Current Pain and Headache Reports

, Volume 16, Issue 4, pp 287–288

Expert Commentary–Unusual Headache Syndromes


    • Head of the Merck Investigator Study Program, Scientific Engagement and Education (MISP/SEE), Office of the Chief Medical Officer-Merck
Invited Commentary

DOI: 10.1007/s11916-012-0266-y

Cite this article as:
Bigal, M.E. Curr Pain Headache Rep (2012) 16: 287. doi:10.1007/s11916-012-0266-y

There is no disease so rare

that it does not deserve attention.

Rare diseases are rare,

but rare disease patients are numerous [1].

Headache medicine may be an arduous field. While identifying and treating common headache disorders is often not difficult, so many medical conditions may present with headache as the first or chief complaint that the differential diagnosis of patients with headache may be overwhelming [2].

The most common headache syndromes are primary headaches. They typically do not impose major diagnostic challenges, although they are not always easy to treat. In the primary headaches, headache is the “disease” itself. Failure to identify and to properly treat a primary headache will cause unnecessary burden to the patient [36]. As for the secondary headaches, the headaches are the symptom of another disease. The situation is very different. Failure to identify a secondary disease may represent a very ominous situation. Not only may the patient face unnecessary suffering, but more concerning, a treatable condition may be missed until it is too late [7, 8].

Though conceptually simple, diagnosing secondary headaches is indeed a difficult task. Secondary headaches often mimic chronic daily headache (CDH), a primary headache disorder, but are very frequently truly uncharacteristic. Nonetheless, patients with intractable headache often live with both the hope and the fear that the doctor “missed something.” This is also a concern for clinicians who care for patients with difficult to manage headaches. Because the issue is indeed overwhelming, reductionism happens (“it should be CDH or a refractory primary headache”). However, although unusual in isolation, the “unusual headache syndromes” become sizeable if considered as a group. The current issue of Current Pain and Headache Reports presents five unique papers that help to shed light on the topic and herein we add our perspective.

A few years ago, a group of headache experts decided to approach the topic of the unusual headache syndromes under the scope of “why treatment of headache fails” [9, 10]. As with anything else, we felt that a systematic approach to treatment failure would decrease the chances of persistent failure. We collected reasons into five major groups: (1) diagnosis is incomplete or incorrect; (2) important exacerbating factors have been missing; (3) pharmacotherapy is inadequate; (4) non-pharmacological strategies have been neglected; and (5) miscellany (unrealistic expectations, fail to diagnose comorbidities, etc).

Under the first reason (diagnosis is incomplete or incorrect), we subdivided the group into three possibilities: (A) a secondary headache disorder goes undiagnosed; (B) a primary headache disorder is misdiagnosed; and (C) more than one headache is present and only one is diagnosed. Herein I will present a few comments that we offered for the discussion that is germane to this issue of the journal (focusing on when a secondary disorder or unusual syndrome is undiagnosed).

When facing a patient with atypical presentation or refractory to medications, it is useful to focus on the temporal profile of the headache, since it can provide important clues to its etiology. For example, a rapid-onset headache may suggest a subarachnoid hemorrhage, pituitary apoplexy, or other intracranial catastrophes. Rapid-onset headache also can be acute-onset migraine. Sphenoid sinusitis may cause a subacute intractable headache and may be missed radiologically unless appropriate studies are performed.

Headaches that start after age 55 suggest an organic disorder, such as a mass lesion or temporal arteritis. Giant cell arteritis (as discussed by Dr. Nahas in this issue) is often underdiagnosed and is an important cause of preventable blindness in the elderly.

Concurrent events and headache triggers may also give clues to diagnosis. For example, headaches that occur in the peripartum period may be due to dural sinus thrombosis; fever suggests an infectious etiology; orthostatic headache suggests a “low CSF pressure” headache which can result from a spontaneous CSF leak, a previous lumbar puncture, or an epidural block. Headache triggered by straining, coughing, or sneezing suggests a hindbrain malformation, occipitocervical junction disorder, or increased intracranial pressure. When headache is worse in the morning it may suggest raised intracranial pressure or sleep apnea—in contrast, when headache is better in the morning and worse at night it may suggest low CSF volume headache.

A skin rash suggests Lyme disease, herpes zoster, or sarcoidosis. Other dermatological disorders might suggest the presence of a systemic or localized disease, such as antiphospholipid syndrome, Sneddon’s syndrome, etc. It is often important to search for opportunistic infections, including toxoplasmosis and cryptococcal meningitis, in patients who may have human immunodeficiency virus (HIV) infection or HIV risk factors.

The history often neglects recent dental procedures such as root canal, tooth extractions, or bite disturbances that may provoke or be associated with the development of intractable headache due to brain abscess.

We too often neglect the importance of the general physical exam in the diagnosis of unusual headache syndromes. For example, symptoms of nasal blockage, drainage, pus, or pressure may suggest sinus disease. Nasopharyngeal carcinoma can produce chronic head and face pain and can be identified by detailed, expert examination of the nasopharynx or neuroimaging. Indeed the physical examination should focus on the systems that are important in headache provocation, such as eyes, ears, neck, and areas of trigeminal innervation. Examining the oral cavity health, and pain and discomfort in the temporomandibular joint area, may provide diagnostic clues, as detailed in the paper by Gonçalves et al. in the current issue of the journal.

Sometimes the headache is not characteristic and even a thorough physical exam is normal; therefore, proper diagnostic testing is required. Many patients with intractable headache have had multiple neuroimaging procedures. In these cases, one should consider studies targeted to suspected sites of pathology, including the occipitocervical junction, sella turcica (see paper by Bussone et al.), sphenoid sinus, and nasopharyngeal regions. For truly intractable patients who fail many therapies, a lumbar puncture is important to identify inflammatory or infectious changes that could indicate aseptic or chronic meningitis, as well as idiopathic intracranial hypertension (IIH)

The vast majority of refractory headache patients seem to have a biologically determined problem that has either been misdiagnosed, mistreated, or is simply very difficult to treat. Among those that are misdiagnosed, many have unusual headaches. At the risk of being redundant, unusual headaches are not that unusual when looked at collectively. Because of the range of potential differential diagnoses, a structured approach is useful. We may not know all the possibilities, but we should know how to order the clinical thinking by pragmatically following a structured approach. Crucial elements include a thorough history, supplemented by general medical and neurological examinations, as well as laboratory testing and neuroimaging in selected patients. If multiple headache disorders occur concurrently, the conceptual process needs to be repeated for each headache.


Dr. Marcelo Bigal is an employee of Merck & Co. and owns stock interest in the company.

Copyright information

© Springer Science+Business Media, LLC 2012