Case 2: Chronic daily headache in a teenager

A 16-year-old boy presented to a paediatric neurology clinic with a six-month history of daily headaches. The headache developed fairly suddenly with no antecedent events. There was no aura preceding the headache pain. The headache was consistently left-sided with a constant feeling of pressure in the left temple, radiating into the left eye and neck, and rarely toward the right eye. The headache was described at times as stabbing and aching. Intermittently, above the continuous pain, he would have more severe exacerbations during which his left eye would become watery and light sensitive, associated with clear rhinorrhea. The exacerbations could last 30 min to 3 h, and could be triggered by positional change and exercise. Exacerbations occurred at any time of the day and even in the middle of the night. The patient used ibuprofen and acetaminophen with some relief, and gradually developed a pattern of frequent daily analgesic use. There had been no clear antecedent event before the onset of headache. Medical history was significant for recurrent otitis media with tympanostomy tubes in early childhood, two mild concussions and multiple fractures from sports injuries. He had a comorbid diagnosis of obsessive-compulsive disorder for which he was on fluvoxamine. Despite his mental health difficulties, no recent psychosocial stressors were described. He had environmental allergies. A positive family history for migraine in the mother and maternal grandmother, and a younger sister with transient neonatal seizures was noted. His vital signs and general physical examination were normal. He gave the impression of being in mild chronic pain. Mental status examination was normal. Cranial nerve examination showed no abnormalities including fundoscopy. Motor strength, tone and reflexes were normal. Sensory examination was normal and no balance or coordination changes were seen. A computed tomography (CT) of the head was normal. An initial diagnosis of chronic daily headaches from analgesic overuse was made, and he was taken off all analgesic medications with no resolution of symptoms after four weeks. On establishing that he did not have medication-overuse headache, he was started on a medication that alleviated his symptoms and clarified the diagnosis. The boy was started on a trial of indomethacin at a dose of 25 mg three times daily, with complete resolution of his headaches within two days. He had no further headaches and remained on indomethacin treatment for four months, and then gradually tapered off with no further recurrences. This dramatic and complete response to indomethacin solidified the diagnosis of hemicrania continua. Headaches are a common problem in children and adolescents. The incidence of headaches in children aged seven years and older is approximately 33%. However, they occur on a frequent basis in approximately 2.5% of the paediatric population. The incidence of headaches in those aged 15 years and older is slightly higher at approximately 50%, with frequent occurrences in approximately 15% of that population. Headaches are known to be more common in boys before puberty, with higher female preponderance postpuberty. General population studies suggest that headaches account for 10% of all school absences. Chronic daily headache presents a particular challenge to the health care provider because several primary and secondary etiologies can have a similar manifestation. Table 1 lists the more common considerations for children presenting with frequent or daily headaches (1). Causes of chronic daily headaches in children Causes of chronic daily headaches in children Indomethacin-responsive headaches (IRHs) are uncommon in paediatrics, but of importance given their rapid and complete response to indomethacin. In fact, the response to indomethacin is effectively diagnostic as well as therapeutic, and may eliminate the need for other more expensive or invasive tests if considered early. The true IRHs seen in the paediatric population are hemicrania continua and paroxysmal hemicrania. With these headaches, a complete response to indomethacin is part of the diagnostic criteria. Exertional headaches and primary stabbing headaches are also highly responsive to indomethacin but do not require a response for diagnosis. Diagnostic criteria for these headache syndromes are itemized in Table 2. Atypical patterns of hemicrania continua and paroxysmal hemicrania, such as bilateral head pain, lack of autonomic features, and temporomandibular and otic pain, do occur in paediatric patients. Consideration should be given for a trial of indomethacin in the setting of persistent daily headache or paroxysmal headaches of short duration that do not fit the typical diagnostic criteria for migraine and/or tension-type headache. However, this needs to be within the context of a normal neurological examination and all secondary causes of headache should be ruled out. Indomethacin-responsive headaches in children Headache for more than three months fulfilling criteria B to D All of the following characteristics: unilateral (one-sided pain without side shift), daily and continuous, without pain-free periods; and moderate intensity, but with exacerbations of severe pain At least one of the following autonomic features occurs during exacerbations and ipsilateral to the side of pain: conjunctival injection and/or lacrimation; nasal congestion and/or rhinorrhea; ptosis; and/or miosis Complete response to therapeutic doses of indomethacin At least 20 attacks Attacks of severe unilateral orbital, supraorbital and/or temporal pain always on the same side lasting 2 min to 30 min Attack frequency more than five per day for more than half of the time (periods with lower frequency may occur) Pain associated with at least one of the following signs/symptoms on the symptomatic side: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, ptosis and/or miosis and eyelid edema Absolute effectiveness of indomethacin in therapeutic doses Headache specifically brought on by and occurring during or after physical exercise Pulsating in nature Lasts from 5 min to 48 h Head pain occurring as a single stab or a series of stabs Exclusively or predominantly felt in the distribution of the first division of the trigeminal nerve Stabs last for up to a few seconds and recur with irregular frequency ranging from one to many per day No accompanying symptoms Not attributed to another disorder Headache for more than three months fulfilling criteria B to D All of the following characteristics: unilateral (one-sided pain without side shift), daily and continuous, without pain-free periods; and moderate intensity, but with exacerbations of severe pain At least one of the following autonomic features occurs during exacerbations and ipsilateral to the side of pain: conjunctival injection and/or lacrimation; nasal congestion and/or rhinorrhea; ptosis; and/or miosis Complete response to therapeutic doses of indomethacin At least 20 attacks Attacks of severe unilateral orbital, supraorbital and/or temporal pain always on the same side lasting 2 min to 30 min Attack frequency more than five per day for more than half of the time (periods with lower frequency may occur) Pain associated with at least one of the following signs/symptoms on the symptomatic side: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, ptosis and/or miosis and eyelid edema Absolute effectiveness of indomethacin in therapeutic doses Headache specifically brought on by and occurring during or after physical exercise Pulsating in nature Lasts from 5 min to 48 h Head pain occurring as a single stab or a series of stabs Exclusively or predominantly felt in the distribution of the first division of the trigeminal nerve Stabs last for up to a few seconds and recur with irregular frequency ranging from one to many per day No accompanying symptoms Not attributed to another disorder The diagnostic criteria include no other secondary explanation for the headaches. Data adapted from reference 3 Indomethacin-responsive headaches in children Headache for more than three months fulfilling criteria B to D All of the following characteristics: unilateral (one-sided pain without side shift), daily and continuous, without pain-free periods; and moderate intensity, but with exacerbations of severe pain At least one of the following autonomic features occurs during exacerbations and ipsilateral to the side of pain: conjunctival injection and/or lacrimation; nasal congestion and/or rhinorrhea; ptosis; and/or miosis Complete response to therapeutic doses of indomethacin At least 20 attacks Attacks of severe unilateral orbital, supraorbital and/or temporal pain always on the same side lasting 2 min to 30 min Attack frequency more than five per day for more than half of the time (periods with lower frequency may occur) Pain associated with at least one of the following signs/symptoms on the symptomatic side: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, ptosis and/or miosis and eyelid edema Absolute effectiveness of indomethacin in therapeutic doses Headache specifically brought on by and occurring during or after physical exercise Pulsating in nature Lasts from 5 min to 48 h Head pain occurring as a single stab or a series of stabs Exclusively or predominantly felt in the distribution of the first division of the trigeminal nerve Stabs last for up to a few seconds and recur with irregular frequency ranging from one to many per day No accompanying symptoms Not attributed to another disorder Headache for more than three months fulfilling criteria B to D All of the following characteristics: unilateral (one-sided pain without side shift), daily and continuous, without pain-free periods; and moderate intensity, but with exacerbations of severe pain At least one of the following autonomic features occurs during exacerbations and ipsilateral to the side of pain: conjunctival injection and/or lacrimation; nasal congestion and/or rhinorrhea; ptosis; and/or miosis Complete response to therapeutic doses of indomethacin At least 20 attacks Attacks of severe unilateral orbital, supraorbital and/or temporal pain always on the same side lasting 2 min to 30 min Attack frequency more than five per day for more than half of the time (periods with lower frequency may occur) Pain associated with at least one of the following signs/symptoms on the symptomatic side: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, ptosis and/or miosis and eyelid edema Absolute effectiveness of indomethacin in therapeutic doses Headache specifically brought on by and occurring during or after physical exercise Pulsating in nature Lasts from 5 min to 48 h Head pain occurring as a single stab or a series of stabs Exclusively or predominantly felt in the distribution of the first division of the trigeminal nerve Stabs last for up to a few seconds and recur with irregular frequency ranging from one to many per day No accompanying symptoms Not attributed to another disorder The diagnostic criteria include no other secondary explanation for the headaches. Data adapted from reference 3 In hemicrania continua, most cases occur in female patients and the age of onset ranges from 10 to 58 years. Patients treated with indomethacin report complete relief of symptoms between 24 h to 72 h after starting treatment. Doses can vary from 50 mg/day to 300 mg/day, with an average of 75 mg/day in divided doses needed for most paediatric patients. A starting dose of 25 mg three times daily is recommended. The dosage should be increased to 50 mg three times per day if the patient has not responded within 48 h. A dose of 100 mg three times daily should be achieved for a week before eliminating the possibility of an IRH. Typically, patients are maintained on indomethacin for at least three months before weaning, but may need a longer term of therapy to avoid headaches (2). Indomethacin was discovered in 1963 for its potent anti-inflammatory, analgesic and antipyretic properties via cyclooxygenase inhibition and prevention of prostaglandin synthesis. The main mechanism in controlling headaches stems from its function as a potent cerebral vasoconstrictor, which is a special property of indomethacin differing from other nonsteroidal anti-inflammatory drugs (NSAIDS). It is known to reduce cerebral blood flow by 18% to 50%, while leaving cerebral metabolism unchanged. Indomethacin also acts as a free radical scavenger and interferes with calcium transport. There is good oral absorption of indomethacin, with a 2 h delay in plasma concentration when consumed with meals. It is 90% plasma bound with 60% renal excretion in 48 h. It is available both orally and rectally. It is important to recognize the high incidence of side effects with chronic use of indomethacin. Gastrointestinal side effects including dyspepsia, nausea, vomiting, vertigo and gastric bleeding are commonly reported. To prevent gastric adverse effects, antacids, an H2 antagonist or proton pump inhibitor may be co-administered when indomethacin is being used for longer periods. An indomethacin suppository is another option for gastric intolerance or when a higher dose (eg, 300 mg/day) is needed. Interestingly, frontal headache has been reported as a side effect as well. Other rare side effects include hypersensitivity reactions, suicidal behaviour and severe depression, psychosis, and renal impairment. Patients should be cautioned against using other NSAIDs while on indomethacin to avoid potentiating any gastrointestinal side effects. Patients should also be cautioned against using other medications such as anticoagulants, diuretics, methotrexate, cyclosporine and antihypertensive agents. The main contraindication remains in patients in whom acute asthmatic attacks, urticaria or rhinitis are precipitated by administration of this drug or known to have a similar reaction to other NSAIDS. IRH syndromes are uncommon in the paediatric population and so may be easily overlooked in clinical practice due to lack of knowledge. IRH syndromes have a rapid and dramatic response to indomethacin soon after administration. A trial of indomethacin for headaches not responding to conventional medication may be warranted provided secondary causes of intractable headache have been ruled out and the neurological examination is normal. In these cases, a short course of indomethacin is beneficial as a diagnostic procedure. At least three months of treatment are recommended before trying to wean the medication.

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