According to the National Institute of Neurological Disorders and Stroke, headache is the most commonly experienced form of pain.1 Of more than 150 types of headache listed in the International Classification of Headache Disorders (ICHD), tension-type headache (60%-80%) and migraine (15%) have the highest prevalence.2 Although other types of headache are much less common, an accurate diagnosis is essential to inform treatment strategy, particularly with headache that may be secondary to a potentially life-threatening medical condition.

In a March 2019 review published in the Medical Clinics of North America, investigators summarized evidence on nonmigraine headache and facial pain.3

Secondary headaches

Cervical artery dissection (CEAD) is a leading cause of ischemic stroke in young adults, for whom traditional risk factors are not the underlying etiology. Although CEAD is accompanied with symptoms similar to migraine or musculoskeletal pain, including headache and neck pain, patients typically have focal neurologic signs as well. “Dissection of the vertebral artery may result in cerebellar, brain stem (lateral medullary), or occipital lobe infarct, and dissection of the carotid artery may present with a partial Horner syndrome (ptosis and miosis) in addition to hemispheric strokes and dysautonomia,” noted the review authors.3

Migraine is one of the risk factors for CEAD, and people with migraine comprise one-third of cases of CEAD. Other risk factors include fibromuscular and connective tissue disorders and possibly recent infection or minor cervical trauma. “Pathognomonic radiodiagnostic findings include dissection flaps and ‘pearl-and-string’ sign.”3 Antiplatelet therapy is typically used to treat CEAD recurrence, and vascular surgery may be indicated in some cases.

Cerebral venous thrombosis is another cause of stroke that affects predominantly younger patients. The mean age of those with cerebral venoius thrombosis is 39 years, with women comprising an estimated 74% of these cases. Headache and seizure are present in 90% and 40% of cases of cerebral venous thrombosis, respectively.3 Other common clinical manifestations include paresis, papilledema, altered mental state, aphasia, diplopia, visual deficits, and stupor or coma.3,4 “Multiple venous sinuses are involved in almost half of cases, with the superficial veins of the superior sagittal sinus and transverse sinus most commonly involved,” noted the review authors.3

Risk factors include thrombophilia, pregnancy/puerperium, oral contraceptive use, malignancy, infection, and dehydration. Treatment is with intravenous heparin in most cases, and thrombectomy/thrombolysis may be warranted in severe cases. With mortality rates of 6% to 20%, treatment in a stroke center is ideal, as such interventions have been associated with a 14% reduction in mortality.3

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by alternating constriction and dilation of the cerebral arteries, with “thunderclap” headaches, a term that refers to severe and explosive headaches that reach maximal intensity within 1 minute of onset as the primary symptom. These headaches recur over a period of 1 to 3 weeks and may be accompanied by nausea, vomiting, photophobia, blurred vision, and confusion.3,5 Sexual activity, Valsalva maneuvers, and straining have been reported as triggers for these headaches in some cases.

“Although the disease is self-limiting, there is a high risk [for] neurologic sequelae from intracranial hemorrhage, infarction, or edema. Initial arterial imaging peaks 2 to 3 weeks after symptom onset, and as such, normal imaging on presentation should be repeated.”

Risk factors for RCVS include nonaneurysmal subarachnoid hemorrhage, neurosurgical procedures, puerperium, vasoactive drugs, and certain conditions such as pheochromocytoma and porphyria.5 In addition to supportive measures and discontinuation of any offending agent, calcium channel blockers are often used to prevent vasospasm in patients with RCVS.

The authors also describe headaches associated with impaired cerebrospinal fluid (CSF) dynamics such as intracranial hypertension and inflammatory conditions such as giant cell arteritis.

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Clinical Pain Advisor interviewed Nauman Tariq, MD, assistant professor of neurology at Johns Hopkins University School of Medicine and director of the Johns Hopkins Headache Center.

Clinical Pain Advisor: What are the most clinically relevant types of nonmigraine primary headache and facial pain?

Dr Tariq: Cluster headache is unique because it presents with cranial autonomic symptoms such as conjunctivitis, nasal congestion, rhinorrhea, and ptosis. This is a very severe headache that is usually focused around the periorbital region and is more common in men and smokers. The critical feature of cluster headache is that it is timed — its duration must be between 15 minutes and 3 hours or it is not classified as a cluster headache. Magnetic resonance imaging studies show activation in the same areas of the brain in cluster headache and migraine — the hypothalamus and midbrain. The hypothalamus has a major role in cluster headache — hence the cranial autonomic symptoms. This type of headache may be missed in a family medical setting and warrants referral to a headache center.

Trigeminal neuralgias present with sharp, stabbing face pain lasting a few seconds, followed by a refractory period without pain, and this cycle may repeat multiple times. As a unique feature, these are often associated with cutaneous triggers like brushing one’s teeth, shaving, and even cold wind on the face. Many of these patients have a neurovascular compression of the trigeminal nerve — which can demyelinate the nerve and cause pulsating pain — and frequently responds well to microvascular decompression. First-line medications include carbamazepine and oxcarbazepine.

Postconcussion headache has been an increasing focus of discussion in the literature and in the news over the past 2 years. Postconcussion headache can develop even in patients without a history of migraine, with lasting symptoms that resemble migraine symptoms. In a study of veterans with mild to moderate traumatic brain injury, 35% had persistent headache even 5 years after concussion.6

Hemicrania continua is a unique type of headache that is side locked, with the same autonomic symptoms as cluster headache. However, it is continuous, and not timed like cluster headache. These headaches are so rare that they can be misdiagnosed, sometimes for years. In the ICHD, the diagnostic criteria require that this headache must respond to indomethacin — if it does not, then you must consider another type of headache like cervicogenic headache. Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) with a chemical structure that is different from the other NSAIDs but similar to melatonin and with high CSF penetration. In practice, if an unusual headache does not fulfill the migraine criteria, we will often prescribe indomethacin for 2 to 3 weeks to see whether it responds.

Persistent idiopathic facial pain often occurs after a dental procedure, but it is very rare considering the number of dental procedures performed. I do think this phenomenon is underreported in the literature. In the last 5 years I have seen maybe 20 to 25 patients who have been unresponsive to all treatments. Patients may experience 30% to 40% relief from various treatments. In meetings, my colleagues and I persistently view this condition as a challenge. Once it becomes chronic, it is very hard to treat. It is a type of facial pain that does not respect the trigeminal branch boundaries. Compared with trigeminal neuralgias, which will affect one division or another, persistent idiopathic facial pain is sometimes diffuse all over the face. It would be helpful if clinicians would collect those cases for a larger cohort study. This may ultimately prompt larger studies to investigate biomarkers and try to identify predictors of persistent facial pain that is unresponsive to treatment.

Clinical Pain Advisor: What are some key takeaways for clinicians regarding this topic?

Dr Tariq: Accurate diagnosis is very important because we do not have biomarkers to distinguish among the different types of headache, as in the way troponin is used in cardiac care, for example. There is some preliminary progress in the research, but those studies are very small. Thus, we have to rely on those set criteria, and many times, adequate experience and training are required to pick up the less common types of headache.

When the physician in an outpatient clinic is dealing with an unusual type of headache, I recommend that they visit the ICHD website, which features straightforward diagnostic criteria for the range of headache types. If a patient does not respond after a couple of treatment trials, then refer the person to a neurologist or headache specialist.

Often, patients can improve significantly with treatment, but if they have to wait 4 to 5 years to receive an accurate diagnosis, that is a lot of time living with unnecessary symptoms and disability, and their prognosis may worsen.

Clinical Pain Advisor: What are remaining needs in this area in terms of research, physician education, or otherwise?

Dr Tariq: Although the National Institutes of Health (NIH) has allocated some funds and grants for research on headache and facial pain, these funds are insufficient, considering the scope of the problem. For example, expenditures related to migraine total billions of dollars in the United States alone. This gap is recognized by industry, which provides research funding (about 90% of research in this area is industry funded). Ideally, however, we would like to have NIH-funded studies to reduce the risk for bias.

Additionally, we need funding for more fellowships focusing on headache specialization, and we need a greater focus on headache in neurology residencies. It is currently not a mandatory elective, but I think we should require at least 4 weeks in a headache center.

References

1. National Institute of Neurological Disorders and Stroke. Headache: Hope Through Research. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Headache-Hope-Through-Research. Updated July 6, 2018. Accessed April 25, 2019.

2. Ahmed F. Headache disorders: differentiating and managing the common subtypes. Br J Pain. 2012;6(3):124-132.

3. Vgontzas A, Rizzoli PB. Nonmigraine headache and facial pain. Med Clin North Am. 2019;103(2):235-250.

4. Alvis-Miranda HR, Milena Castellar-Leones S, Alcala-Cerra G, Moscote-Salazar LR. Cerebral sinus venous thrombosis. J Neurosci Rural Pract. 2013;4(4):427-438.

5. Sattar A, Manousakis G, Jensen MB. Systematic review of reversible cerebral vasoconstriction syndrome. Expert Rev Cardiovasc Ther. 2010;8(10):1417-1421.

6. Hoffman JM, Lucas S, Dikmen S, et al. Natural history of headache after traumatic brain injury. J Neurotrauma. 2011;28(9):1719-1725.

This article originally appeared on Clinical Pain Advisor