Pediatric Annals

CME Article 

Secondary Causes of Headaches in Children: When It isn’t a Migraine

Heidi K. Blume, MD, MPH; Christina L. Szperka, MD

Abstract

Headaches are common in children and adolescents. Seventeen percent of children in the United States report frequent or severe headaches,1 and headaches are a common complaint in the emergency department and at office visits. Fortunately, most childhood headaches are due to a primary headache disorder or benign process, such as a viral infection. However, medical providers must also consider other secondary causes of headaches in children. Delayed or missed diagnosis of an underlying disorder causing headache can lead to significant morbidity and prolonged suffering. In this review, we discuss some of the most common and most ominous secondary causes of pediatric headache.

Abstract

Headaches are common in children and adolescents. Seventeen percent of children in the United States report frequent or severe headaches,1 and headaches are a common complaint in the emergency department and at office visits. Fortunately, most childhood headaches are due to a primary headache disorder or benign process, such as a viral infection. However, medical providers must also consider other secondary causes of headaches in children. Delayed or missed diagnosis of an underlying disorder causing headache can lead to significant morbidity and prolonged suffering. In this review, we discuss some of the most common and most ominous secondary causes of pediatric headache.

Heidi Blume, MD, MPH, is Assistant Professor, Division of Pediatric Neurology, Seattle Children’s Hospital. Christina L Szperka, MD, is Resident in Neurology, Hospital of the University of Pennsylvania and Children’s Hospital of Philadelphia.

Dr. Blume and Dr. Szperka have disclosed no relevant financial relationships.

Address correspondence to: Heidi Blume, MD, MPH; fax: 206-987-2649; e-mail heidi.blume@seattlechildrens.org.

Headaches are common in children and adolescents. Seventeen percent of children in the United States report frequent or severe headaches,1 and headaches are a common complaint in the emergency department and at office visits. Fortunately, most childhood headaches are due to a primary headache disorder or benign process, such as a viral infection. However, medical providers must also consider other secondary causes of headaches in children. Delayed or missed diagnosis of an underlying disorder causing headache can lead to significant morbidity and prolonged suffering. In this review, we discuss some of the most common and most ominous secondary causes of pediatric headache.

Abnormal Intracranial Pressure

Elevated intracranial pressure (ICP) is an important cause of pediatric headaches and has various causes. Noncommunicating hydrocephalus may result from blockage of CSF flow by congenital aqueductal stenosis or a space-occupying lesion. Communicating hydrocephalus can result from hemorrhage, infection, or other disorder that impairs absorption of CSF. Increasing the volume of tissue or fluids in the cranial vault (eg, intracranial tumors, mass lesions, edema, inflammation, or hemorrhage) will lead to a dramatic increase in ICP once the intracranial volume passes a certain threshold (see Figure).

Relationship of ICP to Intracranial Volume

Figure. Relationship of ICP to Intracranial Volume

Headaches are the most common presenting symptom of elevated ICP. Typically, these headaches are progressive, may cause night wakening, and are worse with Valsalva’s maneuver or exertion. Children with elevated ICP often experience persistent vomiting, neurological deficits, lethargy, or personality change. Other signs of elevated ICP include papilledema and palsies of 3rd, 4th, or 6th cranial nerves, resulting in eye movement or pupillary abnormalities. Cushing’s triad (hypertension, bradycardia, and respiratory depression) is a late sign of impending transtentorial herniation.

Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension (IIH) is elevated ICP without evidence of responsible infection, vascular abnormality, space occupying lesion, or hydrocephalus.2 Daily headache is the most common symptom related to IIH, and it may be associated with nausea and vomiting and other migrainous features, but the headache is often poorly characterized. Classic symptoms of IIH include transient obscuring of vision, tinnitus, and diplopia caused by cranial nerve dysfunction, particularly 6th nerve palsy. Minor symptoms of IIH include paresthesias, neck stiffness, arthralgias, ataxia, and radicular pain. In young children, the most common complaints are headache, stiff neck, strabismus, irritability, apathy, somnolence, dizziness, and ataxia.3

Children are more likely to have an underlying condition associated with elevated ICP than adults (see Table 1, page 433), so a thorough evaluation, including history, exam, magnetic resonance imaging (MRI), magnetic resonance veonography (MRV), ophthalmological exam, and lumbar puncture with accurate assessment of opening pressure and CSF analysis, is essential when IIH is suspected in a child.4 IIH is more common in adolescents than young children, and the patterns of IIH in adolescence are similar to adult IIH patterns. More girls than boys are affected, and obesity is associated with IIH. However, in younger children, the sexes are equally affected, and obesity is not strongly associated with IIH.4

Conditions Associated with IIH3,4

Table 1. Conditions Associated with IIH3,4

Treatment of IIH first involves management or removal of any associated causes of intracranial hypertension. Medical management of IIH includes use of acetazolemide until symptoms resolve. If children are unable to tolerate acetazolemide, other options include furosemide or topiramate, or possibly zonisamide.4 Surgical management is sometimes required for patients who do not respond to, or cannot tolerate, medical therapy. The two major surgical options are optic nerve sheath fenestration and CSF shunting. These procedures can be associated with a variety of complications, so consultation with an experienced ophthalmologist and neurosurgeon is essential.

Intracranial Hypotension

Low intracranial pressure can also be associated with headaches. These headaches are usually worse when the patient is upright and improve when the patient is recumbent. The headache characteristics are quite variable, may be acute or chronic, and may have migrainous features. Low pressure headaches are typically associated with some form of CSF leak, most commonly following surgery, trauma, or lumbar puncture. Patients with connective tissue disease (eg, Marfan’s syndrome) may have dural ectasias that place them at risk for spontaneous CSF leaks. Diffuse pachymeningeal enhancement is the classic finding of intracranial hypotension on MRI. Management is variable and may include rest, caffeine, epidural blood patch, aggressive hydration, and surgical repair, but there are few studies in this area and treatment requires an individualized approach.

Infection

Acute Viral Illness

Acute viral illness with fever is the most common cause of pediatric headache evaluated in the emergency department (see Table 2, page 434).5,6 Typically, these children have acute onset of headache, are not seriously disabled by the headache, and the headache resolves as the other viral symptoms dissipate.

Secondary Causes of Acute Headache

Table 2. Secondary Causes of Acute Headache

Sinus Disease

Although sinusitis may cause or trigger headaches in some children, most patients diagnosed with “sinus headaches” actually have some form of primary headache.7,8 It is common to find a description of “sinus disease” on computerized tomography (CT) or MRI done to investigate headache in a child without symptoms of sinusitis. Often, treatment of this “sinusitis” does not improve the child’s headaches.8 Sinus-related pain is generally pressure-like and dull periorbital pain, worse in the morning, associated with nasal congestion, lasts for days at a time, and is not associated with nausea, visual changes, phonophobia, or photophobia.7

Intracranial Infection

Meningitis and encephalitis are the cause of acute headaches in 2% to 9% of children evaluated for headache in the ER.9 Headaches due to meningitis are often associated with photophobia, nausea, vomiting, and pain with eye movements. Patients with meningitis typically exhibit other symptoms, such as fever, altered mental status, and nuchal rigidity, although fungal meningitis may be more indolent. Encephalitis is typically associated with fever and altered mental status. Given the risk of elevated ICP, head CT should be considered before lumbar puncture, and antibiotic administration should be considered urgently in critically ill patients with suspected intracranial infection.

Brain Abscess

Brain abscess is a rare cause of headache, and the classic symptoms of a brain abscess include headache, fever, and focal neurological deficit. The presentation may be acute or evolve over weeks to months.

Brain abscesses can be caused by spread of a local infection (eg, sinusitis, dental infection), hematological spread of distant infection, trauma or surgery. Immunocompromised individuals with headache should have a thorough evaluation for intracranial infections.

Systemic Infection

Many systemic infections can be associated with headache, including streptococcal pharyngitis, sepsis, Lyme disease, bartonella, rickettsial diseases, HIV, and viral infections. Headache is rarely the only symptom, so thorough history and exam are essential to identify successfully and treat the underlying disorder. At times, a viral infection, particularly with Epstein-Barr virus, can be associated with the onset of new daily persistent headaches, even in the absence of intracranial or chronic infection.10

Structural Disorders

Tumor

Many families are terrified that their child’s headache is caused by a brain tumor. Fortunately, brain tumors are relatively uncommon in children (4.5/100,000 person years). Brain tumors can cause headache via hydrocephalus, mass effect, or hemorrhage. Several risk factors are associated with an intracranial space-occupying lesion, including sleep-related headache, absence of family history of migraine, headache of less than 6 months’ duration, confusion, abnormal neurological exam, lack of visual aura symptoms, and vomiting. Children with more risk factors have a higher risk of having a surgical brain lesion.11 Other worrisome symptoms include headache associated with cough, urination or defecation, recurrent and focal headache, occipital headache, change in headache type, and progressive increase in headache frequency or severity. This topic is addressed by Lewis and Koch in this issue (see page 399). One should consider a brain tumor if the child has symptoms noted above, or if the child has a history of exposure to ionizing radiation or a syndrome (such as tuberous sclerosis or neurofibromatosis) that is associated with brain tumors.

Chiari I Malformation

Chiari I malformation is the herniation of the cerebellar tonsils more than 5 mm below the foramen magnum. Classically, the presenting symptoms of Chiari I include occipital headaches, cough headaches or syncope, sensory disturbance, weakness, ataxia, vertigo, or other cranial nerve dysfunction.12 In children, the symptoms may be more ambiguous and include headache (not always occipital), neck pain, vertigo, ataxia, and sensory changes.13 Ensuring that a headache is due to a Chiari malformation can be challenging, because more than 30% of patients with Chiari I malformation on MRI are asymptomatic, and other causes of headache are common. A study of pediatric Chiari I malformations found that none of the radiological characteristics were predictive of headaches or significant neurological symptoms.13 Definitive management of symptomatic Chiari I malformation is surgical enlargement of the posterior fossa, and most symptomatic patients improve after surgery. However, the decision to proceed with surgery should be made after careful analysis of the child’s symptoms, exam findings, and imaging by an experienced neurosurgeon.

Arachnoid Cysts

Arachnoid cysts are most often small and incidental findings on MRIs that are obtained to evaluate headaches and are found in 3% of MRIs done for HA.11 However, a large arachnoid cyst can cause increased ICP, via mass effect or blockage of CSF flow (hydrocephalus), and, thus, can cause headache. Rupture of a cyst, although very rare, can cause an acute thunderclap headache. Most arachnoid cysts do not require intervention or follow-up.11

Vascular Disorders

Intracranial Hemorrhage

Spontaneous intracranial hemorrhage (ICH) is rare in children (1.1–2.4/100,000 children).14 Although acute or “thunderclap” headache is the classical presenting symptom of ICH, most children with ICH have additional signs or symptoms by the time they present to medical care. The most common causes of ICH are congenital heart disease, arteriovenous malformations, and sepsis.14 Other causes of nontraumatic ICH include coagulation defects, purpuric disorders, brain tumors, meningitis, leukemia, cardiac arrest, autoimmune disease, and sickle cell disease. Spontaneous ICH is rare in children, but it needs to be considered in patients with acute onset of severe headache, particularly if the patient has an abnormal neurological exam or an underlying medical disorder that places them at risk for hemorrhage. This assessment should include thorough physical/neurological exam and CT scan (although MRI with gradient echo sequence may be indicated if ischemic stroke is also being considered) and other testing as appropriate for the situation.

Ischemic Stroke

Ischemic stroke is rare in children (3.7/100,000), with the highest risk in children younger than 4 years (5.9/100,000).14 Although headache may be present, it is rarely the only symptom of an ischemic stroke. In children with stroke, neurological symptoms come on abruptly and persist, do not typically progress from one side of the body to the other, and are not typically recurrent. In contrast, the symptoms of a migraine aura usually last less than 30 minutes, may involve both sides of the body, may progress from one side of the body to the other, and are often recurrent over months to years. Arterial dissection is a very rare cause of acute pediatric headache. Fifty percent of patients with arterial dissection have headaches, but all had ischemia and other symptoms.15 MRI with diffusion weighted imaging is the best technique to identify an ischemic stroke.

Sinus Venous Thrombosis (SVT)

Sinus venous thrombosis (SVT) is another uncommon cause of secondary headaches in children, diagnosed in fewer than 0.5/100,000 children older than 1 month.16,17 In addition, SVT can be difficult to diagnose, and symptom onset can be insidious, so providers need to be aware of this condition to identify patients at risk for SVT. The most common presenting symptoms of SVT in children are headache (59%), focal neurological signs (53%), seizures (48%), decreased level of consciousness (49%), and papilledema (22%). Most (97%) have some risk factor for SVT, including head/neck infection (otitis media, sinusitis), chronic systemic disease (cardiac disease, hematological disease, cancer, rheumatological disease, renal disease), or other prothrombotic state.16

SVT can also be associated with secondary infarcts and/or intracerebral hemorrhage. Therefore, although rare in typical children, SVT should be considered in patients with headache and other neurological signs and symptoms, particularly in those with underlying medical conditions that place them at risk for SVT.

Vascular Malformations

Vascular malformations can cause headache if they bleed, causing intracranial hemorrhage. Large vascular malformations can cause elevated intracranial pressure and headache via direct mass effect.

Trauma

Children with severe or progressive headache or altered mental status after head injury should be evaluated emergently. Headaches after a head injury may be caused by traumatic intracranial hemorrhage (subdural, epidural, or subarachnoid hemorrhage) or fracture but are more commonly due to post-traumatic headache without hemorrhage or fracture. A recent study developed an algorithm to identify children at low risk for clinically important brain injury after trauma and recommended that children older than 2 years with normal mental status, no signs of skull fracture, no loss of consciousness, no vomiting, nonsevere mechanism of injury, and non-severe headache did not need a CT scan after head trauma. This prediction rule had a negative predictive value of 99.95% and sensitivity of 96.8%.18 Significant injury was found in 2% of those who fulfilled criteria for scanning. Use of this algorithm would avoid scans for 20% of children who would typically be scanned following a head injury.18

Posttraumatic Headaches

Posttraumatic headaches develop within a week of head trauma or whiplash injury. These headaches may have qualities of migraine or tension headaches and are often associated with other postconcussive symptoms, including sleep disturbance, balance abnormalities, cognitive changes, and mood changes. Most posttraumatic headaches resolve within 2 weeks. Children with posttraumatic headache should not return to activities in which they are at risk for repeat head injury until they are symptom-free while active and cleared by a trained medical provider. Once symptom-free, they should return to their regular activities in a step-wise fashion, as outlined in the 2009 Zurich Consensus Statement on Concussion in Sport.19 Factors that may increase the risk of prolonged posttraumatic headaches include sustaining multiple concussions in a short period of time, female sex, pre-existing headaches, baseline learning disabilities, anxiety, or depression.

Disorders Related to the Eye and Facial Structures

Ocular Causes of Headache

Refractive error may cause headache, and correction improves the headache in most patients.20 Dry eyes, glaucoma, and optic neuritis can cause eye pain that may refer to the frontal region. Other systemic illnesses, particularly vascular and inflammatory problems, can cause visual changes, such as blurred vision and visual field changes along with headache.21

Cervicogenic Headache

Pain signals from the upper cervical cord can be referred to the head. Cervicogenic headache should be considered if there is a history of neck trauma, or if movement or palpation of the neck mimics the headache pain. The first line of treatment is physical therapy, and referral to a pediatric pain specialist if that is not effective.22

TMD/bruxism

Symptoms of temporomandibular disorders (TMD) include clicking, pain in the temporomandibular joint or masticatory muscles, jaw fatigue, and difficulty with mouth opening or lateral movement. TMD symptoms have been associated with migraine, tension-type, and chronic daily headache.23–26 Even in the absence of symptoms of TMD, malocclusion of the jaw27 and tooth problems28 can also cause headache, so careful examination of the mouth is important.

Sleep

The relationship between sleep and headaches is multifactorial:29

  1. Insufficient, excessive, poor quality, and disrupted sleep can cause headache, especially in those with a primary headache disorder, such as migraine.

  2. Sleep can treat headache attacks, especially migraine.

  3. Headaches can disrupt sleep.

  4. Sleep apnea can trigger headaches, nondescript morning headaches, and attacks of migraine or cluster headache. The mechanism may be related to hypoxia and hypercapnia, although nonrespiratory sleep disorders, such as periodic limb movements, can also provoke headaches. Treating the sleep disorder often improves the pattern of headaches.30

  5. Behavioral modifications to improve sleep hygiene have been shown to decrease headache frequency and duration.31

Consider a sleep disorder in patients whose headaches always occur at night or in the morning, whose chronic headaches are resistant to treatment, or who report snoring or other sleep problems.

Substances that Can Cause Headache

Caffeine

Caffeine can cause an immediate headache but more often provokes headaches in withdrawal. Slow elimination of daily caffeine in children with chronic daily headache has been shown to improve headache frequency.32

Alcohol

Alcohol can cause an immediate headache or a delayed “hangover headache” as the blood alcohol level declines.

Cocaine

Headache is a relatively common complaint associated with recreational cocaine use and can have features of migraine or cluster headache. It can also be a sign of serious pathology, such as stroke, hemorrhage, or abscess in cocaine users.

Pain can start immediately upon ingestion, an hour later as blood level begins to decline, during a multiple day binge, or after a few days of abstinence.33,34

Carbon Monoxide

Early carbon monoxide poisoning causes nonspecific symptoms of malaise, weakness, and headache. Studies of patients presenting to urban emergency departments during winter months with headache have found a 4% to 7% rate of occult carbon monoxide poisoning.35,36

Classically, the pain has been described as frontal tightness when carboxyhemoglobin levels are 10% to 20%, and throbbing pain with COHb between 20% and 30%, but patients’ descriptions are more variable. There are no characteristics to the headache that specifically point to this diagnosis.37

Lead

Acute and chronic lead toxicity can cause headache.38 Additional signs of lead encephalopathy (level >80 μg/dL) include impaired consciousness, seizures, papilledema, irritability, hallucinations, vomiting, ataxia, tremors, and kidney difficulties. Chronic exposure also leads to cognitive deficits, poor attention, hyperactivity, and impaired hearing.38

Medication

Headache is a relatively common adverse reaction to medications and it can be a result of the primary mechanism of action, an idiosyncratic response, or due to withdrawal. Commonly encountered examples include aseptic meningitis from nonsteroidal anti-inflammatory medications (NSAIDs) and antimicrobials and increased intracranial pressure from steroid withdrawal. Many cardiovascular medications cause headache from vasodilatation (see Table 3, page 436).39,40 Overuse of medications to treat headaches, especially analgesics, caffeine, opioids, ergotamines, and triptans, is associated with their transformation from episodic to chronic and frequent headaches.41 See the article on chronic daily headache in this issue (page 424) for more information.

Medications that Cause Headache

Table 3. Medications that Cause Headache

Systemic Disease

Metabolic Derangements and Endocrine Disorders

Fasting/eating Disorder

Fasting is a relatively common cause of headaches in children. The mechanism is unclear but may be related to caffeine withdrawal and less commonly to hypoglycemia.42 Asking a child or family to keep a headache diary is often helpful in determining an association between fasting and headache. Unmasking an eating disorder as a trigger for headaches can be challenging and requires a high index of suspicion for underlying eating disorder, a thorough physical exam and interview with the teen and parent looking for signs or symptoms of an eating disorder.

Hypoxia

High-altitude headache comes on within hours of rapid ascent into the mountains and is usually bilateral, mild, and exacerbated by activity. It is hypothesized to result from hypoxia-induced cerebral vasodilatation and can be seen in isolation or with more severe symptoms of mountain sickness. The headache usually improves with supplemental oxygen, rehydration, passage of time, descent to lower altitude, and/or analgesics.43

Hypercapnia

Hypercapnia and hypoxia occur together in sleep apnea and hypopnea from neuromuscular disease. These conditions are associated with headache, although the exact mechanism is unknown.

Thyroid

Low levels of thyroid hormone may be pronociceptive and typically cause a bilateral, nonpulsatile, continuous headache.44 Hypothyroidism has been associated with New Daily Persistent Headache and should also be considered for any refractory headache, especially when accompanied by symptoms of fatigue, depression, dry skin, slow speech, cold intolerance, weight gain, hair changes, constipation, decreased concentration, or irregular menses.45 Although thyroid replacement hormone usually improves these headaches, it can also cause headaches via idiopathic intracranial hypertension.46 Hyperthyroidism and Hashimoto’s encephalopathy are rarer causes of headache.

Parathyroid

Headache can be a presenting symptom of hyperparathyroidism but would be accompanied by other symptoms, such as fatigue, lethargy, nausea, vomiting, abdominal pain, polydipsia, and nephrolithiasis.47

Allergy

Patients with asthma and hay fever report an increased prevalence of headache, although it is unclear whether this is a causal relationship.48 Look for allergic shiners, cobblestoning, and postnasal drip on exam.

Epilepsy

Periictal headaches are common in children with partial or generalized tonicclonic seizures.49 Typically, the association between the headache and seizure will be obvious. However, some seizure disorders are characterized by episodes of altered mental status, and/or visual disturbances (typically colored and rounded objects rather than the jagged or scintillating aura seen in migraine) and followed by headache. Therefore, one should consider EEG and/or neuroimaging for children with atypical neurological symptoms at the time of their headache.

Mitochondrial Disease

Headache and migraine are frequent findings in mitochondrial disease. However, children with significant mitochondrial disease typically have other problems, such as additional neurological symptoms, hearing loss, liver disease, cardiovascular disease, ophthalmological disease, hematological abnormalities, significant gastrointestinal illness, or endocrinopathies.50 There is emerging evidence that mitochondrial dysfunction may be related to migraine in some patients.51,52 In the future, we may find that some migraineurs have mild forms of mitochondrial disease, but at this time, routine screening for mitochondrial disease in patients with isolated headache is not indicated.

Sickle Cell Disease

Children with sickle cell disease (SCD) are at risk for ischemic stroke and intracerebral hemorrhage, which can present with an acute, severe headache. They are also at risk for thrombosis and chronic anemia, which can lead to sinus venous thrombosis or idiopathic intracranial hypertension. However, they may also have migraine or tension headaches, and young children with sickle cell disease are more likely to have headaches than age-matched controls.53

Hypertension

Acute, severe headaches may be the initial sign of hypertensive crisis and severe hypertension can lead to hypertensive encephalopathy. Mild to moderate hypertension does not typically cause significant headaches.54 Measurement of blood pressure and pulse using an appropriate-sized cuff and normative data are essential.

Rheumatologic Disease

Children with rheumatologic disease, such as systemic lupus erythematosus (SLE), Behcet’s syndrome, polyarteritis nodosa, Wegener’s granulomatosis, and sarcoidosis, often have headache. The causes of headache in rheumatological disease can range from aseptic meningitis, intracranial hypertension, sinus venous thrombosis, CNS vasculitis, intracerebral hemorrhage, CNS ischemia, or headache without underlying pathology.55 Primary CNS vasculitis is a rare disorder, and is typically accompanied by other signs of CNS ischemia or inflammation. Immunosuppressive agents and NSAIDs used to treat rheumatological disorders can also cause headaches via direct “toxic” effect, aseptic meningitis, intracranial hypertension, posterior reversible encephalopathy syndrome, seizures, or intracranial infection due to immunosuppression. Thus, children with diagnosed or suspected rheumatological disease and headache should have a thorough evaluation for secondary cause of headache that may include consultation with a neurologist or rheumatologist, MRI with contrast, MRV, magnetic resonance angiography (MRA), lumbar puncture (with measurement of opening pressure and CSF analysis), and screening for inflammatory disorders as appropriate.

Gastrointestinal Disease

Studies have shown an increased rate of headache in patients with irritable bowel syndrome or Crohn’s disease,56 as well as in subjects who report reflux, constipation, diarrhea, and nausea.57 Children with biopsy-proven celiac disease report a high rate of headaches, especially migraines, and a substantial portion of these remit with the gluten-free diet.58 Studies have also found a higher prevalence of subclinical celiac disease in migraineurs and most improve on a gluten-free diet.59–62 However, the authors do not describe whether those patients had any gastrointestinal complaints to suggest the diagnosis, so it is difficult to apply this to one’s practice.

Psychiatric Disease

Mood and anxiety disorders are common in headache patients, but psychiatric disease is usually an exacerbating rather than causative factor. Headaches should be attributed to somatization disorder, psychotic disorder, major depressive disorder or anxiety, only if those symptoms are very prominent and the headaches remit with treatment of the psychiatric disorder.63

Conclusion

Although most pediatric headaches are due to benign illness or a primary headache syndrome, clinicians must be able to recognize disorders that can cause secondary headache. Failure to identify the underlying cause of a child’s headache can lead to significant morbidity and prolonged suffering. The most important factors in the evaluation of any child with headache are 1) a comprehensive history detailing headache characteristics and any disorders, symptoms or exposures that may be associated with the headache; 2) complete physical and neurological exam with attention to signs or symptoms that could be associated with a secondary cause of headache (eg, malar rash, fever, nucal rigidity, ataxia, papilledema, tooth pain, etc.); and then 3) proceeding with testing as/if indicated by the history and exam. Use of these techniques in combination with a good understanding of primary and secondary headache syndromes will enable clinicians to provide optimal care for their pediatric patients with headache.

References

  1. Lateef TM, Merikangas KR, He J, et al. Headache in a national sample of American children: prevalence and comorbidity. J Child Neurol. 2009;24(5):536–543. doi:10.1177/0883073808327831 [CrossRef]
  2. Friedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial hypertension. Neurology. 2002;59(10):1492–1495.
  3. Pseudotumor cerebri.Friedman DI. Neurol Clin. 2004;22(1):99–131, vi.
  4. Rangwala LM, Liu GT. Pediatric idiopathic intracranial hypertension. Surv Ophthalmol. 2007;52(6):597–617. doi:10.1016/j.survophthal.2007.08.018 [CrossRef]
  5. Conicella E, Raucci U, Vanacore N, Vigevano F, Reale A, Pirozzi N, Valeriani M. The child with headache in a pediatric emergency department. Headache. 2008;48(7):1005–1011. doi:10.1111/j.1526-4610.2007.01052.x [CrossRef]
  6. Lewis DW, Qureshi F. Acute headache in children and adolescents presenting to the emergency department. Headache. 2000;40(3):200–203. doi:10.1046/j.1526-4610.2000.00029.x [CrossRef]
  7. Levine HL, Setzen M, Cady RK, et al. An otolaryngology, neurology, allergy, and primary care consensus on diagnosis and treatment of sinus headache. Otolaryngol Head Neck Surg. 2006;134(3):516–523. doi:10.1016/j.otohns.2005.11.024 [CrossRef]
  8. Senbil N, Gürer YK, Uner C, Barut Y. Sinusitis in children and adolescents with chronic or recurrent headache: a case-control study. J Headache Pain. 2008;9(1):33–36. doi:10.1007/s10194-008-0007-0 [CrossRef]
  9. Schobitz E, Qureshi F, Lewis D. Pediatric headaches in the emergency department. Curr Pain Headache Rep. 2006;10(5):391–396. doi:10.1007/s11916-006-0066-3 [CrossRef]
  10. Mack KJ. What incites new daily persistent headache in children?Pediatr Neurol. 2004;31(2):122–125. doi:10.1016/j.pediatrneurol.2004.02.006 [CrossRef]
  11. Medina LS, Pinter JD, Zurakowski D, Davis RG, Kuban K, Barnes PD. Children with headache: clinical predictors of surgical space-occupying lesions and the role of neuroimaging. Radiology. 1997;202(3):819–824.
  12. Cheng JS, Nash J, Meyer GA. Chiari type I malformation revisited: diagnosis and treatment. Neurologist. 2002;8(6):357–362. doi:10.1097/00127893-200211000-00005 [CrossRef]
  13. Aitken LA, Lindan CE, Sidney S, et al. Chiari type I malformation in a pediatric population. Pediatr Neurol. 2009;40(6):449–454. doi:10.1016/j.pediatrneurol.2009.01.003 [CrossRef]
  14. Lo W, Stephens J, Fernandez S. Pediatric stroke in the United States and the impact of risk factors. J Child Neurol. 2009;24(2):194–203. doi:10.1177/0883073808322665 [CrossRef]
  15. Fullerton HJ, Johnston SC, Smith WS. Arterial dissection and stroke in children. Neurology. 2001;57(7):1155–1160.
  16. deVeber G, Andrew M, Adams C, et al. Canadian Pediatric Ischemic Stroke Study Group. Cerebral sinovenous thrombosis in children. N Engl J Med. 2001;345(6):417–423. doi:10.1056/NEJM200108093450604 [CrossRef]
  17. Wasay M, Dai AI, Ansari M, Shaikh Z, Roach ES. Cerebral venous sinus thrombosis in children: a multicenter cohort from the United States. J Child Neurol. 2008;23(1):26–31. doi:10.1177/0883073807307976 [CrossRef]
  18. Kuppermann N, Holmes JF, Dayan PS, et al. Pediatric Emergency Care Applied Research Network (PECARN). Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study. Lancet. 2009;374(9696):1160–1170. doi:10.1016/S0140-6736(09)61558-0 [CrossRef]
  19. McCrory P, Meeuwisse W, Johnston K, et al. Consensus Statement on Concussion in Sport: the 3rd International Conference on Concussion in Sport held in Zurich, November 2008. Br J Sports Med. 2009;43Suppl 1:i76–90. doi:10.1136/bjsm.2009.058248 [CrossRef]
  20. Gil-Gouveia R, Martins IP. Headaches associated with refractive errors: myth or reality?Headache. 2002;42(4):256–262. doi:10.1046/j.1526-4610.2002.02077.x [CrossRef]
  21. Friedman DI. Headache and the eye. Curr Pain Headache Rep. 2008;12(4):296–304. doi:10.1007/s11916-008-0050-1 [CrossRef]
  22. Bogduk N, Govind J. Cervicogenic headache: an assessment of the evidence on clinical diagnosis, invasive tests, and treatment. Lancet Neurol. 2009;8(10):959–968. doi:10.1016/S1474-4422(09)70209-1 [CrossRef]
  23. Gonçalves DA, Speciali JG, Jales LC, Camparis CM, Bigal ME. Temporomandibular symptoms, migraine, and chronic daily headaches in the population. Neurology. 2009;73(8):645–646. doi:10.1212/WNL.0b013e3181b389c2 [CrossRef]
  24. Ballegaard V, Thede-Schmidt-Hansen P, Svensson P, Jensen R. Are headache and temporomandibular disorders related? A blinded study. Cephalalgia. 2008;28(8):832–841. doi:10.1111/j.1468-2982.2008.01597.x [CrossRef]
  25. Bertoli FM, Antoniuk SA, Bruck I, Xavier GR, Rodrigues DC, Losso EM. Evaluation of the signs and symptoms of temporomandibular disorders in children with headaches. Arq Neurop-siquiatr. 2007;65(2A):251–255.
  26. Liljeström MR, Aromaa M, Bell YL, Jämsä T, Helenius H, Virtanen R, Anttila P, Metsähonkala L, Rautava P, Alanen P, Sillanpää M. Familial occurrence of signs of temporomandibular disorders in headache children and their mothers. Acta Odontol Scand. 2007;65(3):134–140. doi:10.1080/00016350601106165 [CrossRef]
  27. Lambourne C, Lampasso J, Buchanan WC Jr, Dunford R, McCall W. Malocclusion as a risk factor in the etiology of headaches in children and adolescents. Am J Orthod Dentofacial Orthop. 2007;132(6):754–761. doi:10.1016/j.ajodo.2006.03.033 [CrossRef]
  28. Heir GM. Facial pain of dental origin—a review for physicians. Headache. 1987;27(10):540–547. doi:10.1111/j.1526-4610.1987.hed2710540.x [CrossRef]
  29. Dodick DW, Eross EJ, Parish JM, Silber M. Clinical, anatomical, and physiologic relationship between sleep and headache. Headache. 2003;43(3):282–292. doi:10.1046/j.1526-4610.2003.03055.x [CrossRef]
  30. Rains JC, Poceta JS, Penzien DB. Sleep and headaches. Curr Neurol Neurosci Rep. 2008;8(2):167–175. doi:10.1007/s11910-008-0027-9 [CrossRef]
  31. Bruni O, Galli F, Guidetti V. Sleep hygiene and migraine in children and adolescents. Cephalalgia. 1999;19Suppl 25:57–59.
  32. Hering-Hanit R, Gadoth N. Caffeine-induced headache in children and adolescents. Cephalalgia. 2003;23(5):332–335. doi:10.1046/j.1468-2982.2003.00576.x [CrossRef]
  33. Dhuna A, Pascual-Leone A, Belgrade M. Cocaine-related vascular headaches. J Neurol Neurosurg Psychiatry. 1991;54(9):803–806. doi:10.1136/jnnp.54.9.803 [CrossRef]
  34. Satel SL, Gawin FH. Migrainelike headache and cocaine use. JAMA. 1989;261(20):2995–2996. doi:10.1001/jama.261.20.2995 [CrossRef]
  35. Heckerling PS, Leikin JB, Maturen A, Perkins JT. Predictors of occult carbon monoxide poisoning in patients with headache and dizziness. Ann Intern Med. 1987;107(2):174–176.
  36. Eberhardt M, Powell A, Bonfante G, et al. Non-invasive measurement of carbon monoxide levels in ED patients with headache. J Med Toxicol. 2006;2(3):89–92. doi:10.1007/BF03161015 [CrossRef]
  37. Hampson NB, Hampson LA. Characteristics of headache associated with acute carbon monoxide poisoning. Headache. 2002;42(3):220–223. doi:10.1046/j.1526-4610.2002.02055.x [CrossRef]
  38. Papanikolaou NC, Hatzidaki EG, Belivanis S, Tzanakakis GN, Tsatsakis AM. Lead toxicity update. A brief review. Med Sci Monit. 2005;11(10):RA329–RA336.
  39. Ferrari A. Headache: one of the most common and troublesome adverse reactions to drugs. Curr Drug Saf. 2006;1(1):43–58. doi:10.2174/157488606775252610 [CrossRef]
  40. Ferrari A, Spaccapelo L, Gallesi D, Sternieri E. Focus on headache as an adverse reaction to drugs. J Headache Pain. 2009;10(4):235–239. doi:10.1007/s10194-009-0127-1 [CrossRef]
  41. Dodick D, Freitag F. Evidence-based understanding of medication-overuse headache: clinical implications. Headache. 2006;46Suppl 4: S202–S211. doi:10.1111/j.1526-4610.2006.00604.x [CrossRef]
  42. Torelli P, Evangelista A, Bini A, Castellini P, Lambru G, Manzoni GC. Fasting headache: a review of the literature and new hypotheses. Headache. 2009;49(5):744–52. doi:10.1111/j.1526-4610.2009.01390.x [CrossRef]
  43. Wilson MH, Newman S, Imray CH. The cerebral effects of ascent to high altitudes. Lancet Neurol. 2009;8(2):175–191. doi:10.1016/S1474-4422(09)70014-6 [CrossRef]
  44. Moreau T, Manceau E, Giroud-Baleydier F, Dumas R, Giroud M. Headache in hypothyroidism. Prevalence and outcome under thyroid hormone therapy. Cephalalgia. 1998;18(10):687–689. doi:10.1046/j.1468-2982.1998.1810687.x [CrossRef]
  45. Tepper DE, Tepper SJ, Sheftell FD, Bigal ME. Headache attributed to hypothyroidism. Curr Pain Headache Rep. 2007;11(4):304–309. doi:10.1007/s11916-007-0208-2 [CrossRef]
  46. Shaikh MG, Wickramasuriya N, McLachlan K, Stirling H, Kirk JM. Thyroxine: cause and cure for headache. Acta Paediatr. 2006;95(5):632–633. doi:10.1080/080352500525327 [CrossRef]
  47. Kollars J, Zarroug AE, van Heerden J, et al. Primary hyperparathyroidism in pediatric patients. Pediatrics. 2005;115(4):974–980. doi:10.1542/peds.2004-0804 [CrossRef]
  48. Aamodt AH, Stovner LJ, Langhammer A, Hagen K, Zwart JA. Is headache related to asthma, hay fever, and chronic bronchitis? The Head-HUNT Study. Headache. 2007;47(2):204–212. doi:10.1111/j.1526-4610.2006.00597.x [CrossRef]
  49. Cai S, Hamiwka LD, Wirrell EC. Periictal headache in children: prevalence and character. Pediatr Neurol. 2008;39(2):91–96. doi:10.1016/j.pediatrneurol.2008.05.012 [CrossRef]
  50. Haas RH, Parikh S, Falk MJ, Saneto RP, Wolf NI, Darin N, Cohen BH. Mitochondrial disease: a practical approach for primary care physicians. Pediatrics. 2007;120(6):1326–1333. doi:10.1542/peds.2007-0391 [CrossRef]
  51. Sparaco M, Feleppa M, Lipton RB, Rapoport AM, Bigal ME. Mitochondrial dysfunction and migraine: evidence and hypotheses. Cephalalgia. 2006;26(4):361–372. doi:10.1111/j.1468-2982.2005.01059.x [CrossRef]
  52. Zaki EA, Freilinger T, Klopstock T, et al. Two common mitochondrial DNA polymorphisms are highly associated with migraine headache and cyclic vomiting syndrome. Cephalalgia. 2009;29(7):719–728. doi:10.1111/j.1468-2982.2008.01793.x [CrossRef]
  53. Niebanck AE, Pollock AN, Smith-Whitley K, et al. Headache in children with sickle cell disease: prevalence and associated factors. J Pediatr. 2007;151(1):67–72, 72.e1. doi:10.1016/j.jpeds.2007.02.015 [CrossRef]
  54. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004;24Suppl 1:9–160.
  55. Duzova A, Bakkaloglu A. Central nervous system involvement in pediatric rheumatic diseases: current concepts in treatment. Curr Pharm Des. 2008;14(13):1295–1301.
  56. Hershfield NB. Nongastrointestinal symptoms of irritable bowel syndrome: an office-based clinical survey. Can J Gastroenterol. 2005;19(4):231–234.
  57. Aamodt AH, Stovner LJ, Hagen K, Zwart JA. Comorbidity of headache and gastrointestinal complaints. The Head-HUNT Study. Cephalalgia. 2008;28(2):144–151.
  58. Zelnik N, Pacht A, Obeid R, Lerner A. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004;113(6):1672–1676. doi:10.1542/peds.113.6.1672 [CrossRef]
  59. Gabrielli M, Cremonini F, Fiore G, et al. Association between migraine and Celiac disease: results from a preliminary case-control and therapeutic study. Am J Gastroenterol. 2003;98(3):625–629. doi:10.1111/j.1572-0241.2003.07300.x [CrossRef]
  60. Borgna-Pignatti C, Fiumana E, Milani M, Calacoci M, Soriani S. Celiac disease in children with migraine. Pediatrics. 2004;114(5):1371. doi:10.1542/peds.2004-1337 [CrossRef]
  61. Alehan F, Ozçay F, Erol I, Canan O, Cemil T. Increased risk for coeliac disease in paediatric patients with migraine. Cephalalgia. 2008;28(9):945–949. doi:10.1111/j.1468-2982.2008.01630.x [CrossRef]
  62. Lionetti E, Francavilla R, Maiuri L, et al. Headache in pediatric patients with celiac disease and its prevalence as a diagnostic clue. J Pediatr Gastroenterol Nutr. 2009;49(2):202–207. doi:10.1097/MPG.0b013e31818f6389 [CrossRef]
  63. Smitherman TA, Baskin SM. Headache secondary to psychiatric disorders. Curr Pain Headache Rep. 2008;12(4):305–310. doi:10.1007/s11916-008-0051-0 [CrossRef]

Conditions Associated with IIH3,4

Obstruction of Venous DrainageCerebral venous sinus thrombosis
Brachiocephalic vein thrombosis
Increased right heart pressure
Endocrine DisordersAddison’s disease
Hypoparathyroidism
Thyroid replacement
Exogenous AgentsCorticosteroids (particularly withdrawal)
Growth hormone
Levothyroxine
Cytarabine, cyclosporine
Lithium
Levonorgestrel (Norplant)
Sulfa antibiotics
Tetracycline antibiotics (minocycline, doxycycline)
Vitamin A
Cis-retinoic Acid (Accutane)
Infectious ConditionsHIV infection
Lyme disease
Post-varicella
Other Medical ConditionsAnemia (sickle cell disease, iron deficiency, acquired aplastic anemia)
Antiphospholipid antibody syndrome
Behcet’s disease
Occult craniosynostosis
Sarcoidosis
Sleep apnea
Systemic lupus erythematosus

Secondary Causes of Acute Headache

Proportion of Disease Contribution to Acute Headache in ER (%)
Viral illness40% to 70%
Sinusitis1% to 16%
Posttraumatic headache5% to 7%
Meningitis/encephalitis2% to 9%
Streptococcal pharyngitis5% to 10%
Brain tumor2% to 3%
Postictal headache1% to 4%
Intracranial hemorrhage1%
Sinus venous thrombosis< 1%
Ischemic stroke< 1%
Intracranial cyst rupture< 1%
VP shunt malfunction< 1%

Medications that Cause Headache

Medications that Cause Headache in a Predictable, Dose-dependent Fashion Related to its Mechanism of ActionACE inhibitorsMethylxanthinesAlpha- and beta-adrenergic agonists and blockersNitratesAmphetaminesPhosphodiesterase (PDE) inhibitorsAntiarrhythmicsSympathomimeticsCalcium-channel blockers
Medications that Cause Headache when WithdrawnCaffeineEstrogenErgotamineOpioids
Medications that Cause Headache Idiosyncratically, and/or Cause Aseptic MeningitisAcid blockers, including famotidine and ranitidineAntimicrobials, including amoxicillin, metronidazole, sulfamethoxazole, trimethoprimImmune globulinNonsteroidal anti-inflammatory medications, including ibuprofen, ketorolac, naproxen
Medications that Cause Headache after Chronic Use and/or Cause Increased ICPAmiodaroneAntimicrobials, including ciprofloxacin, gentamicin, nitrofurantoin, ofloxacin, tetracyclineHormonal agents, including corticosteroids, oral contraceptives, thyroid hormone replacementVitamin A and retinoic acid

CME Educational Objectives

  1. Delineate the differential diagnosis of headache in children beyond common tension headache and migraine.

  2. Identify the pathophysiology and presenting symptoms of increased intracranial pressure.

  3. Explain the key clinical features for the more common secondary causes of headache in children.

Authors

Heidi Blume, MD, MPH, is Assistant Professor, Division of Pediatric Neurology, Seattle Children’s Hospital. Christina L Szperka, MD, is Resident in Neurology, Hospital of the University of Pennsylvania and Children’s Hospital of Philadelphia.

Dr. Blume and Dr. Szperka have disclosed no relevant financial relationships.

Address correspondence to: Heidi Blume, MD, MPH; fax: 206-987-2649; e-mail .heidi.blume@seattlechildrens.org

10.3928/00904481-20100623-10

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