International Classification of Headache Disorders 4: Classification committee comments on differentiating primary from secondary headache and recognizing “medication overuse”

The Classification Committee discussed the issues that arise due to the phenotypic overlap of primary and secondary headache disorders. The Committee sought to expand upon the comments in the section How to use this Classification (paragraph 9) since the matter is of considerable pathophysiological and clinical significance (1). Although we recognize this can be of concern across a range of primary headache phenotypes, we highlight phenotypic migraine here, to exemplify the broader issues. We discussed several secondary headache disorders that can have migraine-like phenotypes and/or commonly co-occur with migraine including post-traumatic headache, medication-overuse headache, and conditions that can temporarily exacerbate migraine, such as systemic infections (2–4).

We consider the following circumstances (Table 1), using migraine as an exemplar primary headache disorder and post-traumatic headache as an exemplar secondary headache disorder:

Pure secondary headache. In the absence of a prior history of headache, a de novo headache disorder arises in close temporal relation (e.g., within seven days) or logical causal relation following a potentially etiologic event, disease, or condition, with the biological potential to cause headache. Ideally, if the initiating event or cause is removed, the headache disorder will improve or remit, as specified in ICHD-2, but not in ICHD-3 (1,5). However, headache does not always remit when the secondary factor is eliminated. This may be due to persistent injurious consequences of the inciting event or the inability to eliminate the causal factor, which may have caused permanent damage.

Table 1.

Differentiating primary from secondary headache.

	Pure Secondary Headache	Exacerbation of Pre-Existing Headache	Onset Secondary Headache + Pre-Existing Headache
Antecedent Headache	No	Yes	Yes
Antecedent Headache Increases in Frequency and/or Intensity After Inciting Event	N/A	Yes	Yes/No
Antecedent Headache Changes in Fundamental Headache Characteristics (not only frequency/intensity) and/or Associated Symptoms After Inciting Event	N/A	No	Yes

Note: “Pure Secondary Headache,” “Exacerbation of Pre-Existing Headache,” and “Onset of Secondary Headache with Continuation of Pre-Existing Headache” are differentiated using three key features included in the table. “Antecedent Headache” refers to a headache disorder that is present prior to exposure to an event, disease, or condition that can cause a secondary headache or exacerbate a primary headache. N/A = not applicable

As an example, a “pure post-traumatic headache” occurs in the individual without an antecedent primary headache disorder who develops headache of a migraine phenotype within one day of a traumatic brain injury and has resolution of post-traumatic headache within two weeks of onset.

For ostensibly “pure secondary headache,” a problem is that the potential etiologic event may have initiated migraine in an individual who was genetically or physiologically predisposed. Alternatively, incident migraine may have occurred due to natural history, and the potentially inciting event may be a red herring. Requiring a close temporal relationship between the inciting event and headache onset reduces the likelihood that the new headache is incident migraine.

2.Exacerbation of pre-existing headache by a specific event, disease, or condition. In this setting, a person with pre-existing headache is exposed to an event, disease, or condition with the biological potential to cause headache and then has an increase in headache frequency or severity without a change in headache characteristics or associated features. The change in headache pattern represents an exacerbation of the pre-existing headache disorder. This designation is favored if the symptom profile of headache changes in frequency or severity without an out of proportion change in other fundamental characteristics or associated symptoms, and if the exacerbation subsides when the event, disease or condition is removed.

As an example, an “exacerbation of migraine by a mild traumatic brain injury” occurs in an individual who typically experiences one migraine attack per week, but within the week following a mild traumatic brain injury experiences three migraine attacks with characteristics that are unchanged compared to their pre-existing migraine attacks. After one week, their migraine attack frequency returns to baseline. This individual is diagnosed with migraine. They are not diagnosed with post-traumatic headache.

3.Onset of a secondary headache in a person with pre-existing headache. In this situation, the person has a headache disorder prior to an inciting event and then a superimposed de novo headache disorder arises following a potentially etiologic event, disease, or condition, with the biological potential to cause a headache. This designation is favored if the new type of headache differs in quality or associated symptom profile from the antecedent primary headache profile.

A case example of “onset of post-traumatic headache in a person with pre-existing migraine” is the person who typically experiences weekly migraine attacks that always include visual aura, photophobia, phonophobia, and nausea, and headaches that are moderate to severe intensity, unilateral, throbbing, and frontally located. Starting on the day following a mild traumatic brain injury, the person develops a continuous, holocephalic, pressure sensation, mild to moderate intensity headache that is not associated with photophobia, phonophobia, or nausea. These new headaches persist for a few weeks. This person is diagnosed with migraine with aura and acute post-traumatic headache attributed to mild traumatic brain injury.

Of course, this exercise could be repeated with other types of secondary headaches. For example, it is now clear that headache is a manifestation of COVID-19 infection. We could have “pure secondary headache attributed to COVID-19” in circumstance #1, “exacerbation of migraine by COVID-19” in circumstance #2, and dual diagnoses of “secondary headache attributed to COVID-19” and “migraine” in circumstance #3.

The Classification Committee's discussion about medication-overuse headache also included the need to recognize medication overuse in the absence of medication-overuse headache. In this context, medication overuse indicates that the patient takes medications that can be used for the acute treatment of migraine attacks at a frequency that exceeds the “overuse” thresholds included in the ICHD-3 diagnostic criteria for medication-overuse headache (1). The term “medication overuse” is intended to be etiologically agnostic since, in many patients, we do not know if increasing headache drives increasing medication taking, or if increased medication intake drives increasing headache frequency, or both. Furthermore, medication overuse can be present in those with episodic headache, such as episodic migraine (6), and recognition of medication overuse is an indicator that headache preventive approaches need optimization to avoid transition to chronic headache and development of medication-overuse headache. Recognizing medication overuse, even when medication-overuse headache may not be present, allows medication overuse to be addressed and treated without the need to demonstrate causal attribution between medication intake and onset of a new headache type (i.e., medication-overuse headache).

The Committee plans to consider further whether the terms “medication overuse” and “medication-overuse headache” are pejorative and if there are better terms to be used in the ICHD-4.