Headache and Facial Pain

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). 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.

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:

• One or more fully reversible aura symptoms

• Aura developing over more than 4 minutes

• Aura lasting less than 60 minutes

• Headache following aura with a free interval of less than 60 minutes

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

• Unilateral headache

• Pulsating quality

• Nausea

• Photophobia and phonophobia

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. 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, 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. Somatosensory phenomena, typically paresthesias with anatomic march of symptoms, may occur, and motor disturbance may result in hemiparesis. Aphasia has also been reported. 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 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 series and is more common in vertebrobasilar ischemia. 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 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. The pain may be unilateral in 60% of cases but bilateral at the outset in up to 40%. 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.

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, 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, hormone replacement treatment in postmenopausal women, irregular meals, and a change in sleep habit. 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. 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. 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 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 5HT ₁ 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 injection and up to 65% after a tablet dose. 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. 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. 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.

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. 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. Amitriptyline is most commonly used, although fluoxetine has fewer anticholinergic side effects and causes less weight gain. Paroxetine may be a suitable alternative when anxiety is a factor. 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.

Sodium valproate (0.6 to 2.5 g daily) is well tolerated, and there is clinical trial evidence of efficacy. 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.

Calcium channel antagonists are not licensed for migraine prophylaxis in the United Kingdom but have been shown to be of benefit. 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.

Of the serotonin antagonists, the two most commonly prescribed are pizotifen and methysergide. Pizotifen is a 5HT ₂ 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. Methysergide is also a 5HT ₂ antagonist with some affinity for the 5HT ₁ receptor. It is effective prophylaxis in up to 60% of migraineurs, possibly with better results in those with migraine with aura. 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.

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 trials and, to date, the safety data are encouraging. Patients should be selected carefully and published injection protocols adhered to.

Diagnosis

Trigeminal neuralgia is diagnosed clinically. It rarely begins before the age of 30 years, has a prevalence of 0.1 to 0.2/1000 and an incidence of up to 20/100,000/year after the age of 60 years, and the female-to-male ratio is 3 : 2. Higher incidences are reported up to 28.9/100,000/year in the Netherlands. The symptoms are pathognomonic. The pain is periodic, of high intensity, and lancinating, lasting from 20 to 30 seconds and followed by a period of relief lasting a few seconds to a minute, which may be followed by further paroxysms of pain. The pain usually commences in the maxillary and mandibular divisions of the trigeminal nerve, and in fewer than 5% of cases it begins in the ophthalmic division. In some 10% to 15% of cases, all the divisions are involved and the symptoms may be bilateral in 3% to 5%. Apart from the quality and characteristic site of pain, the patient can usually identify trigger factors such as brushing the teeth, washing the face, shaving, biting, chewing, or even a gust of cold wind on the face. Avoidance behavior is common. The most recent Classification of Headache Disorders includes the diagnostic category of classical trigeminal neuralgia with concomitant persistent facial pain, previously known as atypical trigeminal neuralgia or trigeminal neuralgia type II. The prognosis for remission in this form is less good, and in fewer cases is it possible to demonstrate neurovascular compression (see later). Central sensitization has been proposed as a factor.

The pain of trigeminal neuralgia may occur daily for weeks or months followed by remission of varying periods. Unfortunately there is a tendency for the disorder to deteriorate, with increased frequency of attacks increasingly resistant to treatment. Clinical examination should be normal, and any loss of facial sensation should be promptly investigated, preferably with gadolinium-enhanced magnetic resonance imaging (MRI) of the brain and trigeminal system, to rule out a compressive lesion of the nerve. Autonomic symptoms are not present in this condition. The presence of autonomic activation and pain primarily in the first division of the nerve is more likely to represent one of the trigeminal autonomic cephalalgias than trigeminal neuralgia.

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 associates 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.” 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. 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. 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. 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. 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. A small open label trial of pregabalin demonstrated positive results. 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. 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. Cheng and coworkers have recently reviewed the literature on these treatments.

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.

Microvascular decompression involves major neurosurgery with a posterior fossa approach. This procedure was pioneered by Jannetta. 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. Recurrence rates of up to 24% at 30 months after the procedure were reported in one study. 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.