Tumor-Related Headache: Path to Diagnosis, Treatment Isn't Always Obvious

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Headaches are a common occurrence in the general population and are often present in patients with an underlying brain tumor. <i>Credit:Living Art Enterprises/Science Source</i>
Headaches are a common occurrence in the general population and are often present in patients with an underlying brain tumor. Credit:Living Art Enterprises/Science Source

Headaches are a common occurrence in the general population and are often present in patients with an underlying brain tumor, although it is not yet clear to what degree they are related.1 Contrary to conventional thinking, however, headache associated with a brain tumor may be essentially the same as headache without a brain tumor. The International Classification of Headache Disorders-3 (ICHD-3) definition of classic "brain-tumor headache" may not capture the broad range of headache presentations observed in patients with brain tumors.1,2

ICHD-3 Description and Diagnostic Criteria for Headache Attributed to Intracranial Neoplasm2:

  • Progressive headache
  • Worse pain in the morning
  • Aggravated by Valsalva-like maneuvers
  • Space-occupying intracranial neoplasm has been demonstrated
  • Causation demonstrated by 2 of the following:
    1. Headache development in temporal relation to development of the neoplasm, or led to its discovery
    2. Worsening headache in line with worsening neoplasm
    3. Headache improvement with successful treatment of neoplasm

In a 2014 review, Lynne P. Taylor, MD, found that primary headache disorders and headaches secondary to brain tumors often share a common pathology.3 Although the mechanisms are not yet understood, evidence that treatment of the primary tumor often resolves the headache suggested that structural changes and increased intracranial pressure associated with the presence of a space-occupying lesion are the main causes. Other secondary effects from a tumor, including neuroinflammation and increased sensitization of peripheral and central regions of the brain, may also contribute to headache pain.3

Despite this, Dr Taylor, from the University of Washington Medical Center, Seattle Cancer Care Alliance, and codirector of the Alvord Brain Tumor Center in Seattle, Washington, found that brain tumor headache is not as common as originally thought, and that the most important risk factor is a preexisting headache disorder.3 "From the perspective of neuro-oncology, we believe that there has been an unfortunate overemphasis on the classic 'brain tumor headache,' " she said, noting that in her review, she found that morning headache was only present approximately 32% of the time, and that the "red flag" headache that wakes someone in the middle of the night is actually quite rare.3

In an interview with Neurology Advisor, Dr Taylor emphasized that it is personality changes, not headaches, that are the most frequent presenting symptom of a brain tumor. "In general, especially given access to [computed tomography] and brain [magnetic resonance imaging] scans, headache is much less likely to be a sign of a tumor now than in the past," she said, citing studies reporting only an 8% to 12% incidence of isolated headache as a sole symptom of brain tumor.4,5

Headache specialist Peter McAllister, MD, medical director, New England Institute for Neurology and Headache, and chief medical officer for the New England Institute for Clinical Research and Ki Clinical Research in Stamford, Connecticut, agreed. "Although any significant change in a headache pattern should prompt consideration of a secondary headache such as a tumor, only about 40% of tumors have headache pain as a predominant symptom," he said.

Miles J. Levy, consulting endocrinologist to University Hospitals of Leicester NHS Trust in the United Kingdom, told Neurology Advisor that "typically, worrying causes of intracranial headache are associated with other focal neurological symptoms such as behavior change, 1-sided weakness, or sensory disturbance, seizures, etc."

Differentiating Primary vs Secondary Headache

It is frequently not possible to differentiate a primary headache from 1 that is secondary to a brain tumor, Dr Taylor said, "as the most common presentation of tumor-related headache is identical to a migraine headache. Progressive headache is probably the most important sign of a tumor, especially if it is coupled with new or progressive sensory or motor symptoms or personality changes," she noted.

Although headaches that change in severity or location point to a tumor-related headache, Dr McAllister emphasized that in clinical practice, primary headaches are much more common that tumor-related ones, and in someone with a history of migraine, "even with a change in headache pattern of severity, the most likely diagnosis is still migraine." When a tumor-related headache does present, he said, "usually the pain is dull, mild to moderate in severity and stays in 1 spot, and is often associated with other symptoms such as change in mentation, seizure, or 1-sided numbness or weakness."

Types of Tumors Associated With Headaches

Three main types of tumors have been associated with headache symptoms, including pituitary tumors (in both benign and malignant forms), meningiomas, and glioblastoma multiforme, the most common brain malignancy.

In a review of pituitary tumors and headache, Dr Levy found that even when neuroimaging shows the presence of a pituitary lesion, it may still be unclear whether the presenting headache is related.6 Although "small incidental pituitary lesions are present in approximately 10% of the population," he wrote, the presence of concomitant headaches is more commonly a result of a primary headache disorder.6

"We found that pituitary tumors can cause many types of headaches, including rare phenotypes that have cranial autonomic features," Dr Levy explained.6,7 "These are not necessarily related to size of the tumor, and the cavernous sinus may play a role. With pituitary lesions, it may be the hormonal activity also which plays a role; for example, growth hormone-secreting pituitary tumors may cause bad headache that responds to certain medications."

Dr Taylor added, "There is a unique group of tumors in the orbit and pituitary gland that can involve the trigeminal vascular system and produce a different type of headache than the pressure-like headache associated with a large space-occupying tumor. This type of a headache includes cluster headache and paroxysmal hemicranias."

Managing Tumor-Related Headaches

Although treating the primary tumor may eliminate the headache, this is not always the case, and headache treatment may continue after the tumor is removed or reduced by surgical excision or drug therapy. As Dr Levy pointed out, "Whether headache improves with treatment depends on whether it is primary headache (in a patient predisposed to headache) or entirely secondary (related to the pathology). Not uncommonly, it is a bit of both."

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References

  1. Nelson S, Taylor LP. Headaches in brain tumor patients: primary or secondary?Headache. 2014;54:776-785.
  2. Headache Classification Subcommittee of the International Headache Society. The International classification of headache disorders, 3rd edition (beta version). Cephalalgia. 2013;33:629-808.
  3. Taylor LP. Mechanism of brain tumor headache. Headache. 2014;54:772-775.
  4. Vazquez-Barquero A, Ibanez FJ, Herrera S, et al. Isolated headache as the presenting clinical manifestation of intracranial tumors: A prospective study. Cephalalgia. 1994;14:270-272.
  5. Bioardi A, Salmaggi A, Eoli M, et al. Headache in brain tumours: A symptom to reappraise critically.Neurol Sci. 2004;25:S143-S147.
  6. Levy MJ. The association of pituitary tumors and headache.Curr Neurol Neurosci Rep. 2011; 11:164-170.
  7. Levy MJ, Matharu M, Goadsby PJ. Chronic headache and pituitary tumors. Curr Pain Headache Rep. 2008;12:74-78.
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