Headache constitutes a frequent childhood complaint, yet published reviews of the subject almost exclusively concern adults. This review will discuss basic mechanisms of headache production and correlate these mechanisms with clinical symptoms. Causes of head pain, as well as suggested diagnostic investigations and medical management, are also described.
Only a limited number of structures residing within the cranium can give rise to painful sensations when stretched, dilated, or electrically stimulated.1 These tissues include the venous sinuses, the basilar aspects of the durai membrane, the meningea! arteries, and the cerebral arteries at their points of origin. In contrast, the meningeal coverings of the cerebral and cerebellar hemispheres - as well as the underlying brain substance, nutrient arteries, and veins - are insensitive to pain. Extracranial pain-sensitive structures include the scalp, muscular compartments, and associated blood vessels, in addition to joints and periosteum of the skull.
Both superficial (extracranial) and deep (intracranial) tissues of the head are innervated by components of the same sensory nerves.1 All painsensitive structures above the tentorium cerebelli, whether intra- or extracranial, are supplied by the fibers of the trigeminal (fifth) nerve, while cranial nerves 9 through 12 and the upper three cervical nerves serve the infratentorial region. Pain originating from intracranial sources is projected or referred superficially to regions that are homologous to the deep pain-sensitive structures. For example, painful stimuli arising in the floor of the right anterior cranial fossa are appreciated as an unpleasant sensation above and lateral to the right eye. This phenomenon of referred pain is thus useful in the localization of intracranial pathologic conditions.
CLASSIFICATION OF HEADACHES
CLINICAL CLASSIFICATION OF HEADACHES
Table 1 lists the most common causes of headaches in children, grouped under four broad categories. The classification is a modification of that drafted by the National Institute of Neurological Diseases and Blindness, NIH, Bethesda, Maryland.2
HEADACHE DUE TO CRANIAL INFLAMMATION
Meningeal irritation results from the entry of infectious organisms, chemical agents and drugs, or blood into the subarachnoid space. Spontaneous headache results because inflammation lowers the threshold of pain receptors located in the meninges and their associated blood vessels.1 The heightened pain sensitivity also accounts for the opisthotonos, nuchal rigidity, and pain produced by passive stretching of the meningeal membranes (Kernig's and Brudzinski's signs).
In bacterial meningitis, headache accompanies fever, lethargy or stupor, emesis, and convulsions. Head pain alone, however, is the complaint in 16 per cent of affected children.3 The headache of meningitis is moderately intense, constant, and nonthrobbing. It is bilateral and usually diffuse. It may be concentrated in the occipital and cervical regions, when inflammation is especially prominent in the basilar meninges. Because recumbency usually affords partial relief, the patient lies quietly and prefers not to be disturbed. Similar complaints are described for leukemic meningitis, but in this instance the meninges are infiltrated by malignant cells rather than being inflamed.4
Many substances introduced iatrogenically into the ventricular and lumbar fluid spaces provoke an inflammatory response in the meninges, giving rise to clinical manifestations of "chemical" meningitis. Inrrathecally administered diagnostic agents and drugs include radiographic contrast media, radioactive isotopes, air (in pneumoencephalography), dyes, chemotherapeutic agents, antibiotics, and steroids.5 Although some of these chemicals and drugs are themselves innocuous, preservatives (usually benzyl alcohol and benzoic acid derivatives) contained in the drug diluents can produce neurotoxicity.6 Symptoms resemble those of infectious meningitis and usually begin within 24 to 48 hours of cerebrospinal fluid instillation. Treatment is symptom oriented and should be continued until the meningeal reaction has subsided.
Spontaneous hemorrhage into the craniospinal subarachrtoid space is invariably associated with headache. Causes of subarachnoid bleeding in children include ruptured vascular anomalies and aneurysms, malignant hypertension, and major blood dyscrasias (hemophilia and thrombocytopenia).7 When significant bleeding occurs acutely, headache appears suddenly and is extremely painful. In most cases, pain is initially localized to the side of the source of bleeding. Hours later, the headache becomes less intense but more diffuse, and is accompanied by nuchal rigidity as hemoglobin breakdown products accumulate and incite a meningeal reaction. Alterations in consciousness and focal neurologic deficits often coexist with the headache.
Primary inflammatory diseases of the cranial arteries and veins are rare in children, primarily because of the virtual absence of temporal arteritis as a clinical entity in this age group. Intracranial arterial inflammation with associated thrombosis occasionally occurs secondary to systemic autoimmune disease (lupus erythematosis) or to subacute bacterial endocarditis. Neurologic abnormalities universally accompany the headache in these conditions. Intracranial phlebitis in children usually reflects chronic middle-ear infection and mastoiditis.
Localized or generalized increased intracranial pressure is the common denominator of headache-producing lesions in this category. Neoplasms, abscesses, and hematomas, the most common structural abnormalities producing traction headache, stretch or distort pain- sensi ti ve intracranial vessels and components of the durai membrane.
Most brain tumors in children are situated in the posterior fossa.8 Midline cerebellar tumors and ventricular neoplasms obstruct the normal flow of cerebrospinal fluid, producing hydrocephalus and its associated headache. Pain is bifrontal or diffuse and dull. The headaches typically begin in the early morning hours and may arouse the patient from sleep, building in intensity until vomiting supervenes, often without antecedent nausea. Pain may then subside, only to reappear the following day. As hydrocephalus increases, the headaches become continuous, improving only slightly with recumbency. Papilledema can usually be observed on funduscopic examination.
Other neoplasms in the posterior fossa can originate either in a cerebellar hemisphere or in the brain stem. These lesions do not cause hydrocephalus early and are usually discovered because of the neurologic deficits they produce. Headache, usually a minor symptom, is typically occipital in distribution.
Tumors located in the cerebral hemispheres produce headache by localized traction, since hydrocephalus is rarely a complication of cortical neoplasms. The pain is dull and nonthrobbing and may be restricted to the side of the underlying mass lesion. Diurnal variations occur, but changes in position have minimal beneficial effect. Vomiting is frequent. As the tumor becomes larger, the elevated pressure becomes widely distributed within the cranium, leading to generalized headache. Concurrent symptoms include seizure and cortical sensory or motor neurologic dysfunction.
Brain abscesses, like cerebral hemispheric tumors, cause pain by localized traction. Headache, usually overlying the lesion and often associated with percussion tenderness, is a common complaint. The history is important, because 50 per cent of all brain abscesses occur in children with cyanotic congenital heart disease, although they are rarely observed in infants under two years of age.9 Other important sources of abscess formation are externally contaminated skull fractures and infected structures adjacent to the cranial cavity.
As previously mentioned, hydrocephalus itself can induce headache. Similarly, any condition leading to a generalized elevation in intracranial pressure ultimately results in head pain. Included in this category are cerebral edema and pseudotumor cerebri, both with diverse causes (Table 2). The pathophysiologjc mechanisms of headache in these three disorders, probably identical, consist of widespread distortion of pain -sensi ti ve leptomeningeal vessels and durai structures.1
HEADACHE DUETO DISEASES OF CONTIGUOUS STRUCTURES
Diseases arising outside the cranial cavity can be responsible for headache symptoms.10 The most common are paranasal sinus inflammation and ocular defects. Infectious or allergic sinusitis characteristically produces periorbital pain, which is accompanied by fever, nasal congestion, and rhinorrhea. Eye strain, brought about by increased extraocular muscle tension, is seen in children with severe refractive error, astigmatism, and strabismus. The associated frontal or retroorbital headache is related to reading and scholastic activities.
CAUSES OF INTRACRANIAL HYPERTENSION
Dental malocclusion can cause bilateral headache by producing strain on the temporalis muscles. This disorder (Costen's syndrome) is frequently associated with upper molar disease and temporomandibular joint instability, represented by an audible and palpable jaw "click" during mastication.
Recurrent attacks of head pain that vary in intensity, frequency, and duration, and occur in the absence of systemic disease, are usually vascular. Pathophysiologic mechanisms producing vascular headache consist of an initial phase of intra- or extracranial vasoconstriction, followed by a longer interval of vasodilatation.1-11 The cause of the vascular changes is unknown. Experimental investigations suggest a relative instability of central nervous system vasomotor centers or an intrinsic vascular disturbance brought about by local alterations in the vasoactive hormones serotonin and norepinephrine .12,13 Concomitant with the vasodilatation, a localized extracranial vascular and perivascular tissue reaction occurs in the form of inflammation, edema, and the accumulation of toxic metabolites. 14 Muscular spasm or contraction also may result.
The clinical symptoms of "classic" migraine reflect neuropathologic alterations.11'15 Generally, a prodrome or aura, consisting of an autonomie and somatosensory or somatomotor disturbance, results from the intracranial vasoconstriction and partial cerebral ischemia. Autonomie dysfunction produces a constellation of complaints, which include anorexia, irritability, nausea, restlessness, and fluid retention. The most common somatosensory disturbance is visual and consists of either scotomas or field deficits. Typically, the visual loss is slow, and several minutes may elapse before the phenomenon is complete. Vascular alterations in the branches of the contralateral posterior cerebral artery probably account for the visual disturbance. Less frequent neurologic defects include hemisensory and hemiparetic abnormalities - such as tingling, weakness, or incoordination of a hand or foot - presumably the consequence of contralateral cortical ischemia secondary to anterior or middle cerebral artery spasm. Aphasia may appear when the dominant cerebral hemisphere is affected. In rare instances, brain- stem-mediated functional disturbances occur (vertigo, altered consciousness, ataxia, and dysarthria), resulting from basilar artery vasospasm.16
The migraine prodrome eventually blends with or is replaced by the headache phase. Pain is typically unilateral, well localized, and throbbing, reflecting increased pulse pressure in the afflicted extracranial vessels. It is rarely sudden in onset, instead building slowly in intensity to a peak some hours or, occasionally, days later. Photophobia may be a concurrent complaint. When the headache reaches its zenith, vomiting commonly results; this, in turn, partly or completely relieves the painful symptoms, culminating in relaxation and sleep. Examination during the headache phase may disclose dilated, tender temporal arteries, scalp discoloration and edema, and increased muscular tension. Pain is relieved instantly by compression of these arteries. As anticipated, the headache occurs ipsilateral to the antecedent intracranial vasomotor alterations and contralateral to the neurologic dysfunction.
"Classic" migraine generally begins in children between the ages of seven and 15. 17-18 However, there is often a history of epidosic functional disturbances that suggests a fragmentary migraine complex. Thus, retrospective questioning may reveal periodic attacks of isolated unilateral headache, abdominal pain and vomiting, or, less commonly, an overt and transient neurologic deficit. Furthermore, one could not expect a three-year-old child to describe, in detail, rather complex headache symptoms or scintillating scotomas. Family history is also important, since the incidence of migraine in parents of affected children is 50 per cent or more.15 One must be cautious, however, since headache is universal but migraine occurs in only 6 per cent of the population.19 Many parents consider their own headaches to be migrainous, although direct questioning most often discloses a different variety. The frequency of migraine in schoolchildren is approximately 2.5 per cent in the seven-to-nine-year age group, increasing to 5 per cent in the 13-to-15-year age group.17
Migraine need not always be "classic." Other forms include "common" migraine, in which the prodrome is less striking or even absent and the headache less typical - i.e. , bilateral, nonthrobbing, and without associated emesis. "Common" migraine (undifferentiated vascular headache) is probably commonplace in older children and adolescents. Presumably, such headaches reflect extracranial vascular disturbances without antecedent intracranial vasospasm.
"Cluster" (Horton) headache is localized vascular headache accompanied by ipsilateral lacrimation, conjunctival congestion, nasal congestion, and rhinorrhea.20 Episodes are brief and occur in closely packed groups (dusters) separated by long remissions. These headaches are rarely seen in children and typically occur in men between the ages of 20 and 40. In children, such autonomie disturbances may reflect underlying cerebrovascular pathology.21
Two well-described clinical entities known to occur in children include "hemiplegie" migraine and "ophthalmoplegic" migraine.22,23 With hemiplegie migraine the patient experiences unilateral upper- or lower-extremity weakness with loss of manual dexterity. Facial weakness may be present and is of the central (upper motor neuron) type. With ophthalmoplegic migraine the deficit is limited to one eye and consists ofptosis, pupillary dilation (relative to the contralateral pupil), and medial rectus weakness resulting in exotropia. The ocular abnormalities, which may occur alone or in combination, reflect a functional disturbance of the oculomotor (third) nerve, presumably of vascular origin. Other cranial nerves may be involved as well. Both the "hemiplegie" and "ophthalmoplegic" syndromes differ from "classic" migraine in two important respects: (1) headache may be minimal or absent, and (2) the neurologic deficit may be prolonged, lasting days or even weeks. Often such patients are subjected to angiography to rule out intracranial structural disease, usually with negative results.
NONMIGRAINOUS VASCULAR HEADACHE
Headache can occur in conjunction with a variety of systemic illnesses. The common substrate is vascular dilatation (intra- or exrracranial), induced either by reflex mechanisms or by direct action of a vasotonic agent. Disorders include any febrile infection, systemic hypoxia, cerebral ischemia, hypoglycemia, respiratory acidosis (hypercapnia), hypertension, seizures, and head trauma (concussion). Chemical agents and drugs, such as nitrites, produce direct vasodilatation, often with resultant headache.
In most instances of nonmigrainous vascular headache, a thorough medical history and physical examination (including vital signs) will uncover the true nature of the ailment, since headache is usually only one aspect of a larger spectrum of symptoms. The headache itself, being vascular in origin, may simulate migraine attacks. Prodromes of neurologic deficit are usually absent, however, or, if present, generally reflect bilateral cerebral dysfunction, as in metabolic encephalopathy. Treatment is directed to the resolution or control of the underlying disease process, which usually suffices to relieve the headaches.
MUSCLE CONTRACTION HEADACHE
Perhaps the most frequent cause of headache is muscle tension.24 Sustained contraction or spasm of the muscles of the scalp and neck occurs, with subsequent production of chronic, frequently persistent pain. The headache is either bandlike in distribution or limited to affected muscles in the frontal, occipital, or posterior cervical regions. Pain is typically bilateral, dull, and nonthrobbing, and is often described as a sensation of tightness, pressure, or constriction. Physical examination reveals visible skin furrows overlying the affected muscles, along with focal tenderness and induration. Headaches typically begin at school or work and disappear during weekends and vacations. Muscle contraction headaches in children are extremely common and, as in adults, usually signal psychologic stress.2,5
Most patients, including children, who come to the physician with complaints of headache require little more than a detailed medical history and physical examination. In this regard, it is the physician's primary function to differentiate chronic, relapsing vascular (tension) headache from head pain that reflects underlying intra- or extracranial structural disease or systemic illness. Pertinent historical data include a review of the headache symptom itself, with reference to its frequency, time of onset, duration, character, location, response to drugs, and presence or absence of a prodrome and associated symptoms, including neurologic defects. Other important aspects of the medical history are past illnesses, physical and mental development, nutritional status and familial disorders, such as metabolic disease, neoplasia, epilepsy, and migraine. Insight into the child's personality, family and peer relationships, and school performance may offer significant clues to the pathogenesis of the headaches. Physical examination must include systematic neurologic testing of higher integrative functions, the cranial nerves, and sensory, motor, reflex, and cerebellar systems.
Specific laboratory studies are reserved for those children whose headaches suggest local structural or systemic disease. Base-line neurologic procedures include skull x-rays, electroencephalograms, echoencephalograms, and brain scans; all these are noninvasive tests. When available, computerized transaxial tomography has become an indispensable neurodiagnostic tool.26 Early lumbar puncture should be performed only when meningitis or subarachnoid hemorrhage is suspected. Intracranial angiography and pneumoencephalography are best accomplished after neurologic or neurosurgical consultation. Metabolic investigations should be ordered as indicated.
Electroencephalography may be of value in the differential diagnosis of vascular and muscle tension headache. In 50 per cent of children with migraine, the EEG is abnormal when performed during pain-free intervals.27 Findings include symmetric slow-wave activity, 4-6-cycleper-second paroxysmal hyperactivity, and, occasionally, spike discharges. Focal abnormalities are uncommon, but are frequently observed if the tracing is obtained during the headache attack.15 Spikewave complexes, indicative of a convulsive disorder, are rarely recorded.
TREATMENT OF HEADACHE SYMPTOMS (TABLE 3)
Acetylsalicylic acid remains the preferred drug for head pain of any origin and is particularly useful in muscle contraction and nonmigrainous vascular headaches.28-29 Acetaminophen appears to be equivalent to acetylsalicylic acid in its analgesic effect, although reduced antiinflammatory action makes it less useful in headaches having a vascular-inflammatory component.30 In appropriate doses these two drugs are as effective as other nonnarcotic analgesics and many narcotic derivatives as well.28,1*33 Because of erratic absorption, suppository forms must be used in higher doses than for agents given via the oral route.
Sedation is often helpful in patients with muscle tension and vascular headaches.29 Safe and appropriate sedatives in young children consist of a small group of antihistamines whose action is also antiemetic. Cyclizine and promethazine are suggested drugs of choice in this category. Diazepam and chloral hydrate can be employed as stronger sedatives, the former having the additional specific action of muscle relaxation. Barbiturates should be avoided in young children, as they may produce paradoxic hyperactivity.
In the treatment of severe, intractable headache secondary to cancer, subarachnoid hemorrhage, and meningeal or vascular inflammation, more potent analgesia and sedation are often necessary. The drug of choice for severe pain is morphine.34 This drug is effective subcutaneously, but must be used with caution, since it can induce vomiting, an associated problem in some children. Meperidine and methadone are satisfactory alternatives, as both can be administered orally. These medications can depress respiration and, therefore, must be used sparingly in patients with intracranial hypertension in whom pulmonary ventilation may already be compromised.
Drugs to control nausea and vomiting include the antihistamines and phenothiazines.35 Cyclizine and promethazine act directly on the emetic center in the floor of the fourth ventricle, whereas chlorpromazine and its derivatives act on the more caudally located chemoreceptor trigger zone.35 Considering these different pharmacologie effects, the use of cyclizine or promethazine is recommended. The known extrapyramidal side effects produced by phenothiazines are essentially avoided.
Ergotamine, a direct vasoconstrictor, remains the drug of choice for migraine headaches.1,29 Adult dosage is 1-2 mg. every half-hour orally or sublingually until relief is obtained. No more than 6 mg. should be consumed per attack, however, nor more than 10 mg. weekly. Chronic, indiscriminate usage leads to "ergotism" with manifestations of peripheral circulatory insufficiency. Injectable forms of ergotamine can be used efficaciously in patients who are vomiting or are otherwise unable to take medication orally. Dosage is 0.25-0.5 mg. initially, with repeated injections in 30-60 minutes if necessary. Ergotamine can be safely supplemented with analgesics, sedatives, and antiemetic agents. Its use is generally recommended for children over eight years and for adolescents, although there is no apparent contraindication to its administration in younger children. However, tablets containing less than 1 mg. or elixirs are not available.
DRUG THERAPY FOR HEADACHES
Methysurgide (Sanserf*), an inhibitor of serotonin, has been employed successfully as prophylaxis for migraine headache in adults. Because of its capacity to induce fibroproliferative changes in the retroperitoneal and pleural spaces, methysurgide has not been recommended for use in children.30
Propranolol, a beta-adrenergic blocker, may act to prevent the vasodilatation stage of migraine headache. The success of such prophylaxis has been equivocal in adults,28 although a preliminary report in children suggests that this drug may be useful to reduce the severity and frequency of migraine attacks.37 More definitive studies are required before the full usefulness of propranolol will be known.
As in all areas of medicine, the use of a few clearly understood medications is better than the use of numerous questionably efficacious ones of uncertain safety.
1. Datessio, DJ. Wolff s Headache and Other Head Pain. New York: Oxford University Press, 1972.
2. Ad Hoc Committee on Classification of Headache; Special report. Arch. Neuroi. 6 (1962). 173-176.
3. Smith. D.H., et al. Bacterial meningitis: A symposium. Pediatrics 52 (1973), 586-600.
4. Haghbin, M., and Zuelzer, W.W. A long-term study of cerebrospinal leukemia. J. Pediatr. 67 (1965). 23-28.
5. Fishman, R.A. Cerebrospinal fluid. In Baker. A.B.. and Baker, LH. (eds.). Clinical Neurology (I). New York: Harper & Row, 1973.
6. Saiki, J. H., et al. Paraplegia following intrathecal chemotherapy. Cancer 29 (1972). 370-374.
7. Bray, P.P. Neurology in Pediatrics. Chicago: Year Book. 1969.
8. Matson, D.D. Neurosurgery in Infancy and Childhood. Springfield, III.: Charles C Thomas. Publisher. 1969. pp. 403-522.
9. Clark, D.B. Brain abscess and congenital heart disease. Clin. Neurosurg. 14 (1966), 274-287.
10. Heyck, H. Examination and differential diagnosis of headaches. In Vinken, P.O.. and Bruyn. G.W. (eds.). Handbook of Clinical Neurology (V), New York: John Wiley & Sons. 1968.
11. Friedman, A.P. Migraine headache. J.A.M.A. 222 (1972), 1399-1402.
12. Dalessio, DJ, On migraine headache: Serotonin and serotonin antagonism. J.A.M.A. 181 (1962), 318-321.
13. Lance. J.W., Anthony. M., and Hinterberger, H. The control of cranial arteries by humoral mechanisms and its relation to the migraine syndrome. Headache 7 (1967). 93-103.
14. Chapman. L.F., et al. Neurokinin. a polypeptide formed during neuronal activity in man. Trans. Am. Neural. Assoc. 85 (1960), 42-45.
15. Friedman, A.P. Migraine (pathophysiotogy and pathogenesis). In Vinken, P.J., and Bruyn. G.W. (eds.). Handbook of Clinical Neurology (V). New York: John Wiley & Sons, 1968.
16. Bickerstaff, E.R. Basilar artery migraine. Lancef 1 (1961). 15-17.
17. Bilie. B. Migraine in school children. Acta Paediatr. Scand. 51 (Suppl. 136, 1962). 1-151.
18. Burke, E.G.. and Peters. G.A. Migraine in children: A preliminary report. Amer. J. Dis. Child. 92 (1956). 330-336.
19. Lennox. W.G., and Lennox, M.A. Epilepsy and Related Disorders. Boston: Little. Brown and Company, 1960.
20. Duvoisin, R.C. The cluster headache. J.A.M.A. 222(1972), 1403-1406.
21. Vannucci. R.C., Solomon, G.E., and Deck. M. D. F. Cerebral arterial occlusion and cluster headaches in neurofibromatosis. Amer. J. Dis. Child. 727(1974), 422-424.
22. Ford, F.R. Diseases of the Nervous System in Infancy, Childhood and Adolescence. Springfield. III.: Charles C Thomas, Publisher, 1966. pp. 1179-1189.
23. Verrei, S., and Steele, J.C. Alternating hemiplegia in childhood: A report of eight patients with complicated migraine beginning in infancy. Pediatrics 47 (1971), 675-680.
24. Blumenthal, L.S. Tension headache. In Vinken, P.J., and Bruyn. G.W. (eds.). Handbook of Clinical Neurology (V). New York; John Wiley & Sons, 1968.
25. Apley, J. The Child With Abdominal Pains. Oxford. England; Biackwell Scientific, 1964.
26. Gawler, J., et al. Computer-assisted tomography (EMI scanner). Lancet 2 (1974), 413-423.
27. Froelich, W.A.. et al. Headache in childhood: Electroencephalographic evaluation of 500 cases, Neurology 10 (1960), 639-642.
28. Moertel, G.G., et al. A comparative evaluation of marketed analgesic drugs. N. Engl. J. Med. 286 (1972), 813-1815.
29. Friedman, A. Reflections on the treatment of headache. Headache 11 (1972), 148-155.
30. Acetaminophen, valadol and analgesic renal injury. Med. Lett. Drugs Ther. 13 (1971). 74-76.
31. Darvon and Darvon-N. Med. Lett. Drugs. Ther. 14 (1972), 37-38.
32. Percodan. Med. Lett. Drugs. Ther. 14 (1972), 44.
33. Pentazocme. Med. Lett. Drugs Ther. 14 (1972), 46-47.
34. The choice and dosage of narcotic analgesics. Med. Lett. Drugs Ther. 15 (1973), 32.
35. Cockel, R. Anti-emetics. Practitioner 206 (1971). 56-63.
36. Friedman, A.P. Headaches and migraine. In Getlis, S., and Kagan. B. (eds.). Current Pediatrie Therapy (Vl). Philadelphia. W.B. Saunders and Company, 1973.
37. Luduigsson, J. Propranolol in the treatment of migraine in children. Lance/ 2 (1973), 799.
CLASSIFICATION OF HEADACHES
CAUSES OF INTRACRANIAL HYPERTENSION
DRUG THERAPY FOR HEADACHES