APPROACH TO THE PATIENT: Chronic Daily Headache
The first step in the management of patients with CDH is to diagnose any secondary headache and treat that problem (Table 9-3). This can sometimes be a challenge where the underlying cause triggers a worsening of a primary headache. For patients with primary headaches, diagnosis of the headache type will guide therapy. Preventive treatments such as tricyclics, either amitriptyline or nortriptyline at doses up to 1 mg/kg, are very useful in patients with CDH arising from migraine or tension-type headache or where the secondary cause has activated the underlying primary headache. Tricyclics are started in low doses (10–25 mg) daily and may be given 12 h before the expected time of awakening in order to avoid excess morning sleepiness. Anticonvulsants, such as topiramate, valproate, flunarizine (not available in the United States), and candesartan are also useful in migraine.
MANAGEMENT OF MEDICALLY INTRACTABLE DISABLING PRIMARY CHRONIC DAILY HEADACHE The management of medically intractable headache is difficult. Currently there are a number of promising neuromodulatory approaches, such as occipital nerve stimulation, which appears to modulate thalamic processing in migraine, and has also shown promise in chronic cluster headache, short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), and hemicrania continua (Chap. 34). Single-pulse transcranial magnetic stimulation is in use in Europe and is approved for migraine with aura in the United States. Other modalities are discussed in Chap. 34.
MEDICATION-OVERUSE HEADACHE Overuse of analgesic medication for headache can aggravate headache frequency, markedly impair the effect of preventive medicines, and induce a state of refractory daily or near-daily headache called medication-overuse headache. A proportion of patients who stop taking analgesics will experience substantial improvement in the severity and frequency of their headache. However, even after cessation of analgesic use, many patients continue to have headache, although they may feel clinically improved in some way, especially if they have been using opioids or barbiturates regularly. The residual symptoms probably represent the underlying primary headache disorder, and most commonly, this issue occurs in patients prone to migraine.
Management of medication overuse: outpatients For patients who overuse medications, it is essential that analgesic use be reduced and eliminated. One approach is to reduce the medication dose by 10% every 1–2 weeks. Immediate cessation of analgesic use is possible for some patients, provided there is no contraindication. Both approaches are facilitated by the use of a medication diary maintained during the month or two before cessation; this helps to identify the scope of the problem. A small dose of a nonsteroidal anti-inflammatory drug (NSAID) such as naproxen, 500 mg bid, if tolerated, will help relieve residual pain as analgesic use is reduced. NSAID overuse is not usually a problem for patients with daily headache when a NSAID with a longer half-life is taken once or twice daily; however, overuse problems may develop with more frequent dosing schedules or shorter acting NSAIDS. Once the patient has substantially reduced analgesic use, a preventive medication should be introduced. It must be emphasized that preventives generally do not work in the presence of analgesic overuse. The most common cause of unresponsiveness to treatment is the use of a preventive when analgesics continue to be used regularly. For some patients, discontinuing analgesics is very difficult; often the best approach is to directly inform the patient that some degree of pain is inevitable during this initial period.
Management of medication overuse: inpatients Some patients will require hospitalization for detoxification. Such patients have typically failed efforts at outpatient withdrawal or have a significant medical condition, such as diabetes mellitus, which would complicate withdrawal as an outpatient. Following admission to the hospital, acute medications are withdrawn completely on the first day, in the absence of a contraindication. Antiemetics and fluids are administered as required; clonidine is used for opioid withdrawal symptoms. For acute intolerable pain during the waking hours, aspirin, 1 g IV (not approved in United States), is useful. IM chlorpromazine can be helpful at night; patients must be adequately hydrated. Three to 5 days into the admission, as the effect of the withdrawn substance wears off, a course of IV dihydroergotamine (DHE) can be used. DHE, administered every 8 h for 5 consecutive days, can induce a significant remission that allows a preventive treatment to be established. 5-HT3 antagonists, such as ondansetron or granisetron, or the neurokinin receptor antagonist, aprepitant, may be required with DHE to prevent significant nausea, and domperidone (not approved in the United States) orally or by suppository can be very helpful. Avoiding sedating or otherwise side effect prone antiemetics is helpful.
NEW DAILY PERSISTENT HEADACHE New daily persistent headache (NDPH) is a clinically distinct syndrome; its causes are listed in Table 9-4.
Clinical presentation The patient with NDPH presents with headache on most if not all days, and the patient can clearly, and often vividly, recall the moment of onset. The headache usually begins abruptly, but onset may be more gradual; evolution over 3 days has been proposed as the upper limit for this syndrome. Patients typically recall the exact day and circumstances of the onset of headache; the new, persistent head pain does not remit. The first priority is to distinguish between a primary and a secondary cause of this syndrome. Subarachnoid hemorrhage is the most serious of the secondary causes and must be excluded either by history or appropriate investigation (Chap. 33).
Secondary NDPH Low CSF volume headache In these syndromes, head pain is positional: it begins when the patient sits or stands upright and resolves upon reclining. The pain, which is occipitofrontal, is usually a dull ache but may be throbbing. Patients with chronic low CSF volume headache typically present with a history of headache from one day to the next that is generally not present on waking but worsens during the day. Recumbency usually improves the headache within minutes, and it can take only minutes to an hour for the pain to return when the patient resumes an upright position.
The most common cause of headache due to persistent low CSF volume is CSF leak following LP. Post-LP headache usually begins within 48 h but may be delayed for up to 12 days. Its incidence is between 10 and 30%. Beverages with caffeine may provide temporary relief. Besides LP, index events may include epidural injection or a vigorous Valsalva maneuver, such as from lifting, straining, coughing, clearing the eustachian tubes in an airplane, or multiple orgasms. Spontaneous CSF leaks are well recognized, and the diagnosis should be considered whenever the headache history is typical, even when there is no obvious index event. As time passes from the index event, the postural nature may become less apparent; cases in which the index event occurred several years before the eventual diagnosis have been recognized. Symptoms appear to result from low volume rather than low pressure: although low CSF pressures, typically 0–50 mmH2O, are usually identified, a pressure as high as 140 mmH2O has been noted with a documented leak.
Postural orthostatic tachycardia syndrome (POTS; Chap. 41) can present with orthostatic headache similar to low CSF volume headache and is a diagnosis that needs consideration in this setting.
When imaging is indicated to identify the source of a presumed leak, an MRI with gadolinium is the initial study of choice (Fig. 9-1). A striking pattern of diffuse meningeal enhancement is so typical that in the appropriate clinical context the diagnosis is established. Chiari malformations may sometimes be noted on MRI; in such cases, surgery to decompress the posterior fossa usually worsens the headache. Spinal MRI with T2 weighting may reveal a leak, and spinal MRI may demonstrate spinal meningeal cysts whose role in these syndromes is yet to be elucidated. The source of CSF leakage may be identified by spinal MRI with appropriate sequences, by CT, or increasingly by MR myelography. Less used now, 111In-DTPA CSF studies in the absence of a directly identified site of leakage, may demonstrate early emptying of 111In-DTPA tracer into the bladder or slow progress of tracer across the brain suggesting a CSF leak.
Initial treatment for low CSF volume headache is bed rest. For patients with persistent pain, IV caffeine (500 mg in 500 mL of saline administered over 2 h) can be very effective. An electrocardiogram (ECG) to screen for arrhythmia should be performed before administration. It is reasonable to administer at least two infusions of caffeine before embarking on additional tests to identify the source of the CSF leak. Because IV caffeine is safe and can be curative, it spares many patients the need for further investigations. If unsuccessful, an abdominal binder may be helpful. If a leak can be identified, an autologous blood patch is usually curative. A blood patch is also effective for post-LP headache; in this setting, the location is empirically determined to be the site of the LP. In patients with intractable pain, oral theophylline is a useful alternative; however, its effect is less rapid than caffeine.
Raised CSF pressure headache Raised CSF pressure is well recognized as a cause of headache. Brain imaging can often reveal the cause, such as a space-occupying lesion. NDPH due to raised CSF pressure can be the presenting symptom for patients with idiopathic intracranial hypertension (pseudotumor cerebri) without visual problems, particularly when the fundi are normal. Persistently raised intracranial pressure can trigger chronic migraine. These patients typically present with a history of generalized headache that is present on waking and improves as the day goes on. It is generally worse with recumbency. Visual obscurations are frequent. The diagnosis is relatively straightforward when papilledema is present, but the possibility must be considered even in patients without funduscopic changes. Formal visual field testing should be performed even in the absence of overt ophthalmic involvement. Headache on rising in the morning or nocturnal headache is also characteristic of obstructive sleep apnea or poorly controlled hypertension.
Evaluation of patients suspected to have raised CSF pressure requires brain imaging. It is most efficient to obtain an MRI, including an MR venogram, as the initial study. If there are no contraindications, the CSF pressure should be measured by LP; this should be done when the patient is symptomatic so that both the pressure and the response to removal of 20–30 mL of CSF can be determined. An elevated opening pressure and improvement in headache following removal of CSF are diagnostic.
Initial treatment is with acetazolamide (250–500 mg bid); the headache may improve within weeks. If ineffective, topiramate is the next treatment of choice; it has many actions that may be useful in this setting, including carbonic anhydrase inhibition, weight loss, and neuronal membrane stabilization, likely mediated via effects on phosphorylation pathways. Severely disabled patients who do not respond to medical treatment require intracranial pressure monitoring and may require shunting.
Posttraumatic headache A traumatic event can trigger a headache process that lasts for many months or years after the event. The term trauma is used in a very broad sense: headache can develop following an injury to the head, but it can also develop after an infectious episode, typically viral meningitis, a flulike illness, or a parasitic infection. Complaints of dizziness, vertigo, and impaired memory can accompany the headache. Symptoms may remit after several weeks or persist for months and even years after the injury. Typically the neurologic examination is normal and CT or MRI studies are unrevealing. Chronic subdural hematoma may on occasion mimic this disorder. Posttraumatic headache may also be seen after carotid dissection and subarachnoid hemorrhage and after intracranial surgery. The underlying theme appears to be that a traumatic event involving the pain-producing meninges can trigger a headache process that lasts for many years.
Other causes In one series, one-third of patients with NDPH reported headache beginning after a transient flulike illness characterized by fever, neck stiffness, photophobia, and marked malaise. Evaluation typically reveals no apparent cause for the headache. There is no convincing evidence that persistent Epstein-Barr virus infection plays a role in NDPH. A complicating factor is that many patients undergo LP during the acute illness; iatrogenic low CSF volume headache must be considered in these cases.
Treatment Treatment is largely empirical. Tricyclic antidepressants, notably amitriptyline, and anticonvulsants, such as topiramate, valproate, and gabapentin, have been used with reported benefit. The monoamine oxidase inhibitor phenelzine may also be useful in carefully selected patients. The headache usually resolves within 3–5 years, but it can be quite disabling.