Practical neurology Part 7 - Recurrent headaches with visual disturbance

Headache, particularly migraine, is the commonest neurological problem with which patients present to general practitioners and neurologists. Comprehensive history-taking offers the best chance of establishing whether a headache is primary (idiopathic) or secondary to an underlying condition. Most headaches encountered in practice are primary, either migraine headache or tension-type headache. Less common primary headaches include cluster headache, primary cough and exertional headache, primary sex headache and primary thunderclap headache. The second edition of The international classification of headache disorders provides a comprehensive description of the many types of headache.1

Important features in the patient history are: location, temporal pattern and quality of the pain; presence of associated symptoms; and presence of specific triggers (eg, exertion, coughing, sneezing). Red flags that may indicate a secondary headache are summarised by the mnemonic SNOOP4 (Box 1).2 When any of these red flags are present, brain imaging is mandatory (computed tomography or magnetic resonance, depending on how or when the patient presents, resource availability and clinical urgency). However, for most patients with migraine, brain imaging is not necessary.

Migraine headache is defined by the features of the headache and the presence of associated symptoms (Box 2).1 Migraine is considered a primary disorder of the central nervous system (CNS). It is a chronic disorder with episodic manifestations, and it is often familial and has a strong genetic component. Episodic migraine affects up to 18% of women and 6% of men.

Neck pain is also very common in migraine — up to 60% of patients complain of occipital or neck pain during their migraine attacks and this is nearly always a referred pain. Pathological conditions of the upper cervical spine, which are uncommon, can cause headache; however, disorders of the cervical spine are not a common cause of migraine.

The manifestations of migraine are believed to be due to increased cortical neuronal excitability, owing to defective modulatory pathways in the brainstem and possibly other structures in the CNS. In particular, the aura of migraine is not due to vasospasm — it is due to altered neuronal activity called “cortical spreading depression”.3-5

For Rachel, the other features of her attacks that make the diagnosis of migraine definite are the change in sides of both the headache and aura. In addition to the headache phase, there are often premonitory and resolution phases.3,6 In some patients with migraine, nausea and vomiting are the most disabling features; in others, it is the aura or the severity of the headache.

Acute migraine attacks can be severely disabling, and chronic migraine is even more disabling. The World Health Organization ranks migraine as 19th worldwide of all the causes of years lived with a disability due to a medical condition and eighth of the mental and neurological disorders in terms of disability. In high-income countries such as Australia, the total disability due to migraine is said to be more than 1.5 times that due to multiple sclerosis and Parkinson disease combined and almost three times that due to epilepsy.7 However, it is considerably under-recognised, underdiagnosed and undertreated worldwide.

Chronic migraine is diagnosed when a patient known to have migraine without aura has headaches on 15 or more days per month for at least 3 months, of which eight or more per month meet the criteria for migraine without aura or respond to migraine-specific acute medication (triptans or ergot preparations).10 Its prevalence is 2% worldwide11 and patients with chronic migraine are more disabled, have a lower quality of life, have a higher rate of psychiatric comorbidity and use significantly more health care resources than patients with episodic migraine.12 About 2.5% of patients with episodic migraine will progress to chronic migraine over a year. Risk factors for progression include female sex, lower socioeconomic status and increased caffeine intake.11 Medication overuse is also an important contributor to development of chronic migraine.

MOH is likely in patients who have headache on 15 or more days per month for more than 3 months, have been using acute medication therapies frequently and have had worsening of the headaches while using the acute medication.13 Frequent use of ergot preparations, opiates, triptans or combination analgesics is defined as 10 or more days per month and for simple analgesics 15 or more days per month. Many patients with MOH have daily headaches and take acute medication every day or nearly every day.

Prophylactic therapies are usually ineffective for migraine if MOH is present, and MOH is a risk factor for progression from episodic migraine to chronic migraine. An accurate patient history of all acute medication use (including paracetamol) and caffeine is needed. Some agents, including triptans, can lead to MOH and chronic migraine more quickly than others, such as simple analgesics or non-steroidal anti-inflammatory drugs (NSAIDs). In Australia, overuse of codeine-containing agents is particularly common and carries the added potential risk of dependency. Management of MOH involves education of the patient, appropriate prophylactic medication and withdrawal of the offending acute medication therapy. MOH can usually be managed in the outpatient setting, but hospital admission is sometimes needed for a dihydroergotamine (DHE) or lignocaine infusion.

The risk of stroke is increased in patients with migraine. According to a recent meta-analysis, there is a twofold increased risk of ischaemic stroke which occurs in patients with migraine with aura but not in patients with migraine without aura.14 Women are more at risk, particularly if they are young (under 45 years), smokers and taking the oral contraceptive pill. The overall absolute risk is, however, quite low, and stroke in young patients with migraine is rare.15

Patients with episodic migraine need to be given an explanation of the condition and a treatment plan, and the treatment goals need to be discussed. Online resources for patients are available from Headache Australia (http://headacheaustralia.org.au, see the iManage Migraine app), the World Headache Alliance (http://www.w-h-a.org) and the BMJ (http://www.bmj.com/multimedia/video/2011/02/05/migraine-pain-and-pressure). Treatment options for complicating factors are shown in Box 5.

Keeping a diary: A headache diary is invaluable for establishing baseline headache frequency, identifying patterns (such as an association of migraine attacks with menstruation), quantifying lost work time, monitoring treatment response, and identifying MOH.

Identifying triggers: The commonest triggers in migraine without aura are stress, foods (eg, alcohol, chocolate, dairy foods [particularly cheese]) and menstruation.6 In migraine with aura, a visual stimulus (eg, flickering light) is a common trigger. Triggers should generally be avoided, although an alternative behavioural approach of trying to cope with some triggers has been suggested.19 However, many patients cannot identify triggers, and some triggers may be complex (eg, a period of stress coinciding with menstruation). Only about 10% of women with migraine have pure menstrual migraine, where they only have attacks during menstruation.

Acute treatment: It is important to tailor the acute treatment to both the individual patient and to the different attacks experienced by the individual patient. Acute medication therapies in migraine are either non-specific (paracetamol, aspirin or other NSAIDs) or migraine-specific (ergot preparations and triptans) (Box 6). Initial treatment should be with simple analgesics and NSAIDs, taken at the earliest possible time (at onset of aura, if present). Suppositories can be helpful in patients with significant nausea or those who are already vomiting.

Antiemetic and prokinetic drugs are helpful in treating associated nausea and may improve the efficacy of analgesics, NSAIDs and triptans by overcoming associated gastroparesis. Antiemetics may also reduce the severity of the headache and should always be used if there is nausea. Local guidelines list oral domperidone 10–20 mg (grade B evidence), metoclopramide 10–20 mg (grade B evidence) and prochlorperazine 10 mg, and prochlorperazine 25 mg suppositories.17 Domperidone is much less likely than metoclopramide or prochlorperazine to cause a dystonic reaction or akathisia. Although only PBS listed for cytotoxic chemotherapy-related nausea and vomiting, ondansetron wafers are often the most effective antiemetic for some patients; however, cost is an issue.

Second-line agents for acute treatment are ergot preparations and triptans. No oral or rectal ergot preparations are commercially available in Australia, but compounded ergot preparations can be obtained. Triptans should be used if first-line agents have been ineffective after 1–2 hours or ineffective in previous attacks. Unlike the other acute medication therapies, triptans are generally ineffective if taken at the aura stage, but are effective during the headache phase.

Parenteral agents may be required for patients whose condition fails to respond to oral agents or who are vomiting and cannot tolerate oral agents. DHE 0.5–1 mg can be given by subcutaneous, intramuscular or intravenous injection — always with an antiemetic — or sumatriptan 6 mg can be given by subcutaneous injection.

Emerging treatments: With new treatments emerging, this is an exciting time in the field of migraine management. On the horizon are new classes of non-vasoconstrictor drugs, calcitonin gene-related peptide (CGRP) antagonists (“gepants”) and serotonin 1F receptor agonists, as well as novel neuromodulation techniques such as occipital nerve stimulators and transcranial magnetic stimulation.20

Status migrainosus is a debilitating migraine attack that lasts more than 72 hours and is refractory to the patient’s usual treatments.1 Hospital admission and treatment of dehydration with intravenous fluids are usually necessary. Parenteral administration of DHE, with an antiemetic, can be effective in this situation. Some guidelines suggest using 8-hourly intravenous injections of 0.25–1 mg DHE.17 However, in our experience, it is better tolerated as an infusion of 3 mg DHE over 24 hours (which can be titrated up or down according to response and adverse effects). Other options include parenteral chlorpromazine, droperidol, prochlorperazine and sumatriptan.17

Patients who have three or more migraine attacks per month are usually considered as being suitable for prophylaxis. However, prophylaxis may also be warranted in patients who have fewer attacks — for example, if the attacks last days, do not respond to acute treatment, cause lost work time or are otherwise disabling. Conversely, patients who have more than three attacks per month that are all reliably aborted by acute treatment may not need prophylaxis. The aim of prophylactic treatment is not only to reduce the frequency of attacks but also to reduce severity and duration of the attacks and to render the attacks more amenable to acute treatment. The initial choice of prophylactic agent is usually based on side-effect profiles and patient characteristics. First-line prophylactic agents are serotonin reuptake inhibitors such as amitriptyline, other tricyclic antidepressants, 5-HT2-receptor antagonists (pizotifen) and β-blockers (propranolol and metoprolol) (Box 7).17,21-23 The β-blockers, however, are best avoided in patients who have frequent migraine with aura as they can worsen the aura.

It is appropriate for a general practitioner or other physician to initiate prophylaxis with first-line agents, but, if these are ineffective or cause adverse effects, referral to a neurologist is appropriate. Prophylactic agents should be trialled for at least a month at the highest tolerated dose before being deemed ineffective. Once good control has been achieved for at least 6 months, it may be possible to wean the patient off the drug. In more severely affected patients (eg, those with a longstanding history of very frequent attacks), a longer period of prophylactic therapy or combination prophylactic therapy may be needed.

In some patients with chronic migraine, the condition responds to treatment with topiramate11 or repeated injection of onabotulinumtoxinA into multiple sites in the head and neck.24 A multidisciplinary approach, including behavioural pain management, to chronic migraine and other refractory headaches (eg, in a dedicated headache clinic) is more likely to be successful than other approaches.25