraine”) and migraine without aura (formerly referred to as “common migraine”), based on criteria of the International Headache Society (IHS).³¹ Other varieties of migraine include ophthalmoplegic, retinal, basilar, and familial hemiplegic. Complications of migraine include migrainous infarction (a neurologic deficit not reversible by 7 days) and status migrainosus (an attack of headache or aura lasting more than 72 hours). Migraine aura can exist without headache, and the same patient may, at different times, experience headache with aura, headache without aura, or aura without headache.^32,33

To diagnose migraine without aura, five attacks are needed, each lasting 4 to 72 hours and having two of the following four characteristics: unilateral location, pulsating quality, moderate or severe intensity, and aggravation by routine physical activity. In addition, the attacks must have at least one of the following: nausea or vomiting or photophobia and phonophobia. Migraine without aura is more common than migraine with aura and is usually more disabling.

Migraine with aura is diagnosed when there have been at least two attacks with any three of the following features:

A simpler working definition for the clinical diagnosis of migraine was proposed by Solomon and Lipton.³⁴ A positive diagnosis could be made on any two of the following four symptoms:

A similar headache must have occurred in the past, and structural disease must have been excluded. Migraine attacks generally are divided into five phases: the prodrome (hours or days before the headache), the aura (migraine with aura), the headache, the headache termination, and the postdrome phase.³² Symptoms of the prodrome may include mental, neurologic, or general (constitutional, autonomic) symptoms. Individuals may experience depression, euphoria, irritability, restlessness, mental slowness, hyperactivity, and drowsiness. General symptoms may include a feeling of coldness, sluggishness, thirst, anorexia, diarrhea, constipation, fluid retention, and food cravings. Photophobia and phonophobia may also occur.

The aura is a group of neurologic symptoms that precede or accompany the attack. They may be visual, sensory, or motor and may also cause language or brainstem disturbance. Headache usually occurs within 60 minutes of the end of the aura,³¹ but it may begin with the aura. Most patients have more than one type of aura and progress from one type to another in subsequent attacks. Common visual symptoms are the positive phenomena, such as hemianopic photopsia (flashes of light) and teichopsia or fortification spectra. Scotomata may follow. Complex visual distortions and hallucinations are reported but are more common in younger people.³⁵ Somatosensory phenomena, typically paresthesias with anatomic march of symptoms, may occur, and motor disturbance may result in hemiparesis. Aphasia has also been reported.^8,36 Migraine aura symptoms may therefore be characterized by both positive and negative symptoms. Acephalgic migraine is an entity characterized by the neurologic dysfunction of the aura but without headache. This is strictly a diagnosis of exclusion, especially in older people. These so-called migraine accompaniments may occur for the first time in the older age group^37,38 and can be easily confused with transient ischemic attacks (TIAs) except in the most classic of cases. Migraine with aura and acephalgic migraine can be confused with TIAs, and vice versa. Headache occurred with 36% of TIAs in one series³⁹ and is more common in vertebrobasilar ischemia.^40,41 Migrainous aura in older adults presents a particularly difficult diagnostic dilemma. Transient hemiparetic or hemisensory symptoms occurring in older people for the first time should be assumed to be vascular (i.e., TIA) in cause until proven otherwise. Alternating hemisensory/paretic symptoms are more likely to be migrainous but still could have an embolic cause. Investigation including carotid Doppler studies and echocardiography will be necessary to manage potentially treatable embolic sources. Visual disturbance is more likely to be helpful as fortification spectra and colored zigzag lines are unlikely to occur in straightforward TIAs and are almost always migrainous in origin. Migraine with aura may occur for the first time in older adults, although, in general, new-onset migraine in the older age group is unusual^13,42 and may reflect the development of vascular change. It is often helpful in these cases to elicit a previous history of common migraine earlier in life.

The headache of migraine is typically throbbing in nature and exacerbated by exercise.⁴³ The pain may be unilateral in 60% of cases but bilateral at the outset in up to 40%.⁸ Unilateral headache may later become bilateral during the attack. The intensity is moderate to severe, and pain may radiate down the neck to the shoulder. Some 40% of migraineurs report short-lived jabs of pain lasting seconds and having a needle-like quality, the so-called ice pick pains.⁴⁴

The common accompanying symptoms of nausea and vomiting may make it difficult for the patient to take oral medication. Photophobia and phonophobia are common; many patients retire to a dark and quiet room for rest. Constitutional, mood, and mental changes are universal,⁸ and patients are usually left feeling lethargic for a period after the attack.

Basilar migraine is a variant characterized by brainstem dysfunction such as ataxia, dysarthria, diplopia, vertigo, nausea and vomiting, and alteration in cognition and consciousness. Headache is invariable. In older adults these symptoms should be assumed to be of vascular origin until proven otherwise.

Ophthalmoplegic migraine is rare and can be confused with the presentation of berry aneurysm. Attacks of migraine-like pain occur around the eye with oculomotor nerve dysfunction and dilation of the pupil. The ophthalmoplegia may last from hours to months. The differential diagnosis includes orbital inflammatory disease and diabetic mononeuropathy.

Migraine attacks may vary in frequency from a few each year to several each week. Trigger factors include certain foods, red wine,⁴⁵ hormone replacement treatment in postmenopausal women,⁴⁶ irregular meals, and a change in sleep habit.⁴⁷ Environmental triggers include flickering lights, noise, rapidly altering visual stimuli, and even certain types of weather. Head injury and stress may lead to migraine attacks.

Treatment of Migraine

Once the diagnosis has been established, reassuring the patient may suffice. Any obvious precipitating cause such as diet, lack of sleep, or environmental factors should be discussed. Relaxation therapy may be helpful, but special diets have little place in management.

Pharmacotherapy includes treatment of the acute attack and consideration of prophylactic therapy. It should be remembered that changing biology in older adults will influence response to medication.⁴⁸ Gastric emptying slows, delaying absorption of medication; hepatic blood flow is reduced and so is glomerular filtration rate, affecting drug metabolism, usually leading to increased half-life. In general, therefore, pharmacotherapy should be started with caution in older adults, who are often taking medications for other comorbidities. Acute treatment should be started by the patient at the outset of an attack and is best limited to simple soluble analgesics such as paracetamol or aspirin (Table 59-1). Combination analgesics such as co-proxamol should be avoided, if possible, because of side effects and risk of medication overuse leading to so-called transformed migraine. For a more severe headache, nonsteroidal antiinflammatory drugs (NSAIDs) are used.⁴⁹ Ibuprofen (200 mg tid) may be obtained in the United Kingdom without prescription, or naproxen (250 mg tid) by prescription, or diclofenac (75 mg bid). This group of drugs should be administered with caution in the older adult population because of the increased risk of gastrointestinal hemorrhage, especially when there is a past history of peptic ulceration^50,51 or renal insufficiency.

For moderate to severe migraine not responding to simple analgesia, sumatriptan can be tried. The initial dose is 50 mg orally and can be increased to 100 mg if there is no response. Subcutaneous self-administration is the preferred route when there is significant nausea or vomiting. Sumatriptan is a 5HT₁ agonist and is thought to act as a selective cerebral vasoconstrictor. Up to 80% of patients obtain relief from headache within 2 hours after an injection⁵² and up to 65% after a tablet dose.⁵³ The advantage is that the drug may be administered at any point during an attack and repeated if necessary. Flushing, tingling in the neck and head, and chest tightness can occur in up to 5% of patients.⁵⁴ Because sumatriptan may cause coronary vasoconstriction, it is contraindicated in patients with ischemic heart disease or uncontrolled hypertension. Special care in some older people is required because the loss of subcutaneous fat may lead to intramuscular injection and more rapid absorption. A recent study failed to demonstrate increased risk of stroke, myocardial infarction, cardiovascular death, ischemic heart disease, or overall mortality in older adults.⁵⁵ Pharmacotherapy should be combined with rest and sleep. A number of newer triptans have been licensed for use in migraine treatment and may be selected depending on the individual patient.⁵⁶

Ergotamine preparations are best reserved for occasional (>1 month interval) severe headaches. They are potent vasoconstrictors and are best avoided in patients with a history of vasoocclusive disease, peripheral vascular disease, or hypertension, and those receiving β-blockers or with a history of Raynaud phenomenon. Patients should be strongly encouraged to avoid overuse of these drugs, because this can lead to resistant medication-misuse headache. Admission for drug withdrawal may be required when this occurs.

The accompanying symptoms of nausea and vomiting are often as disabling as the headache and require treatment in their own right. Metoclopramide is the most commonly used antiemetic, and by promoting gastric emptying, it aids absorption of coadministered medication. However, it can cause extrapyramidal side effects, especially in older people. Domperidone is less likely to cause this problem, as it does not cross the blood-brain barrier, but it does not aid gastric emptying.

Prophylactic therapy is indicated when there is severe recurrent headache causing disruption to daily life—as a guide, more than two severe headaches per month. Various drugs are used, including β-blockers, antidepressants, serotonin antagonists, calcium channel blockers, and, on occasion, anticonvulsants. Treatment is started at a low dose and built to maintenance. Possible side effects should be discussed and the regimen kept as simple as possible because many patients in this age group are likely to have coexistent medication. Patients should be weaned from therapy every 4 to 6 months.

Of the β-blockers, propranolol, metoprolol, and atenolol have all been shown to be effective in up to 60% to 80% of patients, producing a greater than 50% reduction in attack frequency.^57,58 Atenolol (50 to 100 mg daily) has a better side effect profile than propranolol (20 to 160 mg daily). Patients may complain of fatigue, dizziness, nightmares, and cold extremities. Care should be taken when there is peripheral vascular disease and in combination with ergotamine.

The tricyclic antidepressants have been used in migraine prophylaxis, although the evidence for their efficacy is largely based on anecdotal reports or uncontrolled trials. Their effect in headache may be independent of their antidepressant effect.^57,59 Amitriptyline is most commonly used, although fluoxetine has fewer anticholinergic side effects and causes less weight gain.⁶⁰ Paroxetine may be a suitable alternative when anxiety is a factor.⁶¹ Because of their common side effect of drowsiness, the tricyclics are administered at the lowest effective dose at bedtime and slowly increased as necessary. Older people are more vulnerable to the muscarinic side effects. The typical starting dose for amitriptyline should be 10 mg, increasing to 150 mg if needed.⁶²

Sodium valproate (0.6 to 2.5 g daily) is well tolerated, and there is clinical trial evidence of efficacy.⁶³ Side effects of valproate include tremor, ataxia, and, less commonly, an extrapyramidal syndrome. Topiramate now has a license for use in migraine prophylaxis; the use of anticonvulsants for migraine prophylaxis has been reviewed.⁶⁴

Calcium channel antagonists are not licensed for migraine prophylaxis in the United Kingdom but have been shown to be of benefit.⁵⁷ The mechanism of action of these compounds in migraine is uncertain and side effects are common, including edema, flushing, dizziness, and, not infrequently, an initial increase in headache frequency. Improvement of headache may require several weeks of treatment.⁶⁵

Of the serotonin antagonists, the two most commonly prescribed are pizotifen and methysergide. Pizotifen is a 5HT₂ antagonist that is usually commenced in a dose of 0.5 mg at night and increased in stepwise manner to a dose of 4.5 mg. It has mild antidepressant activity but unfortunately stimulates appetite and leads to weight gain if diet is not controlled. It can produce beneficial effects in 40% to 79% of patients.⁶⁶ Methysergide is also a 5HT₂ antagonist with some affinity for the 5HT₁ receptor. It is effective prophylaxis in up to 60% of migraineurs, possibly with better results in those with migraine with aura.⁶⁷ Side effects are common and include myalgia, weight gain, nausea, and hallucinations (especially after the first dose). The complication of retroperitoneal, endocardial, and pulmonary fibrosis is rare and prevented by stopping treatment for 3 to 4 weeks every 4 to 6 months. The starting dose is 1 mg at night but may be increased to 6 mg daily in divided dosage.

Feverfew (Tanacetum parthenium) is an herbal remedy long used for headache treatment. It has limited effect, and the side effects include mouth ulceration and loss of taste.^68,69

Newer treatments for migraine include the approval of onabotulinumtoxin type A for the prophylaxis of chronic migraine. This drug was approved after the PREEMPT clinical trials⁷⁰ and, to date, the safety data are encouraging.⁷¹ Patients should be selected carefully and published injection protocols adhered to.

Tension Headache

Tension-type headache may be broadly classified into infrequent episodic tension-type headache, frequent episodic tension-type headache (at least 10 episodes occurring over 1 to 15 days a month), and chronic tension-type headache (headache occurring on more than 15 days per month).³¹ The clinical features include the following:

In both types of headache, there may be pericranial muscle tenderness with or without increased electromyographic activity, although this does not assume that muscle tension is the cause of the headache.⁷² In all age groups, tension-type headache is the most common form of headache, peaking in the 30s and 40s.⁷³ Chronic tension-type headache is more common in the older age groups than is episodic tension-type headache, and only 5% of patients with chronic tension-type headache report onset after the age of 60 years.⁷⁴ Within all age groups, tension headache remains most common in females with a 1-year period prevalence of 27.1% in females and 25.6% in males in one large telephone-based study.^27,73

The pain of tension-type headache is usually described as a constant ache, which is infrequently pulsatile. Patients may describe a tight band about the head or a sensation of wearing a tight cap. There may be associated stiffness of the neck and upper back; in contrast to migraine, the pain is usually of lesser intensity. Scalp tenderness may lead to avoidance of hair brushing. This symptom is also recorded in migraineurs, and it may persist for some days after the headache has subsided.⁷⁵

The headache may be unilateral or bilateral, commonly occipital or frontal but may involve any site. It can be relieved by changing position.

Patients with episodic tension headache may experience pericranial muscle tenderness with palpable nodules.⁷⁶ Depression, anxiety, and other psychological factors are important in the pathogenesis of tension headache, although, not infrequently, patients may initially deny any role.

Depression is common in the community at large, and in an average family practice in the United Kingdom it is the fourth most commonly diagnosed disorder.⁷⁷ The headache associated with depression can have features described for tension-type headache, and the headaches are often present for years or even throughout the patient’s life. The headache is typically diurnal, usually worse in the morning and in the evening. There may be identifiable emotional, physical, and psychic complaints. These problems merit attention in their own right, especially in older adults when organic pathology is more likely anyway. The presence of severe depression in older people can be easily overlooked. Other headaches associated with depression can be described more bizarrely, with almost a delusional tone. Such headaches may indicate a serious psychiatric disorder and should lead to urgent psychiatric referral.

Treatment includes reassurance, simple analgesia as abortive treatment for the acute attack, and treatment of any psychopathology that may be present. Simple analgesia such as paracetamol should be used for acute attacks of pain. NSAIDs are more likely to be associated with side effects in older adults, such as gastric erosions and renal and hepatic complications.⁷⁸ Frequent episodic tension-type headache and chronic tension-type headache may require the use of prophylaxis—tricyclics such as amitriptyline remain the most useful drugs, especially when there is sleep disorder. The latter is especially useful when sleep disturbance is a prominent symptom.⁷⁹ Fluoxetine (20 mg daily) is less sedating. Paroxetine (10 mg daily) may be helpful when there are additional anxiety symptoms. Monoamine oxidase inhibitors should be avoided if possible. Psychiatric help may be appropriate, although patients often initially reject this suggestion. Relaxation therapy and biofeedback may also have a role.

The mixed headache syndrome—migraine and tension-type headache in the same patient—usually responds to treatment with tricyclic antidepressants with the addition of analgesia for acute episodes. There are no specific data on the prognosis of tension-type headache in older people, although there is a tendency for improvement with increasing age.⁸⁰ It is important to continually bear in mind that secondary headache is more common in older patients and that careful evaluation of the history and examination and a lower threshold for investigation should be applied in older adults with apparent nonspecific headache.

Chronic Daily Headache

The syndrome of chronic daily headache (CDH) accounts for 40% of patients seen in headache clinics⁸¹ and worldwide is estimated to affect 3% to 5% of the population.⁸² Only 5% reported their chronic headache as starting after 60 years of age.⁷⁴ CDH is defined as 15 or more headache days a month for 3 months or more.

There are several subtypes of CDH (Box 59-1), with chronic migraine presenting five times more commonly than chronic tension-type headache to the specialist headache clinic.⁸³ The features of tension-type headache are discussed elsewhere in this section. Medication overuse is probably the third most common form of chronic headache after chronic tension-type headache and chronic migraine and is thought to affect up to 1% of the world population.^84,85 The free availability of analgesics containing caffeine, codeine, barbiturates, and tranquilizers over the counter has been implicated as one cause of this syndrome.^86,87 The management of this syndrome can be particularly challenging and hinges on the discontinuation of analgesic overuse, the possibility of going “cold turkey,” and the use of suitable alternatives for weaning and prophylaxis.⁸⁸ In a proportion of patients the headache may revert to its original episodic form, but in the remainder the avoidance of analgesic overuse will require the initiation of prophylaxis.⁸⁹ Suitable prophylactic treatment such as amitriptyline in an initial dose of 10 mg at night increased to 75 mg as tolerated is effective, with improvement seen at 2 to 14 days. The drug should be continued at an effective dose for 6 months and then withdrawn slowly over 3 months. Caution should be exercised in those with glaucoma and prostatism. Anticonvulsant drugs used in migraine prophylaxis may be effective, and sodium valproate, gabapentin, and, more recently, topiramate have been used with favorable results.^90,91 Patient and physician education is especially important in prevention and management of this difficult headache syndrome.

Episodic migraine may evolve into CDH. In one study, 489 of 630 patients (78%) with CDH had a clear preceding history of episodic migraine.⁹² This so-called transformed migraine may be caused by excessive use of opioid and simple analgesics, barbiturates, ergot compounds, caffeine, and frequent use of triptans. Headaches are often more severe on waking owing to a drug-free withdrawal period overnight effectively causing rebound. Hemicrania continua is side-locked headache that often has autonomic symptoms and shows an exquisite response to indomethacin.^93,94

The differential diagnosis includes headaches arising from the neck, temporal arteritis, mass lesions, and visual acuity problems. Because tension-type headache is often associated with depression, sleep disorder, and situational life events, especially in the older adult population, the treatment of CDH must include behavioral, psychological, and social aspects.

Cluster Headache

This condition, although most common in young adults, may have its onset in the seventh decade when the clinical features are the same.^95,96 The IHS classification divides the condition into episodic and chronic cluster headache, the latter being more common in the older adult population.⁹⁷ A review of the literature suggests a lifetime prevalence of 124/100,000,⁹⁸ with a higher male preponderance in the young but more females older than 60 years affected than males.⁹⁹

Cluster headache is characterized by bouts of severe pain and autonomic activation. The pain is constant, often described as “boring” in nature, and patients are restless in contrast to those with migraine who lie quietly. The pain is often centered around one eye, and there may be ipsilateral lacrimation, nasal congestion, and rhinorrhea. There is usually conjunctival injection, and there may be associated ptosis, meiosis, and eyelid edema. The pain may spread to the whole side of the face. Bouts of pain occur one to three times per day with alarm-clock regularity, commonly an hour or so after going to sleep, and last from 15 minutes to a few hours (with a usual duration of 45 to 90 minutes). The headache may start and end abruptly, and in some patients there may be interictal discomfort.¹⁰⁰ The cluster period typically lasts for 1 to 2 months and then subsides. During the cluster attacks, alcohol is a potent precipitant, usually setting off an attack within an hour of ingestion, as are vasodilator drugs such as nitrates. One study examined the association of alcohol dehydrogenase genotypes and cluster headache but with only preliminary findings.¹⁰¹ The chronic form continues without remission often for many years.

Treatment is symptomatic. Oxygen at 100% is useful in the emergency department and can be given at home. It is important that a high flow valve is used with a nonrebreather mask capable of delivering 7 to 10 L/min. More practically, sumatriptan by subcutaneous injection is the drug of choice for acute attacks.¹⁰² However, it should be remembered that many patients may have cardiovascular disease, which limits the use of this drug. Nasal sumatriptan may be used but appears to be less effective.¹⁰³ Preventive treatments may be considered in terms of short-term measures and longer duration treatment for those with a more chronic course to their clusters. Steroids (e.g., prednisolone 1 mg/kg daily for a week and reducing by 10 mg a week) may shorten a cluster period, but relapse often occurs and so they may be used with other forms of prophylaxis.¹⁰⁴ Verapamil is the drug of choice for all forms of cluster headache prophylaxis¹⁰⁵ and compares favorably with lithium,¹⁰⁶ particularly in view of the plethora of potential neuropsychiatric side effects of the latter. Doses of verapamil range from 240 mg to 960 mg bid in divided dose. Because this drug can cause heart block, a baseline electrocardiogram (ECG) should be taken, an initial dose of 80 mg tid commenced, and then every 10 days or so the dose should be increased in 80-mg increments until attacks are suppressed or side effects prevent further titration. An ECG should be done after each increment. Sodium valproate may be tried in resistant cases.¹⁰⁷ Lithium carbonate given in standard psychiatric doses (600 to 1200 mg) and monitored accordingly is useful in chronic cluster headache but less so in episodic cluster headache. One small trial demonstrated benefit of melatonin 10 mg for prophylaxis.¹⁰⁸ In rare cases, surgical intervention is attempted. Percutaneous radiofrequency trigeminal gangliorhizolysis and posterior fossa trigeminal sensory rhizolysis have been performed but are of unproven benefit. Surgery can cause a reduction in facial sensation and corneal hypoesthesia with increased risk of corneal ulceration.¹⁰⁹

Cluster headache is an underdiagnosed cause of recurrent paroxysmal cranial pain in the older adult population. It may not have the usual classic features in this age group. Treatment may need to be given empirically when there is doubt. Furthermore, symptomatic cluster-like headache may accompany other conditions such as glaucoma and sinusitis.

Chronic paroxysmal hemicrania (Sjaastad headache), a rare variant of cluster headache, differs in the brevity (3 to 45 minutes) and frequency (up to 40 times a day) of the attacks. The invariable response to indomethacin forms part of the diagnostic criteria.²

Cause

Proximal nerve root demyelination due to mechanical irritation of proximal trigeminal nerve root is believed to be the pathophysiology of this condition. The proximal nerve roots lie within central nervous system (CNS) nerve tissue, which extends several millimeters from the surface of the pons. Animal laboratory data, however, are more consistent with a central mechanism mediated by the loss of segmental inhibition within the spinal trigeminal sensory nucleus. To reconcile these observations, Fromm and associates¹¹⁷ proposed that spontaneous peripheral activity from the irritated nerve, in the presence of the failure of the normal central inhibitory mechanisms, may cause paroxysmal bursts of neuronal activity within the trigeminal nucleus and its thalamic relays, perceived as neuralgia by the patient. This has been likened to a form of “sensory reflex epilepsy.”¹¹⁸ Some evidence for the peripheral component of this hypothesis comes from the common finding of vascular loops (arterial or venous) in association with the nerve root in a majority of symptomatic patients.^119,120 Other compressive pathology should be considered, including schwannoma, lymphoma, meningioma, and a variety of other tumors and infiltrative lesions. Pathologic specimens reveal focal demyelination within the proximal (CNS) part of the root. It is proposed that ephaptic transmission of spontaneously generated ectopic impulses results in symptoms.¹²¹ Because vessels tend to become more ectatic with age, this may explain why the condition is more common in older people.

Treatment

The treatment of this condition is initially medical.^122–124 Occasionally the symptoms are so severe that hospital admission is required to control symptoms and prevent a downward spiral of increasing pain, dehydration, and depression. This is particularly the case for older and infirm individuals.

Of the few high-quality randomized controlled trials, most have enrolled small numbers in single centers. A 2007 review confirmed that carbamazepine remains the first-choice drug, and pain relief is usually obtained within 4 to 24 hours.¹²⁵ The initial dose of 100 mg tid is increased every 48 hours in a stepwise manner until symptom relief or side effects occur. Patients should be warned of the potential for drowsiness, rash, and unsteadiness. A baseline full blood count is recommended because leukopenia occurs commonly and agranulocytosis rarely; treatment should be stopped immediately if the latter occurs. Although carbamazepine is usually effective at blood levels of 25 to 50 mg/L, the dose can be titrated to the maximum tolerated in resistant cases. Therapy should be maintained until the patient has been free of pain for at least 4 weeks, after which slow reduction of dose by decrements of 100 mg of carbamazepine each week may allow for complete withdrawal of the drug. For patients who experience limited efficacy or side effects, oxcarbazepine should be tried. This is a prodrug of arbamazepine and does not utilize the hepatic cytochrome system, thereby resulting in fewer drug interactions. Recent guidelines have suggested that lamotrigine and baclofen may be effective if carbamazepine and oxcarbazepine fail.^126,127 A small open label trial of pregabalin demonstrated positive results.¹²⁸ Combination therapy may be necessary but may aggravate drowsiness. Alternatively, phenytoin, clonazepam, or sodium valproate can be added. Polypharmacy should be avoided if possible because of additional side effects and problems with compliance.

Surgical intervention should be considered if medical treatment fails. Up to 50% of patients may eventually require some form of surgical treatment. Early referral should be considered when symptomatic control with pharmacotherapy proves difficult. There are two main options, rhizotomy or microvascular decompression.

Percutaneous treatments, including balloon compression, radiofrequency rhizotomy, and glycerol rhizolysis, are relatively safe and simple. Patients require only light anesthesia, and the procedure is carried out under radiographic screening control. Selective root lesioning is achieved if a stimulating electrode is employed, and this reduces the side effects (discussed later). Acute pain relief can be accomplished in more than 90% of patients, and this can be maintained in the long term with repeated treatments if necessary.¹²⁹ Glycerol, injected into the Meckel cave, acts as a neurotoxin. Atypical trigeminal neuralgia responds less well to treatments in general.

The main side effect is sensory loss (usually less with glycerol injection). Corneal hypoesthesia is a problem and may result in ulceration. Rarely there may be masseter weakness. Both forms of treatment have about 90% success, and the patient can be discharged home within 24 hours. Unfortunately, the reported recurrence rates are about 25%. In a study comparing glycerol rhizolysis and posterior fossa exploration, freedom from pain at 5 years was 59% and 68%, respectively.¹³⁰ Cheng and coworkers have recently reviewed the literature on these treatments.¹³¹

Gamma knife radiosurgery is the least invasive treatment but with unknown long-term outcomes as few data are available beyond 5 years of treatment. Rates of pain relief of 70% have been reported at 6 months after treatment; the effects are often delayed and facial numbness may occur.¹³²

Microvascular decompression involves major neurosurgery with a posterior fossa approach. This procedure was pioneered by Jannetta.¹³³ If a blood vessel is found in close association with the trigeminal root or deforming it, it is mobilized and a small sponge of polyvinyl chloride is interposed between the nerve and the vessel. This procedure is generally well tolerated by older patients who are otherwise medically fit for surgery.¹³⁴ Recurrence rates of up to 24% at 30 months after the procedure were reported in one study.¹³⁵ Overall, the recurrence of pain after any surgical procedure was 19% with a minimum 5-year follow-up, with microvascular decompression providing the greatest relief and patient satisfaction.¹³⁶

Glossopharyngeal Neuralgia

This syndrome has the same symptom characteristics as trigeminal neuralgia, but the pain is felt in the region of the tonsil and ear. Trigger factors include swallowing, coughing, and talking, and the distribution of the pain is in the sensory territory of the glossopharyngeal nerve and the auricular and pharyngeal branches of the vagus nerve. Rarely the patient may become unconscious during an attack because of asystole.³⁵ Neurologic examination is normal unless the syndrome is secondary to pathology such as neoplasm, infection, or inflammatory disease.

Treatment is the same as for trigeminal neuralgia with carbamazepine as first-choice pharmacotherapy. The medical treatment of this condition is less successful than in the case of trigeminal neuralgia, and surgery is more often undertaken.¹³⁷ If there is no improvement, microvascular dissection of the intracranial section of the glossopharyngeal nerve and upper two rootlets of the vagus can be undertaken.^138,139

Postherpetic Neuralgia

Postherpetic neuralgia occurs following 10% of attacks of shingles, but this figure rises to 50% in adults older than 60 years.¹⁴⁰ The most common site is the ophthalmic division of the trigeminal nerve. The virus has a predilection for the trigeminal (23% of cases¹⁴¹) and upper cervical ganglia, and in the acute stages the herpetic eruption is seen in the appropriate distribution. The Ramsay Hunt syndrome is caused by herpetic infection of the facial nerve. Excruciating pain may precede the eruption of vesicles by 1 to 3 days. The latter are seen over the external auditory meatus and mastoid process and may occur with edema and redness of the ear, making examination difficult. Occasionally, other cranial nerves may be affected with involvement of the trigeminal nerve, leading to loss of sensation on the face and numbness of the palate occurring when the ninth nerve is affected. A careful search for vesicles around the ear and in the mouth will make the diagnosis clear. There may also be involvement of the fourth, sixth, and oculomotor nerves,¹⁴² with the possibility of long-term paralysis.

The syndrome of postherpetic neuralgia is characterized by a constant burning or aching pain with occasional stabbing components and occurs following healing of the rash. It may take several weeks or months to emerge. There is sensory loss over the affected area, and invariably allodynia develops.

Treatment is symptomatic.¹⁴³ Antiviral therapy such as acyclovir was shown to provide marginal evidence for reduction of pain incidence at 1 to 3months following zoster onset. Famciclovir reduced the duration of the neuralgia but not its incidence, as did valacyclovir. Steroids had no effect on postherpetic neuralgia.^144,145 Amitriptyline taken at the onset may reduce the incidence of postherpetic neuralgia, but more trials need to be undertaken.¹⁴⁴ Acyclovir (800 mg five times daily) may be prescribed if the rash is extensive or if there is a threat to eyesight. Opiate analgesia may be required. Once neuralgia is established, amitriptyline is of proven benefit,^146,147 and carbamazepine may help to control the stabbing component of the pain. Relief of pain may be gained in up to 80% of cases. Nortriptyline and desipramine may be better tolerated, causing less sedation; the former has been shown to be as effective as amitriptyline.¹⁴⁸ Transcutaneous electrical nerve stimulation (TENS) may sometimes be useful. Topical capsaicin cream has had variable success.^149,150 Topical lidocaine patch 5% has been shown to be efficacious in patients with evidence of allodynia. The patch can be cut to any shape and placed over active lesions; the main side effect seems to be mild local skin irritation. Both gabapentin and pregabalin are licensed for the treatment of this condition,^151,152 which is notoriously difficult to treat and may require multidisciplinary input.¹⁵³