Teenager With Chronic Daily Headache of Sudden Onset

June 1, 2006

A 15-year-old boy complains of moderate to severe headaches that occur daily and usually last all day; the pain typically worsens toward the end of the day. How will you help this patient?

A 15-year-old boy complains of moderate to severe headaches that occur daily and usually last all day; the pain typically worsens toward the end of the day. The headache is bilateral and involves the forehead, temporal areas, and occipital areas.The pain of his moderate headaches (4 or 5 on a 10-point visual analog scale) is dull and continuous. Two or 3 times a week, he has 2- to 6-hour episodes of severe head pain (7 or 8 on a 10-point scale--it almost never reaches 10). These he describes as a feeling of pressure with throbbing.During a severe headache, he occasionally experiences mild nausea, without vomiting, and increased sensitivity to bright light and loud noise. The severe episodes exhibit no regular pattern, and he cannot identify any triggering or exacerbating factors. The patient takes ibuprofen or acetaminophen 2 or 3 times a week for management of the severe headaches, but he does not use any medication for the milder headaches.The patient easily recalls the time 3 years earlier when the headaches started. His parents note that 2 weeks before the headaches began, he had flu-like symptoms (fever, sore throat, decreased appetite, and fatigue) and enlarged lymph nodes in the neck area. After 1 week of symptomatic therapy, the fever and sore throat resolved; the weakness, fatigue, and headaches continued for another 2 to 3 months. After that, only the headaches remained, and they have occurred daily since they started. He had no previous history of headaches.Results of a physical examination are unremarkable. Laboratory results include evidence of IgG for Epstein-Barr virus (EBV) but no evidence of IgM for EBV. The results of a CT scan of the sinuses and of an MRI of the brain are normal.

  • What is the differential diagnosis of chronic daily headache?

  • Which features of the history are most helpful in pinpointing the diagnosis?

  • What should be the primary focus of therapy for this patient?


Primary care doctor: This patient has chronic daily headache of sudden onset and 3 years' duration, along with serologic evidence of remote EBV infection. What features here point to a diagnosis?

Headache specialist: The sudden onset of the headachesand the absence of other factors that might contributeto his condition (no abnormalities on physical examination,sinus CT, or brain MRI) suggest new daily persistentheadache (NDPH).

Primary care doctor: What are the diagnostic criteria for NDPH?

Headache specialist: According to the second edition ofthe International Headache Society's Classification ofHeadache Disorders, NDPH is a chronic, unremittingdisorder of sudden onset and a daily pattern that is presentfrom the first day or that develops within 3 days ofonset.1 Usually, patients can easily identify the time ofheadache onset with impressive accuracy, as this patientdoes. The chronic pattern should persist for at least 3months. Other helpful features are the moderate severity,bilateral location, and dull tightening quality of thepain. However, some migraine-like features, such asthrobbing, may also be present, although obvious triggerfactors (eg, physical exertion, routine activities) arenot found and associated symptoms (nausea, photophobia, and phonophobia) are mild. Vomiting is almost alwaysabsent.

Primary care doctor: In a patient who presents with achronic throbbing headache, how would you differentiatebetween NDPH and status migrainosus?

Headache specialist: Both status migrainosus, which isdefined as a migraine that lasts longer than 72 hours,and NDPH begin abruptly. Distinguishing between thetwo may be difficult when the disorder is in its beginningstages. However, status migrainosus possesses allmigraine features: throbbing quality; severe pain; andassociated nausea, vomiting, and extreme sensitivity tobright light and loud noise. Typically, status migrainosusis a disabling condition; vomiting is common andfrequently causes severe dehydration and electrolyte imbalancesthat require urgent hospitalization.

Here, although some migraine-like features (eg,throbbing) are present, the patient is able to continuehis regular daily activities, such as attending school. Theheadache does adversely affect his life, but he is notcompletely disabled. The pain is moderate, vomiting isabsent, and the other associated symptoms are not aspronounced as those observed in patients with status migrainosus.Also, although status migrainosus lasts longerthan 72 hours, it never persists for 3 years. In the majorityof patients with status migrainosus, the duration is limitedto 1 or 2 weeks. In sum, status migrainosus is an extremeand prolonged presentation of migraine.

Primary care doctor: What about transformed, or chronic,migraine? How would you differentiate NDPH fromtransformed migraine?

Headache specialist: The clinical presentation alonedoes not provide sufficient information to establishthe diagnosis. Both types of headache may be bilateralor involve the entire head. Patients with either typeof headache may describe the pain as moderate tosevere and throbbing. Both disorders are chronic,and affected patients may complain of mild associatedsymptoms.

This patient can easily recall the date of onset of hisdaily headaches. He also has no prior headache history,and the daily headache pattern did not vary after itsonset. All of these factors perfectly "fit" the definition ofNDPH. In contrast, patients with transformed migraineusually report a history of episodic migraine that precedesthe transformation period, during which a gradualincrease in frequency is observed. Many patients withtransformed migraine find it difficult to recall when theheadache became chronic.

Primary care doctor: How often do you see patients withNDPH?

Headache specialist: Not often, although we do seesome variation in the prevalence of NDPH among differentage groups. According to some studies, the prevalenceof NDPH in pediatric populations varies between12% and 23% of all children with chronic dailyheadaches.2,3 In an adult population with chronicheadaches, NDPH occurred half as often as it did inthese younger patients. The mean age at onset of thedisorder is 34.8 years.4

Primary care doctor: What factors contribute to the developmentof NDPH?

Headache specialist: The exact cause has not yet beenestablished. In 1 study, the cause was unknown in 80%of patients, while in the other 20%, emotional stress wasfound to be a triggering factor.5 Another study pointedto a viral origin for NDPH in many patients, with serologicfindings suggestive of recent infection with herpessimplex virus in 42% of patients and evidence of Cytomegalovirusinfection in 11%.6 In the same study, no evidenceof infection with EBV was found.6

However, the most consistent findings regardingthe cause of NDPH suggest that EBV in particular mayplay a significant role in its development.7,8 In somestudies, an infectious disease had been diagnosed at theonset of NDPH in more than 40% of patients who hadthe condition. In more than half of those patients inwhom an infectious disease was diagnosed, serologicfindings suggested recent EBV infection.3 The percentageof patients with NDPH who are serologically positivefor EBV infection may be as high as 84%, with 62%actively excreting EBV from the oropharynx.8

Primary care doctor: What is the recommended treatmentfor NDPH, and what is the prognosis for affectedpatients?

Headache specialist: When treating patients with achronic headache disorder, use a multidisciplinary approachthat combines pharmacotherapy and nonpharmacologicmethods. The most important aspect ofNDPH treatment is prevention. A variety of agents canhelp prevent headaches in patients with NDPH, includingtricyclic antidepressants (TCAs), β-blockers, calciumchannel blockers, anticonvulsants, and monoamineoxidase inhibitors (MAOIs). We recommend TCAs asfirst-line therapy. Start with protriptyline in patients whodo not have significant sleeping difficulties; considerdoxepin or nortriptyline in patients who present withboth NDPH and insomnia. β-Blockers or calcium channelblockers may be used in combination with TCAs.Second-line therapy includes various anticonvulsants.Finally, if a patient is refractory to all these agents, considerusing an MAOI. Various abortive medications,such as triptans or ergotamine-containing agents, maybe used to control severe exacerbations.

Pharmacologic therapy alone is not as effectiveas approaches that also incorporate nonpharmacologicmethods. Thus, in addition to medical treatment,it is prudent to refer patients for therapies such asbiofeedback, relaxation techniques, or counseling.However, even with combination therapy, 50% or moreof patients with NDPH may not achieve a successfulresolution.6


International Headache Society. International Classification of Headache Disorders, 2nd ed. Cephalalgia. 2004;24(suppl 1):8-160.
Moore AJ, Shevell M. Chronic daily headaches in pediatric neurology practice. J Child Neurol. 2004;19:925-929.
Mack KJ. What incites new daily persistent headache in children? Pediatr Neurol. 2004;31:122-125.
Bigal ME, Lipton RB, Tepper SJ, et al. Primary chronic daily headache and its subtypes in adolescents and adults. Neurology. 2004;63:843-847.
Takase Y, Nakano M, Tatsumi C, et al. Clinical features, effectiveness of drug-based treatment, and prognosis of new daily persistent headache (NDPH): 30 cases in Japan. Cephalalgia. 2004;24:955-959.
Meineri P, Torre E, Rota E, et al. New daily persistent headache: clinical and serological characteristics in a retrospective study. Neurol Sci. 2004;25(suppl 3):S281-S282.
Hamada T, Ohshima K, Ide Y, et al. A case of new daily persistent headache with elevated antibodies to Epstein-Barr virus. Jpn J Med. 1991;30:161-163.
Diaz-Mitoma F, Vanast WJ, Tyrrell DL. Increased frequency of Epstein-Barr virus excretion in patients with new daily persistent headaches. Lancet. 1987;21:411-415.


  • Evans RW. New daily persistent headache. Curr Pain Headache Rep. 2003;7:303-307.