A review of the treatment of primary headaches. Part I: Migraine

Finding the best treatment for a patient's migraine is often a problem in clinical practice since the condition is very common, often debilitating and may prove refractory to therapy. Over recent years, more effective migraine treatments have been found and validated, and the traditional remedies have undergone controlled testing. This article reviews the various therapies available for both the acute treatment and prevention of migraine. Treatments often effective against migraine attacks are: aspirin, analgesics, non steroid anti-inflammatory drugs (NSAIDs), ergot derivatives and sumatriptan. Five main classes of prophylactic drug are currently used: beta-blockers, calcium antagonists, serotonin modulators, NSAIDs and ergot compounds. Biofeedback, one of the most efficacious non-pharmacological preventive treatments of migraine, is also discussed. The variables influencing the choice of acute and preventive treatments, including contraindications and drug availability, are also described in order to provide a practical and up-to-date guide to migraine therapy.     

Medical treatment of migraine: from mechanisms of action to contraindications

Management of migraine patients with or without aura must include appropriate medication to treat the attack and long-term preventive therapy, especially if the frequency of the attacks is greater than 2-4 per month. In both cases the choice of treatment depends on its efficacy and side effects. With regard to acute drug therapy, group studies do not suggest that ergot derivatives and sumatriptan are superior to simple analgesics and anti-inflammatory drugs, particularly if a prokinetic agent is added. These new substances are indicated for severe attacks refractory to more conventional therapy. Chronic drug abuse may induce drug-induced or rebound headaches. As regards long-term prophylaxis, group studies suggest that calcium antagonists and 5-HT-influencing drugs are superior concerning attacks frequency to beta-blocking agents, but involve very frequent side effects (weight gain and somnolence). Interesting preliminary results have also been reported with valproate and enalapril, which will confirmation by controlled studies. Finally, the choice of drug must take into account the patient's comorbidities (cardiovascular diseases, asthma, diabetes etc).     

Local and systemic eosinophil activation in allergic fungal sinusitis

Research into the genetics of migraine remains difficult because of the involvement of polygenetic and environmental factors. The discovery of the gene for familial hemiplegic migraine on chromosome 19p 13 is an important step forward. This brain specific P/Q-type calcium channel alpha 1-subunit gene opens new avenues for studying the genetics of migraine, the pathophysiology of the onset of migraine attacks and the development of novel specific prophylactic drugs.     

Menstruation, sex hormones, and migraine

All women with migraine are susceptible to the effects of hormonal changes. For a minority with menstrual migraine, fluctuating hormones of the normal ovarian cycle are a specific trigger, particularly during perimenopause. The author proposes that the term menstrual migraine should be restricted to migraine attacks occurring on day 1 +/- 2 days of the menstrual cycle with freedom from migraine during the rest of the cycle. This definition is compatible with the mechanism of estrogen withdrawal. Other mechanisms such as prostaglandin release also may be important for some women. The changing hormonal environment at various stages of life provides further evidence of the role of estrogen in migraine. Treatments that stabilize hormone levels in the form of estrogen supplementation for menstrual migraine, elimination of the pill-free week, and adequate, stable levels of estrogen for HRT, all are associated with an improvement in migraine. The control of the menstrual cycle, however, is extremely complex, and until further studies are undertaken using strict criteria, the mechanism of migraine triggered by hormonal events remains uncertain.     

The use of drugs in migraine

Drugs may be given either for treatment of the acute attack or as prophylaxis. Those most commonly used for the acute attack are analgesics, anti-emetics and ergotamine tartrate. A recent work (Volans, 1974) has shown that absorption may be impaired during a migraine attack. It is important therefore that not only is the analgesic given in an easily absorbed form but that a drug such as metaclopromide should be given to help restore the normal activity of the gastro-intestinal tract. Patients having one or more attacks of migraine a week may need prophylactic treatment. The drugs now used include: Methysergide, should only be used for severe cases when no other treatment has been found helpful. Dihydroergotamine, the vasoconstrictor activity is less than in ergotamine tartrate and can therefore be used prophylactically. Pizotifen, possesses powerful anti-serotonin properties. It also has marked antihistamine and antitryptamine properties as well as being a central sedative and anti-depressant. Clonidine, in doses of 1 mugm/Kg renders the blood vessels less sensitive to circulating amines and seems to be effective in about one third of patients with classical or common migraine. Sympathetic Blocking Agents: alpha-blockers: indoramine has recently given some good results; beta-blockers: such as propanolol and pindolol have also been used. Full trials of all the substances are now in progress. Tranquilisers and anti-depressants, two of those commonly used are diazepam and amitryptiline. In either cases a small dose only should be used. Anticonvulsants, phenytoin in doses of 50-100 mgs per day is sometimes helpful particularly in children or in those who have abnormal electroencephalograms.     

Alternative medicine. Unclear limits for what is allowed. What is "science and proven experience?"

The questions concerning both control of migraine attacks and prophylaxis of migraine with standard drugs are considered. The results of own observations are presented. There are predictors of either elevation or a decrease of efficiency of the preparations used.     

Vertigo

Vertigo is a subtype of dizziness, which results from an imbalance within the vestibular system. This seminar focuses on three common presentations of vertigo: prolonged spontaneous vertigo, recurrent attacks of vertigo, and positional vertigo. The patient's history is usually the key to differentiation of peripheral and central causes of vertigo. The most common cause of vertigo, benign paroxysmal positional vertigo, can be cured with a simple positional manoeuvre. Other common causes of vertigo include vestibular neuritis, Ménière's syndrome, migraine, and vertebrobasilar insufficiency. Treatment should be directed at the underlying cause whenever possible, but antivertiginous and antiemetic drugs can suppress symptoms when a specific cause cannot be found. These drugs are generally not indicated for long-term daily use, however, since they may interfere with the normal compensation process.     

Total 5-hydroxyindoles in blood related to migraine attacks

The total 5-hydroxyindoles (5HI) in whole blood were measured in 20 migraine patients during spontaneous migraine attacks and in headache-free periods. A statistically significant fall in blood 5-HI was found during headache in 17 patients suffering from classical and common migraine. In one patient with complicated migraine no change was found, and in two patients, one with common migraine and one with migraine and associated symptoms, there was a rise in total blood 5-HI during migraine attacks. The results are compared with previous findings in this field, and it is suggested that during migraine attacks there might be a rise in the plasma 5-HI. The possibility of using the 5-HI fall during spontaneous migraine attacks as a simple test for the diagnosis of migraine is discussed.     

Vertigo and migraine

Vertigo consists of a variety of syndromes and can be due to many etiologies. One of these causes is migraine, which in our experience is often overlooked, although migrainous vertigo is well known in the literature. Vertigo in migraine can occur as aura or during the headache phase, or independent of the attacks as aura without headache. The aim of this retrospective study was to analyze cases with vertigo and migraine: 23 (8%) of 298 patients with migraine examined in a neurological outpatient department also had rotational vertigo. 48% of these patients had vertigo independent from typical migraine headache. Two types of vertigo were found: permanent vertigo, and vertigo with the characteristics of paroxysmal positional vertigo. 57% of the vertiginous attacks lasted hours, 26% even days, and 17% minutes. Most of the patients had several attacks of vertigo, some involving up to 30 episodes. To recognize migraine as a cause of vertigo has therapeutic implications. Most of our patients with vertigo and migraine showed a good response to antimigraine therapy.     

Beneficial effects of Helicobacter pylori eradication on migraine

BACKGROUND/AIMS: Migraine is a commonly unilateral throbbing headache, which has been associated with disorders of the vascular tone. Helicobacter pylori, the most relevant cause of gastritis and peptic ulcer, has been recently associated with a typical functional vascular disorder such as primary Raynaud phenomenon. The aim of this study was to assess the prevalence of H. pylori for patients affected by migraine and the effects of H. pylori eradication on migraine symptoms. METHODOLOGY: Two-hundred and twenty-five patients were consecutively enrolled between October 1996 and January 1997. H. pylori was assessed by 13C-urea breath test. Infected subjects were eradicated of the bacterium; frequency, intensity and duration of attacks of migraine were assessed during a 6 month follow-up period. RESULTS: H. pylori was detected in 40% of the patients. Eighty-three percent of the patients who underwent therapy were eradicated. Intensity, duration and frequency of attacks of migraine were significantly reduced in all eradicated patients. CONCLUSIONS: H. pylori is common in subjects with migraine. Bacterium eradication causes a significant decrease in attacks of migraine. The reduction of vasoactive substances produced during infection may be the pathogenetic mechanism underlying the phenomenon.     

Migraine--diagnosis, differential diagnosis and therapy

Migraine is caused by intermittent brain dysfunction. Attacks result in severe unilateral headache with nausea, vomiting, photophobia, phonophobia and general weakness. The prevalence of migraine is 12 to 20% in women and 8 to 12% in man. Treatment of an acute attack is done by antiemetics in combination with analgesics. Severe migraine attacks are treated with ergotamine or sumatriptan. Parenteral treatment is performed most efficiently and safely with i.v. ASA. Frequent and severe attacks require prophylaxis. Drugs of first choice are metoprolol, propranolol, flunarizine and cyclandelate. Substances of second choice are valproic acid, DHE, pizotifen, methysergide and magnesium. Homeopathic remedies are not superior to placebo. Nonpharmacological treatment consists of sport therapy and muscle relaxation techniques.     

Menstrual migraine. Methods of prevention and control

In many women, migraine headaches are clearly linked to estrogen levels: the incidence rises at the menarche; attacks may be precipitated by falling estrogen levels before menses; and symptoms usually improve during pregnancy when there are noncyclic high levels of estrogen. Decreased estrogen production in the perimenopausal phase may trigger an exacerbation of migraine. However, after menopause when estrogen levels are noncyclic and low, there may be an improvement in migraine. The falling estradiol level rather than the absolute level provides the trigger for menstruation-associated migraine. Treatment involves both prophylactic and acute measures. Therapy for an acute attack is similar to that for nonmenstrual migraine. Sumatriptan is equally effective for both nonmenstrual and menstrual migraine.     

Management of children with epiglottitis during transport: analysis of a survey

Naproxen is an anti-inflammatory drug widely used in the management of pain and in the treatment of migraine and headache. As gastrointestinal disturbances are a common feature of migraine, the aim of this study was to evaluate the absorption and the efficacy of naproxen administered during migraine attacks. Ten patients were treated with 500 mg of a soluble form of naproxen during and between migraine attacks. Clinical parameters and drug plasma levels were recorded at scheduled times. Pain reduction, from severe to mild was evident by 6.5 +/- 3.4 hours and the total pain score showed a reduction from 2 hours onwards. Pharmacokinetic data showed a slight delay in drug absorption during attacks (absorption half-life and time of maximum drug concentration were increased during attacks), but overall bioavailability of naproxen, as reflected by area under the curve (AUC) and maximum plasma drug concentration were unchanged. Since pain relief was reported, it may be concluded that delayed absorption has little or no influence on the therapeutic effect of naproxen in migraine attacks in fasting patients.     

Magnesium in migraine. Results of a multicenter pilot study

BACKGROUND: Numerous experiments and clinical observations have credited magnesium with a positive influence on the incidence of migraine attacks. METHODS: With the aim of testing this hypothesis, a doubleblind, cross-over multicenter pilot study was initiated. The study contained 43 migraine patients who met the criteria of the international Headache Society. INTERVENTIONS: Administration of 600 mg magnesium/day in the form of trimagnesium dieitrate for prophylaxis. RESULTS: Under this medication, a significant reduction in the incidence of migraine attacks was observed. Although the level of effectiveness of the regimen does not appear to be as high as that of presently approved migraine prophylactic substances, a very low rate of side effects can be expected. CONCLUSION: The working hypothesis to the effect that magnesium may be useful in the prevention of migraine attacks has been confirmed by the pilot study. Further studies aimed at determining dosage and enabling a further differentiation of patient material are in preparation.     

Migraine and stroke]

When young patients suffer a stroke the etiology often differs from that found in the elderly. One of the risk factors for stroke in young people could possibly be migraine. The first author to describe what was probably a migrainous cerebral infarction was Wepfer, in 1727. In recent years, cases of stroke in migraineurs have been frequently reported. Extensive cohort studies and smaller, well-conducted case-control studies seem to confirm that migraine is a risk factor for stroke. However, the risk is only moderately increased, perhaps doubled. Among women under the age of 45, the correlation is greater with a threefold increased risk of stroke in a migraineur; it is even greater in patients suffering attacks of migraine with aura. Pure migrainous infarctions are probably rare and reports are perhaps exaggerated in the literature. Cerebral ischaemia may lead to symptomatic migraine attacks. Overall, the absolute risk of stroke is small enough to validate the opinion that migraine is a benign condition.     

Autonomic regulation of the cardiovascular system in patients with chronic cholecystitis and hepatitis

Three hepatic porphyrias--acute intermittent porphyria, hereditary coproporphyria and variegate porphyria--are characterized by episodic acute attacks that consist of various neuro-psychiatric symptoms and signs, such as abdominal pain, vomiting, constipation, hypertension and tachycardia associated with increased excretion of porphyrins and porphyrin precursors. Peripheral neuropathy is manifested as pain in the extremities, and it may progress to a severe motor neuropathy. Measurement of porphobilinogen in the urine gives a prompt diagnosis during acute attacks. Attacks are often induced by precipitating factors such as drugs, alcohol, infection, fasting or changes in sex-hormone balance, and they should be eliminated when a patient is treated during an attack. Heme, the end biosynthetic product, is the most effective therapy for restoration of porphyrin biosynthesis to normal, and it is usually infused at 3 mg/kg daily for 4 days. Adequate calories are necessary and parenteral nutrition with carbohydrates may be necessary. Attacks may also require therapy for hypertension, pain and epileptic seizures. Strict avoidance of all precipitating factors may not be necessary in the asymptomatic phase.     

Sex hormones and headache

A variety of evidence suggests a link between migraine and the female sex hormones. Women with migraine outnumber men by at least a 2:1 ratio and definite patterns of development and attacks are noted at menarche and throughout the period of menses, related to trimester of pregnancy, and again at menopause, although it may also regress. Hormonal replacement with estrogen can exacerbate migraine; oral contraceptives can change the character and frequency of migraine headache. This article will cover approaches to the therapy of hormone-related headaches associated with the menstrual cycle, menopause, and oral contraceptives.     

Light-induced discomfort and pain in migraine

Quantitative thresholds for discomfort and pain with monocular and binocular light stimuli were measured in 67 controls and 67 migraine patients (37 migraine with aura and 30 migraine without aura). Patients were more photophobic during attack than outside attack (p < 0.03), and they were more sensitive to light than controls even between attacks (p < or = 0.0001). We found no differences in light sensitivity between migraine with aura and migraine without aura (p > or = 0.93). Unilateral pain affected light sensitivity on both sides. When asked with a questionnaire, 74% of patients answered that they were sensitive to light outside attack and 100% were sensitive during attack. Pain thresholds were generally lower among sensitive than non-sensitive patients (p = 0.004), indicating some agreement between subjective opinion and objective measurements of photophobia. Photophobia seems to be an intrinsic property of migraineurs. It is increased by migraine pain, but seems to be unrelated to migraine characteristics such as nausea, severity of attacks, pain character and pain laterality.     

Parental reports of seasonal mood and behavior changes in children

This paper reviews the therapeutics of migraine in the context of the clinical problem and its prevalence. General principles of pharmacotherapy for symptomatic and preventive medications are provided. Two new drugs, sumatriptan (recommended for acute symptomatic therapy), and valproic acid (recommended for migraine prevention), are reviewed. The clinical effectiveness and the mechanisms of action of these drugs are discussed.