Clinical Approach to Headache in Children and Preventive Therapy of Migraine

Transcription

1 CLINICAL MEDICINE JIACM 2005; 6(1): Clinical Approach to Headache in Children and Preventive Therapy of Migraine KK Sinha* Headache is an ancient disorder and has been well described in literature from the earliest time. All physicians who do take care of children, know that headache is the most common neurological disorder after epilepsy in children. One population-based study estimated that 90% of men and 95% of women had unprovoked headache annually 1, and according to another study 10% of children between age 5 to 15 have migraine, and about 1% have chronic tension headache 2. Even non-organic headache can be a major problem as it may result in missing school days and lead to severe interruption in learning and education. If the headache is chronic, it might lead to developmental regression, depression, other behavioural problems, and can severely affect a child s daily day activities and future life. But most parents want medical attention for a child with headache, not so much for relief of pain as wanting to know if the child has a serious disease of the head such as a brain tumour or meningitis. And if this is the purpose, the prime objective is to assure the parents that the headache in a given child is not a symptom of a major intracranial illness, because all headache do not necessarily mean an underlying serious structural disease of the brain. Every headache in a child may not be explained, but evaluation of a child s headache is important in order to arrive at the proper diagnosis and, if necessary, start appropriate treatment. Headache has been classified in different ways over the years, but in children what one usually encounters is a migraine-like headache, or a chronic tension-type headache (chronic, non-progressive headache). Most neurologists however, have the fear that they are going to miss headache that heralds some serious disease. Why one gets headache is not entirely clear, because the brain itself is insensitive to pain and it can be said that brain does not cry. The reason for headache is the sensitivity to painful stimuli of extracerebral structures such as the blood vessels and the meninges; structures that are supplied by fifth, ninth, and tenth cranial nerves. It is usually possible, often by history and physical examination alone, to differentiate headache that is only pain problems from those that are serious and may need various diagnostic tests. The proper evaluation of the headache patient begins with a carefully taken history, general examination, and a thorough neurological examination. Once the history and physical examination are over, the physician should formulate a differential diagnosis particularly focussing on the most likely aetiology and the severity of the illness. If an organic aetiology is suspected, appropriate diagnostic tests may be necessary to confirm the diagnosis and exclude serious or life-threatening causes. Most children with headache will also need monitoring the subsequent clinical course of the illness, to make sure that: (i) the initial diagnosis was correct; (ii) the child does not have any other illness to account for his headache; (iii) the treatment suggested was appropriate, effective, and free from adverse effects. History taking in a child with headache History is the most important part in the evaluation of headache to determine the correct diagnosis. When a child with headache comes in the examination room of the physician, it is advisable that he begins talking to the child asking him questions that would help him in the diagnosis. These questions need to be addressed to the child rather than to the parents. Children are little adults and can provide very useful information, if questions are asked appropriately. Even young children may give a good description of many characteristics of their headache; although it is important to realise that younger the child, less specific will be his response. Children of different ages also respond to pain differently. Whereas younger children * Neurologist, Mansarovar, Booty Road, Bariatu, Ranchi , Jharkhand.

2 react to pain by crying and rocking their head if headache is severe, older children may simply complain of severe headache and close their eyes. An older child or adolescent can also describe the pain better and localise it well. The physician may ask the questions in any way he wants, but one suggested order is the following 3-6 : a. Does the child have one or more than one type of headache? Because some patients may have more than one type of headache, it is important to find out the different types of headache the patient has, and inquiry should be made about each type separately. This may be done by asking the patient whether all headache are similar or whether they vary in type and severity. We all have experience of patients who have a mild headache almost every day with superimposed more severe headache which is often associated with nausea, vomiting, vertigo, photophobia, and phonophobia. b. When and how did the headache start? While many patients are vague about the onset of their headache, some can easily recall their first headache and can also describe the factors that started it. Such features might be physical such as a head trauma or even an emotionally stressful situation. c. How long has the headache been going on? Many children or their parents can easily tell how long the headache has been present; whether for days, weeks, months or years. This is prognostically an important question. If the headache has been going on for a long time without ever giving rise to signs of raised intracranial pressure or progressive neurological decline, then obviously, it is unlikely to be serious in nature. Episodic migraine in children typically has its onset in the first decade, whereas the chronic non progressive daily headache (tension headache) usually appears after 10 years of age. To know the temporal pattern and course of headache, the next question is important. d. Is the headache intermittent, or progressive, or non-progressive? Whatever the headache type, one of the first things to be inquired about and to be identified is its temporal pattern. If the pattern suggests that the headache is intermittent and comes in attacks such as one, two, or more times in a month; and if it is also associated with nausea, vomiting, photophobia, or phonophobia, then migraine is the most likely diagnosis. On the other hand, if it is becoming more severe over time, and is also associated with the appearance of new neurological features, an organic cause should be strongly suspected. For example, in an older child with a tumour, the headache gradually increases over time, but this is not what one sees in a younger child, in whom the headache is often biphasic. Such younger children begin with bad headache that awaken them from sleep and then they vomit; but they begin to feel better as the day progresses and the headache then comes back in 2 to 3 days or more, and at this point, the suspicion of a brain tumour becomes much stronger. The reason for this biphasic headache is that in very young children the skull can expand by separation of sutures and therefore can accommodate the raised intracranial pressure for a sufficient length of time. The child with migraine has a temporal progression which follows quite a different pattern. As said earlier, they have headache that comes and goes with periods in which there is no headache at all. A headache-free period is necessary to make a diagnosis of migraine in a child. If the headache occurs daily or almost daily from the time the patient awakens until the time he or she goes to sleep, and if it has been present for 4 months to years, and if new neurologic features have not appeared, the diagnosis most likely is a chronic daily non-progressive headache (chronic tension-type headache, also called muscle contraction headache ). Here, headache is fairly consistent, although it may have undulations, and headache is present almost every day. Many-a-time, one sees a combination of migraine and tension headache; the so called mixed headache. Such children may tell that they have headache every day, but they have valleys of less severe headache with interspersed peaks of severe 24 Journal, Indian Academy of Clinical Medicine Vol. 6, No. 1 January-March, 2005

3 headache. These children with mixed headache with coincidental migraine and tension headache are often difficult to sort out. e. How frequent is each type of attack in a particular patient? The frequency of headache is often very helpful in the diagnosis. For example, migraine occurs in attacks about 2 to 4 times every month. Typical migraine does not occur daily, unless it gets converted into what is now called a transformed migraine pattern over the years. Cluster headache also typically occurs episodically in clusters of attacks, about 2 or 3 times every day for several months, then they might disappear for several months or even years. On the other hand, chronic, non-progressive headache (chronic, tension-type headache) occurs almost daily or five to seven times each week or atleast 215 days in a month. This might continue for months or years. The quality of headache is not very helpful in the diagnosis in younger children. One will rarely find a child who describes a pulsating quality of a migraine headache as one sees in adults. It is also important to see whether or not the frequency, or the pattern, or quality, of a particular type is changing. For example, intermittent relapsing headache might become more frequent with each attack, coming closer to the next and then might even become a daily headache, as happens when a typical intermittent migraine headache converts into a chronic, daily migraine. It is important that when one is dealing with headache in children, one has to ask the patient and the parents again and again, and go through the history again in subsequent interviews, because some points in the history and physical examination may not strike the patient, the parents, and the physician, at the first interview. This is also true for many other similarlooking repetitive neurological syndromes such as epilepsy. Change in the pattern of headache is important, but change in behaviour and school performance are equally important. These are very sensitive indicators of structural disease of the brain. However, one must watch children who are doing poorly in school and because of their substandard performance they are only acting out. Such headache has adolescence related adjustment problems and needs psychological evaluation and attention. But these may also sometimes indicate gradually developing serious problems which the parents did not take notice of initially; so it is important to remember that a combination of changes in behaviour and school performance and headache might suggest organic disease. f. How long does the headache attack last? The answer to this question could help make a diagnosis. For example, migraine in young children lasts from a few minutes to about 3 hours and only uncommonly for longer periods. On the other hand, migraine in an adolescent may last much longer and can also be more severe. Attacks of cluster headache do not usually last longer than 30 to 40 minutes, although they might come back in a few hours. Chronic, daily, non-progressive headache may last all day or several days. g. Does the headache occur in any special situation? Most children, adolescents, and parents are able to recognise specific situations, which cause headache. For example a car ride may sometimes, provoke a migraine attack; or, return to school on a monday morning or after a vacation or holiday, or domestic tension, or death of a friend or a dear one, may percipitate tension headache. However, a headache that awakens a child from sleep often heralds a serious problem. h. Is headache induced by certain specific food, medicine, or activity? There could be some patients who are able to identify specific food or medicine or environmental situations such as excessive heat or exertion or exposure to sun that induce headache. Headache that gets worse on straining during a bowel movement, usually suggests some important illnessas its cause, such as a raised Journal, Indian Academy of Clinical Medicine Vol. 6, No. 1 January-March,

4 intracranial pressure, or a vascular anomaly. i. Does the patient have warning symptoms? Some children can describe the prodrome that might herald their headache several minutes before the attack. They may get a warning signal that the headache may be coming on. And parents who are keen observers may notice that the child develops certain prodromal features such as he might become quiet, or his skin colour might change, or there is a change in his behaviour. j. Does the headache appear at a particular time of the day? The time of the day when the headache appears, is important. For example, if it occurs first thing in the morning, or if it wakes the child from sleep, or if it tends to occur in the afternoon. It is important here to find out if the headache wakes him up from sleep as it may eventually turn out to be a serious illness. Also, make sure that it is not the child who wants simply to stay in bed which usually means tension headache. k. What is the site of headache? Usually the localisation of headache is non-specific; sometimes, however, it can be diagnostically important. If the child always localises his pain on the same spot of the head and takes his pointed finger to exactly where his head hurts, the physician must pay attention. It might be hurting, because he may have an eroded bone from a dermoid or a brain tumour, or an arterio-venous malformation, or some other structural disease. Pain of otitis media or mastoiditis is frequently localised to the affected ear or a particular region around the ear. Pain of optic neuritis and glaucoma, or cluster headache, is located to one eye and the pain of temporomandibular arthritis is localised to the ipsilateral joint or infra-aural region. Migraine in the young is usually bifrontal or bitemporal, and the typical hemicranial headache seen in adults is not common in them; but it does become more frequent and more localised as they enter into adolescence. Pain of maxillary sinusitis is frequently located in the malar region, or above the eye, or below the eyes, or between the eyes. Sphenoidal sinusitis headache may be referred to the vertex. Pain in cluster headache is unilateral, usually either in the orbit or around it. In chronic paroxysmal hemicrania, headache is always unilateral and does not change sides as it might, in hemicrania of migraine. Headache due to muscle contraction is bifrontal or bitemporal, or has a band-like feeling encircling the head. Episodic occipital headache may be observed in basilar artery migraine, or occipital neuralgia, or craniocervical junction lesions. l. Are there other symptoms associated with headache? This is a very important question and needs to be asked to every patient. Gastrointestinal symptoms such as anorexia, nausea, vomiting, abdominal pain are frequent accompanying features of migraine. There may also be autonomic symptoms such as pallor, chills, flushing, fever, dizziness, syncope, or behavioural changes. Vertigo may also be a prominent accompanying feature of migraine headache. Temporary or permanent neurologic dysfunction such aphasia, hemiparesis, confusion, unilateral blindness, hemianopsia, ophthalmoplegia, or loss of consciousness are rare associated features of migraine; but if they are present, an organic aetiology must be sought. Questions regarding symptoms that might suggest raised intracranial pressure or a progressive neurological disease are asked at this point. For example, are symptoms such as lethargy or personality changes, nausea, vomiting, visual difficulties, focal signs or gait disturbance, gradual mental decline, and changing pattern of headache present? Or are there any symptoms that could specifically suggest raised intracranial pressure? m. What does the child do when he has a headache? This is also an important question and may give a clue to the diagnosis. If a migraine headache occurs when the child is in school, he may simply put his head on the desk or he may want to go home. In migraine attacks associated with nausea, vomiting, or vertigo, 26 Journal, Indian Academy of Clinical Medicine Vol. 6, No. 1 January-March, 2005

5 children want to go home and want to lie in a dark, quiet place with curtains drawn. With severe, chronic, non-progressive headache, children do not want to go to school and miss classes. n. What improves their headache? Most children in a severe migraine attack want to lie in bed quietly in the dark, or take a pain-killing tablet to treat their headache. Mothers may apply cold compresses, or give them a sleeping tablet which is many-a-time beneficial, but not always. Children and adolescents with chronic tension type headache do not usually find relief with any medicine, but often a sleeping tablet helps them. o. Is there anything that makes the headache worse? It is important to observe factors that make a headache worse. Patients with migraine try to avoid activities, movements, and exposure to sun, because these usually make their headache worse. In both chronic tension type headache and migraine, headache gets worse with bright light, noise, or strenuous activity. Cluster headache patients do not find relief even with rest in bed; they are often restless. Another question that needs to be asked is, whether the headache increases with any act that involves valsalva-like manoeuvre such as sneezing or straining at stool. If that is so, it often reflects increase in the intracranial pressure. Such children usually do not have simple tension-type headache; they may have something more serious that causes a rise in intracranial pressure. p. Do associated symptoms continue even when headache is gone? If associated symptoms continue even when the headache has disappeared, it usually means presence of an organic cause for headache such as raised intracranial pressure, or a mass lesion. When symptoms such as personality changes, forgetfulness, lethargy, visual problems, nausea, vomiting, and gait imbalance persist, physicians need to get alerted. q. Is there a history of headache in the family? Migraine is supposed to have a genetic basis, and it tends to occur in clusters in the family. It is important to ask if parents, siblings, or grandparents, or other first degree or second degree relatives have a history of headache either currently or in the past. This usually points to the diagnosis of migraine, particularly if the headache is associated with nausea and vomiting, or vertigo. Chronic, non-progressive headache usually does not have a family history. r. Is there anything important in the social and emotional history and school performance, and the pressure to obtain high grades from peers, teachers, and parents? This is a very important aspect of history and must be inquired of, in every case of headache in a child. General and neurological examination The physical and neurological examination of such children should be done while keeping in mind such diseases that come in the immediate differential diagnosis during history taking. The vital signs including blood pressure, temperature, and organomegaly should be recorded. The gait should be examined to see if there is any evidence of subtle hemiparesis, ataxia, or hysterical gait. They should be examined for Romberg s sign and for proximal and distal weakness. The head should be examined for size, and if it is large, it might suggest macrocephaly, hydrocephalus, or neurofibromatosis. Head should also be auscultated, looking for a possible machinery-like murmur that might indicate intracranial vascular anomaly such as an arteriovenous malformation or a caroticocavernous fistula. Cranium should be examined for areas of tenderness or skeletal defect. Fundoscopic examination is very important, and the fundus should be looked at searching for papilloedema, other optic head changes and haemorrhages. Ocular movements and examination of pupil should be done next. A sixth nerve weakness is a Journal, Indian Academy of Clinical Medicine Vol. 6, No. 1 January-March,

6 common non-specific finding in raised intracranial pressure. A combination of cranial nerve signs, with ataxia and dysarthria suggests a posterior fossa or brainstem lesion. At the end of history taking and physical examination, the suspected specific headache type should be categorised into one of the known patterns of headache which include: (a) an acute, first time headache pattern; (b) a recurrent, acute headache pattern; (c) chronic headache with progressive decline in neurological status; (d) a chronic, non-progressive headache; and (e) a mixed headache. If it falls into one of these well-known headache patterns, one should try to find what may be the probable aetiology. Diagnostic tests The majority of patients with migraine or with chronic non-progressive headache with absence of other symptoms and signs will not need diagnostic testing. Laboratory tests are however required in some and should be done in a rational manner with the aim of establishing the final diagnosis. Routine tests are rarely helpful. But if the history, or physical, or neurological examination suggests an organic cause, one needs to order certain diagnostic tests of which there are two main classes: (a) neuroimaging; and (b) laboratory investigations. Neuroimaging : CT Scan, MRI, and MR angiography have revolutionised the diagnosis of space occupying lesions of the intracranial space, and have been extremely valuable in the diagnosis of a wide variety of other diseases including congenital malformations, intracranial infections and their sequelae, head trauma and its sequelae, degenerative and vascular diseases. In many acute situations, it can be a life saving procedure. Of all the neuroimaging methods, it is the MRI which is most valuable in a headache patient. Although it costs more, takes a longer time, and may require sedation, it demonstrates lesions much earlier and much more clearly and accurately, particularly the sellar and parasellar lesions, craniocervical junction lesions, white matter diseases and congenital anomalies, than the CT scanning does. In such patients, where the history is suggestive of a vascular problem, MR angiography may be necessary at the same time as the MRI. No contrast is needed in MR angiography. It is a non-invasive procedure and if it is done on a high resolution machine, the images are very clear and informative. Where one suspects a venous occlusion or primary intracranial hypertension, MR venography with MRI can be diagnostic. Laboratory tests: Some of these patients will need specialised laboratory tests but the choice of the test will depend on the differential diagnosis the physician has made on the basis of the history, physical, and neurological examination. Routine blood rests in patients without any sign of progressive disease or normal examination are not helpful. If however, the patient is acutely ill, several of these tests are valuable and the selection of the specific tests will depend upon the illness one suspects. EEG which is commonly ordered by physicians, is of practically no value in the diagnosis of an average case of headache which has no evidence of an organic disease. On the other hand, physicians may also be misled by nonspecific abnormalities reported in many of these records in children who are otherwise normal. And if a focal generalised slowing is discovered, neuroimaging will be necessary to establish the diagnosis, in any case. Lumbar puncture is useful in determining the presence of an infective process affecting the brain and meninges. However, it is contraindicated in a case of headache caused by intracranial space occupying lesion, because it may cause brain herniation; and in such cases, if it is indicated, it must be done very cautiously, only after neuroimaging. If an acute infective process such as an acute bacterial meningitis or a chronic meningitis such as tuberculous meningitis is suspected, and if there is no papilloedema,it may sometime become necessary to perform lumbar puncture without waiting for the CT or MRI. In a case where one suspects primary intracranial hypertension, it may be very important to measure CSF pressure for diagnosis, and CSF drainage through lumbar puncture may be needed as a form of treatment. Preventive treatment of childhood migraine After the diagnosis of migraine is established, or when it is strongly suspected, one may initiate the treatment. After 28 Journal, Indian Academy of Clinical Medicine Vol. 6, No. 1 January-March, 2005

7 starting treatment, patients need to report for follow-up as well, every 4 to 6 weeks at least initially. All patients are first asked to avoid any provoking agents or situations as best as possible. Over-the-counter (OTC) medications need to be avoided, unless they are really necessary. Analgesics and antiemetic compounds should however be used whenever necessary, to suppress an acute attack. It is important that both the child and the parent are explained everything about the nature of the illness, the correct use of medications, their dosage, potential for misuse, and side effects. At every follow-up visit, the course of the headache should be reviewed, and if there is any suspicion of a change in the pattern such as the headache becoming more severe, more frequent, or there are new neurologic signs neuroimaging should be ordered and other tests considered. If the child has been responsive to treatment and general measures, he or she should then be followedup routinely every few months. Use of drugs as prophylactic agents in childhood and adolescent migraine Several pharmacologic agents have been studied for prevention of migraine in children and the list includes propranolol 7, timolol 8, cyproheptadine 9, naproxen 10, amitriptyline 11, clonidine 12, pizotifen 13, nimodipine 14, trazodone hydrochloride 15, dihydroergotamine 16, flunarizine 17. But many of the studies on these drugs are small, and involve only a few children, and therefore do not reach the required statistical significance, to prove their efficacy beyond doubt. None of these drugs till date has been found to have a known mechanism of action, and therefore it is unclear how they provide any relief in headache whenever they do. However, most of them are presumed to act through one of the four main mechanisms: (a) 5HT 2 antagonism; (b) modulation of plasma extravasation; (c) modulation of central aminergic control mechanism; and (d) membrane stabilising effect, through voltage sensitive channels 18. Divalproex sodium has recently been shown to be effective in migraine prophylaxis in adults, and it is supposed to exert its effect by suppressing migraine related cortical events 19. Other new drugs that have been used are, gabapentin, topiramate and baclofen. Gabapentin probably exerts its effect in migraine prevention via a pathway other than GABA neurotransmission, because although it is structurally related to gamma aminobutyric acid (GABA), it does not act at the GABA receptors, and is also not converted to GABA. Baclofen has also been reported to be effective as a migraine preventing agent, but the mechanism remains unclear 20. There is a new experimental drug called Dotarizin, which is a 5HT2 receptor agonist and has recently been reported to be a good prophylactic drug 21. This is the first report of a real designer drug for preventive treatment of migraine. All this means that there are a host of agents available from which the physician may choose a drug that he likes, although the appropriate dosage for several of these are still not known. There is always a scope of changing over from one drug to another, if one is found ineffective or toxic. The ones that have been used most frequently include beta blockers (mainly propranolol), antidepressants (tricyclic antidepressants and serotonin selective reuptake inhibitors) antihistaminics (mainy cyproheptadine), calcium channel blockers (mainly flunarizine), anticonvulsants (mainly divalproex sodium) non-steroidal anti-inflammatory agents (mainly naproxen sodium). 1. Beta blocker: Propranolol Although the evidence that propranolol is effective in migraine prophylaxis is weak, it remains the mainstay in the therapy of migraine headache in children. Its dosing has also not been systematically established. A commonly accepted starting dose of propranolol is 1 mg/kg/day divided into twice daily doses. The dose can be titrated by slowly increasing it over succeeding two to four weeks to a maximum of 3 to 4 mg/kg/day if tolerated. Many adolescent females may notice a drop in their blood pressure and complain of feeling weak and dizzy. It can also reduce stamina, and should therefore be used cautiously in athletes. It is contraindicated in bronchial constricting diseases, diabetes, and cardiac arrhythmias, and can also lead to depression. Some children experience nightmares and vivid dreams. Patients on propranolol Journal, Indian Academy of Clinical Medicine Vol. 6, No. 1 January-March,

8 should be evaluated every 2 to 3 months to see if it has been effective and also well tolerated. It is also important to remember that beta blockers may take several weeks to have their full effect. Other beta blockers have also been used for several years, but their efficacy has not been established. 2. Antidepressants: The ones that have been tried most are amitriptyline,nontriptyline and SSRIs. a. Amitriptyline: The tricyclic antidepressant amitriptyline has been reported to reduce headache frequency in children, but its efficacy has not been studied in a placebo controlled double blind trial. Moderate-to-excellent improvement with amitriptyline has been reported in one study 22. The appropriate dose of this drug has also not been determined, but clinical experience suggests that a reasonable starting dose of amitriptyline for a 5 to 10 years old child could be 5 to 10 mg per day given at bed time, and for an adolescent a 10 mg daily dose is a reasonable starting dose. Children may notice drowsiness in the early phases of treatment, but it tends to disappear in 2 to 3 weeks. At the end of a six week period, the drug dose can be titrated to reach higher efficacy without side effects. Amitriptyline is a potentially cardiotoxic drug and an ECG examination may be necessary to monitor the doses periodically. b. Nortriptyline: This drug has also been widely used as an alternative to amitriptyline in the hope that there are fewer side effects. The usual starting dose in a child in 10 mg per day administered at bed time. Side effects are similar to those of amitriptyline. c. Serotonin selective re-uptake inhibitors (SSRIs): These agents have been studied in adults, but not in children. Since there are no data to support their use in migraine prevention in children, they should be used with caution. 3. Cyproheptadine: This is an antihistaminic with antiserotinergic properties and was one of the earliest medications reported to be efficacious in migraine prophylaxis 23. Cyproheptadine can be used as a single daily dose administered at bed time. The starting dose is usually 2 to 4 mg per day. The vast majority of patients respond to a dose between 4 and 12 mg per day. But it can cause sedation and weight gain. 4. Calcium channel blockers: Calcium channel blockers have been used quite extensively in the adult population. Flunarizine, a calcium channel blocker has been used quite extensively in India, over past 12 years. It has been shown to be effective as a preventive medication in some studies in children 24,25. The actual change in headache frequency is small, but statistically significant. Side effects in adults include depression, hypokinesia, nausea, weight gain. But they are of limited usefulness in prevention of childhood migraine and have not been used much. 5. Anticonvulsants Many anticonvulsants have been used for migraine prevention including phenobarbital, carbamazepine, phenytoin, divalproex sodium, gabapentin, and topiramate, but it is the valproate which has received maximum attention recently. Divalproex sodium has been found to be effective in reducing headache frequency in adults 26,27 and it may be a good migraine preventing drug agent in children as well. Clinical experience suggests that a starting dose of 10 mg/ kg/day divided into twice daily doses may be a safe starting dose. This can be increased in the second week of treatment to 15 to 20 mg/kg/day, divided either twice or thrice daily. A serum drug level between 50 and 80 microgram/ml is considered to be adequate to control migraine headache. It has however the disadvantage of causing sedation, increase in appetite, weight gain, and temporary hair loss. Extended release preparations of divalproex sodium are now available in India which can be given as a single dose at bed time as a 250 mg tablet or 500 mg tablet. 30 Journal, Indian Academy of Clinical Medicine Vol. 6, No. 1 January-March, 2005

9 6. Naproxen sodium The non-steroidal anti-inflammatory agent, naproxen sodium is well known as an effective drug in the treatment of acute migraine headache but has also been now reported to be effective as a migraine preventive drug. Although the study has been small, there has been significant reduction in the frequency and severity of headache 10. It is given in a starting dose of 10 mg/kg/day twice daily. Long-term use of this drug may not be advisable because of its effect on the gut and renal function, but in some patients this may be a reasonable short-term alternative. There are no well controlled clinical trials to support the efficacy of any pharmacologic agent in the preventive treatment of migraine headache in children, but data are beginning to come out on the use of amitriptyline and divalproex sodium, which indicate that these agents may give some true effect. A very important question how long to treat an individual with preventive medication? Currently, it remains unanswered, and there is no consensus available on this issue. Treatment period ranging from a short period of three months to as long as eighteen months has been suggested; but six months is the mean. Personal experience however, suggests that a treatment for nine to fifteen months may result in a significant reduction in frequency and also maintains a persistent effect after withdrawal of medication. In summary, a thorough evaluation of every child with headache is essential before treatment is started. Prevention of migraine, which is perhaps the most frequent cause of headache in children, includes not only the use of pharmacological agents, but also a complete assessment of the patient s life-style, possible stressors as well as an accurate assessment of the abortive therapy available today in the medicine market. Although preventive therapy is not as effective as one would wish, further research in the underlying mechanisms of headache will, one day hopefully not in distant future develop designer drugs which are both safe and really effective. References 1. Linet MS, Stewart WF, Celentano DD et al. An epidermiologic study of headache among adolescents and young adults. JAMA 1989; 261: Abu-Arifeh I, Russel G. Prevalence of headache and migraine in school children. BMJ 1994; 309: Banaaa DS, Leviton A, Swidler C et al. A computer based headache interview: acceptance by patients and physicians. Headache 1980; 20 (2): Schechter NL. Recurrent pains in children: An overview and approach. Pediatr Clin North Am 1984; 31: Richardson GM, McGrath PJ, Cunningham ST. Validity of headache diary for children. Headache 1983; 23: Newman LC, Lipton RB, Solomon S. Headache history and neurological examination, In Headache, Diagnosis and Treatment: Tollison and Kunkel (Eds): 1993; pp Ludvigsson J. Propranolol used in prophylaxis of migraine in children. Acta Nelurol Scandinavic 1974; 50: Noronha MO. Double blind randomised cross over trial of timolol in migraine prophylaxis in children. Cephalalgia 1985; 5 (Suppl. 3): Elser JM, Woody RC. Migraine headache in the infant and young child. Headache 1990; 30: Lewin DW, Middle brook M, Mehallick M et al. Naproxen for migraine prophylaxis. Ann Neurol 1994; 36: 542 (Abstract). 11. Hersshey AD, Powers SW, Brenntti AL et al. Standard dosing of amitryptiline is highly effective in a pediatric headache center population. Headache 1999; 39: (Abstract). 12. Sillappa M. Clonidine prophylaxis of childhood migraine and other vascular headache. Headache 1977; 17: Salmon M. Pizotifen (BC 105 Sanomigran) in prophylaxis of childhood migraine. Headache 1995; 35: Battistella PA, Ruffilli R, Moro R et al. A placebo controlled crossover trial of nimodipine in pediatric migraine. Headache 1990; 30: Battisella PA, Rufilli R, Cometli R et al. A placebo controlled cross over trial using trazodone in pediatric migraine. Headache 1993; 33: Pothmann R, Winter K, Winter K. Migraine prophylaxis with dihydroergotamine-a double blind placebo controlled study. Headache 1998; 9: Ssorge F, De Sssssismone R, Marano E et al. Flunarizine in prophylaxis of childhood migraine. Cephalalgia 1988; 8: Goadsby PS. How do currently used prophylactic agents work in migraine? Cephalalgia 1997; 17: Cutter FM, Limmroth V. Moskowitz VA. Possible mechanisms of valproate in migraine pophylaxis. Cephalalgia 1997; 17: Hermig-Hanit R. Baclofen for prevention of migraine. Cephalalgia 1999; 19: Diamond S, Ryan RE, Klappel JA et al. Dotarizine in the prophylaxis of migraine headache. Headache 1999; 39: 350. Journal, Indian Academy of Clinical Medicine Vol. 6, No. 1 January-March,

10 22. Lavanstein B. A comparative study of cyproheptadine, amtriptiline and propranolol in the treatment of preadolescent migraine. Cephalalgia 1991; 11 (Suppl. 11): Billie B, Ludvigsson J, Sanner G. Prophylaxis of migraine in children. Headache 1977; 17: Sorge F, Marano E. Flunarizine v placebo in childhood migraine. A double blind study. Cephalalgia 1985; 5 (Suppl. 2): Guidetti V, Mascato D, Ottauiano S et al. Flunarizine and migraine in childhood. Cephalalgia 1987; 7: Klapper J. Divazlproex sodium in migraine prophylaxis. A dose-controlled study. Cephalalgia 1997; 17: Cariso JM, Ferri R, Exil G et al. The efficacy of divalproex sodium in the prophylactic treatment of migraine. Ann Neurol 1998; 454: 567. Diamicron MR 32 Journal, Indian Academy of Clinical Medicine Vol. 6, No. 1 January-March, 2005