The migraine syndrome is a pattern of dysfunction integrated within the central nervous system and manifested as widespread bodily disturbances, both non-painful and painful. The outstanding feature is periodic headache, usually unilateral in onset but at times becoming bilateral or generalized. The attacks may vary in duration from a few minutes to several days and, in severity, from trifling symptoms to prolonged disabling illness. The headaches are associated with “irritability,” nausea, and often photophobia, vomiting, constipation, or diarrhea. Although most common in the temple, headaches may be experienced anywhere in the head, face, and neck. The syndrome runs in families.
For a period of several hours to several days preceding the headache, the cranial arteries undergo a variable contractile state indicated by a facial flushing or pallor and by other transient cranial vasomotor phenomena such as vertigo. In the hour preceding the headache, a variety of visual and other neurologic abnormalities due to transient local constriction of cerebral or retinal arteries occur in about 10 to 15 percent of the instances.
TheSe prodromes may take the form of scintillating scotomas, visual field defects such as unilateral or homonymous hemianopsia, and, occasionally, hemiplegia. More sustained neurologic defects and even cerebral infarction have rarely occurred. As the vasoconstrictor phenomena recede, vasodilator headache commences, sometimes overlapping, sometimes beginning after a short symptom-free interval. The pain is throbbing and aching, is appreciably reduced by pressure on the common carotid and the affected superficial artery, and is characteristically eliminated or reduced by vasoconstrictor agents, particularly ergotamine tartrate.
The walls of the dilated cranial arteries and the adjacent tissues become edematous and tender. With sustained vasodilatation for several hours, the easily compressible arteries become rigid and relatively noncompressible, and the pulsatile pain becomes a steady ache. Redness and swelling of the eye with excessive tearing, and redness and swelling of the nasal mucosa with or without epistaxis, may occur along with the headache. A secondary muscle contraction component of the headache may outlast the vascular pain and will not be modified by vasoconstrictor agents.
One variety of headache closely related to migraine syndrome is the cluster headache. This head pain affects men much more than women, usually beginning between the third and sixth decade. Attacks come on abruptly with intense throbbing pain arising high in the nostril and spreading to involve the region behind the homolateral eye and sometimes the forehead as well. During the attacks, which last up to two hours, seldom more, the nose and eye water. The skin reddens and a homolateral Horner’s syndrome with pupillary constriction and ptosis may develop. The attacks tend to occur from once to several times daily, in clusters lasting weeks or, less often, months.
Without apparent reason, the cluster subsides as suddenly as it began, and the patient commonly remains free of headache for weeks or months until another cluster begins. During a cluster period, but not between, alcohol is likely to induce attacks. When headaches recur in close succession, the Horner’s syndrome may outlast the headache.
Pathogenesis of Migraine Headache.
Before the onset of migraine headache a generalized accumulation of fluid may occur as part of a nonspecific disturbance in fluid and electrolytes that is found in many persons with and without the migraine syndrome during periods of stress. There is evidence of a general abnormality of vascular behavior in many migraine subjects, and the extracranial vessels of such subjects show more variability in their contractile patterns than those of normal subjects even during headache-free periods. Sym-pathetic nerve stimulation or section has little effect on these vessels or on the migraine attack, and humoral agents have long been sought as the basis of the migraine syndrome.
Local fluid collected from sites of swelling at the point of maximal headache and tenderness during an attack contains a vasodilatory polypeptide of the bradykinin type that lowers pain thresholds and may be a factor in a local sterile inflammation. However, neither kinins, histamine, nor substances such as acetylcholine satisfactorily explain the generalized manifestations of the disorder. Several lines of evidence suggest that abnormalities in the metabolism of serotonin may play a role in the migraine syndrome.
Reserpine, which induces a drop in serum serotonin levels, will often induce a migraine attack, and serum levels of serotonin have been found to drop spontaneously just before migraine attacks. During migraine attacks, an increased quantity of serotonin metabolites has been found in the urine. Methysergide, a powerful serotonin antagonist, prevents or reduces the frequency of migraine attacks in most subjects. How methysergide works is unclear. D’Alessio et al. suggested that it acts centrally on the brain to modify vasomotor regulation and peripherally to potentiate the vasoconstrictive responses of the cranial blood vessels to catecholamines. Curran and co-workers speculate that methysergide is a competitive antagonist to serotonin, occupying similar receptor sites in pain-sensitive vessels.
Management of Migraine Syndrome.
Headaches of low intensity are usually eliminated by 0 3 to 0.6 gram of aspirin, but sometimes require 60 mg. of codeine phosphate as well.For severe vascular headache, the restoration of the painfully dilated vessels to a nonpainful constricted state and the restoration of pain threshold to normal are accomplished best by the intramuscular administration of 0.25 to 0.5 mg. of ergotamine tartrate, not to exceed 0.5 mg. in any one week. If the agent is administered in amounts of 1.0 to 2.0 mg. by suppository, the side effects of nausea, vomiting, and elevated blood pressure are diminished. Ergotamine tartrate may also be given by mouth in 3.0 mg. amounts, to be swallowed or absorbed sublingually. This first dose may be repeated in 30 minutes, and a third given in another 30 minutes if the headache persists. Ergotamine tartrate, 1 mg., can also be given in tablets in combination with caffeine, 100 mg., up to 8 tablets for any single headache attack. The amount of ergotamine so administered should not exceed 10 mg. in any one week. Administration by mouth or by suppository is less predictably effective than intramuscular administration.
What Is The Prevention of Migraine Syndrome.
Of utmost importance in the prevention of attacks is a consideration of the personal problems of the patient. Patients with migraine headaches are anxious, striving, perfectionistic, order-loving, rigid persons who, during periods of threat or conflict, become progressively more tense, resentful, and fatigued. The person with migraine often attempts to gain approval by doing more and better than his fellows and to gain security by holding to a stable environment given system of excellent performance, even an n high cost of energy.
This pattern brings increased| responsibility and admiration, but little love. aSl that he feels greater and greater resentment at ism. pace he feels obliged to maintain. Then tensile associated with repeated frustration, sustained resentment and anxiety, often followed by fatigue and prostration, become the setting in which the migraine attack occurs. Treatment is best if it allows the patient free and repeated expression of his conflicts, resentments, and dissatisfactions, enables him to recognize the nature of his dilemma and its relationship to the physiologic basis of his pain, guides him toward accepting a more realistic appraisal of his needs, and establishes a more efficient regimen compatible with his individual equipment. About two of three patients can be appreciably helped by such aid.
For patients in whom attention to psychological attitudes and adjustment of life situations fail to bring significant relief, two forms of long-term pharmacotherapy have been useful. One is the monoamine oxidase inhibitor phenelzine sulfate, 45 mg. daily, which induces a significant reduction in headache frequency in most patients with migraine, and can be given indefinitely. The other is the serotonin antagonist methysergide, which in doses of 2 mg. three to four times daily is effective in about two of three cases in preventing headache of the migraine type. However, methysergide must be used with great caution.
Both ergotamine tartrate and methysergide possess the ability to induce profound vasoconstriction and are contraindicated in pregnancy, peripheral vascular disturbance, severe- hypertension, coronary artery disease, thrombophlebitis, and renal disease. Serious and unexpected vasospastic and psychic reactions have occasionally occurred with methysergide. Retroperitoneal fibrosis producing back pain and ureteral obstruction has been reported. Any of these serious complications necessitate prompt discontinuance of methysergide, and any single course of the drug should not outlast three months.