Clinical manifestations

Presentation and course

The ICHD-3 diagnostic criteria for primary exercise headache are detailed in Table 1.

A variety of sports have been associated with primary exercise headache, including running (22), weightlifting (35), Australian Football League (31), rugby union (49), cycling (46), and swimming (21; 32). It could be noted that two of the three swimming cases reported by Indo and Takahashi may have been cold-stimulus headaches, and two had migrainous features.

Most patients report onset of headache within 30 minutes of cessation of exercise (36; 45). The headache duration can range from minutes to less than 1 day (16; 36; 45). Adolescents may report a shorter headache duration, with most respondents reporting attacks up to 4 hours (04). A more prolonged form of exercise-induced headache has been reported. Attacks can last more than a day, with the longest reported attacks lasting up to 2 days (36).

Most patients report a pulsating headache; however, the nature of the pain can be described as aching, pounding, or throbbing (04; 45). The headache can be either bilateral or unilateral. More recent studies report a higher incidence of bilateral headache (46; 16; 36; 45). The frontal region is the most frequently reported headache location (04; 36; 45). Pain intensity is variable.

Patients who experience primary exercise headache may also report many of the characteristics of migraine, such as nausea, vomiting, photophobia, and phonophobia (04; 46). These symptoms were reported more often in females (04). Patients with comorbid migraine and primary exercise headache are more likely to report headaches lasting more than 1 hour, nausea, photophobia, and phonophobia than patients with primary exercise headache alone (04). However, this finding should be interpreted with caution as it would be difficult to differentiate primary exercise headache with migraine features from migraine triggered by physical activity (19). A principle used in headache classification is that the diagnosis should not be if the phenotype can be accounted for by another headache diagnosis. It could be argued for research purposes that only featureless exercise-triggered headache should be classified as such. Indeed, in clinical practice there is little to be gained in the diagnosis of exercise headache in the presence of migrainous features as treatments for migraine increase over time.

Heat, high humidity, changing barometric pressure, exercise at high altitudes, caffeine, poor nutrition, hypoglycemia, and alcohol usage are believed to be contributing factors (36; 45).

Table 1. Diagnostic Criteria for Primary Exercise Headache

Prognosis and complications

The prognosis for patients with primary exercise headache is good. Spontaneous resolution has been reported by patients after months to several years (38; 40; 41; 16). In the cohort reported by Rooke, approximately one third of patients with primary exercise headache will experience spontaneous resolution within 5 years of onset, and approximately 80% will have spontaneous remission after 10 years of onset (38). The most recent cohort described by Hanashiro and colleagues found almost all patients had resolution within their 1-year follow-up from diagnosis.

Clinical vignette

A 62-year-old female presented with a 4-year history of headache on 28 out of 30 days a month. The headaches were always associated with strenuous exercise and would occur within 15 minutes of exercise cessation.

The pain was in the left facial temporal regions with pain involvement bilaterally in the throat, neck, shoulder, and upper and lower teeth. The pain typically lasts for 20 minutes with a range of 2 to 60 minutes, where resolution occurs with cessation of exercise. The headache was not associated with aura symptoms, migrainous features, or cranial autonomic symptoms. She did not report premonitory-like or postdromal symptoms.

Paracetamol was not effective in treating the headache.

The headache was not associated with cough or sexual activity.

As a teen, she had headaches, which would be consistent with migraine with visual aura. There was a family history of migraine in her mother.

The neurologic examination was unremarkable. The brain MRI, neck MRI, intracranial and extracranial MRA were normal. She was assessed by cardiology, and she did not have significant coronary artery disease.

Biological basis

Etiology and pathogenesis

Numerous theories have been proposed to explain headache associated with exertion, but objective data are lacking in most cases, and the pathophysiology of primary exercise headache remains unclear (15).

Powell proposed strain or stretch of the cervical ligaments and tendons with the development of excessive muscle contraction as an explanation for individuals who complain of headache associated with weightlifting (35).

A hexamethylpropyleneamine oxime SPECT of a 15-year-old with exercise-induced headache revealed transient hypoperfusion in the frontal lobes bilaterally during the headache (03), suggesting changes in cerebral hemodynamics.

Heckmann and colleagues observed abnormal cerebrovascular autoregulation via stress transcranial Doppler in one patient with exercise-induced headache (20). They observed a marked elevation in blood flow velocity with minimal changes in calculated resistance, which they suggested indicates an abnormal vascular myogenic response.

Cerebral arterial vasospasm has been observed in one patient with both primary headache associated with sexual activity and primary exercise headache (39).

Primary exercise headache has been proposed to be a venous disorder (10). The prevalence of jugular valve incompetence leading to a transient increase of intracranial pressure during exertion has been shown to be much higher (70%) in patients with primary exercise headache when compared with controls (20%), suggesting that intracranial venous congestion caused by retrograde jugular venous flow may play a role (09). The prevalence of cerebral venous stenosis has been shown to be increased in patients with exercise-induced headaches in a study that included patients with cough, exercise, and sexual headaches, as compared to controls (11).

Calcitonin gene-related peptide (CGRP) has been established as an important neurotransmitter in the pathogenesis of migraine (12). Calcitonin gene-related peptide has been demonstrated to increase with exercise (25). Although calcitonin gene-related peptide has been hypothesized to play a role in primary exercise headache, the one study that explored this found no difference in calcitonin gene-related peptide rise between runners without a background of headache, migraine sufferers, and runners with primary exercise headache (43).

Epidemiology

Rasmussen and Olesen have assessed the lifetime prevalence of headache disorders in a cross-sectional epidemiologic survey of a representative 25- to 64-year-old general population (37). They found a lifetime prevalence of 1% for “benign exertional headache”. In an epidemiological survey in Norway involving 1838 participants, 12.3% referred to exercise headache (40; 41); in a survey of 1963 adolescents between the ages of 13 and 15 in Taiwan, the prevalence of exercise headache was as high as 30.4% (04). A cluster-sampled cross-sectional study of the population of Tehran in 2079 individuals reported a prevalence of 7.3% (36), and a study of 300 male conscripts between the ages of 18 to 26 reported a prevalence of 12.7% (45).

Earlier prevalence studies suggest that primary exercise headache appears to be more frequent in men (42; 38; 34). However, later studies demonstrate contrary evidence (04; 16; 36).

Two studies have shown a high rate of comorbidity with migraine (04; 16).

A survey of 4000 competitive cyclists revealed a prevalence of 26% (46), suggesting its burden in athletes may be underestimated.

Prevention

When exercise headache is diagnosed, patients can limit their exercise. Improved overall physical conditioning and a warm-up period before exercise may help prevent exercise-induced headaches (24).

Differential diagnosis

Associated or underlying disorders

A comorbid diagnosis of migraine is found in one third to two thirds of patients with primary exercise headache (04; 16).

Approximately one third and 17% of patients with primary exercise headache also have a diagnosis of primary headache associated with sexual activity and primary cough headache, respectively. This observation may be due to shared pathophysiology. Cerebral venous stenosis was observed in patients with either primary cough, primary exercise, or primary headache associated with sexual activity (11). However, the pathogeneses of these disorders remain unclear.

An adequate history will usually reveal the diagnosis of primary exercise headache, but patients with mass lesions, structural malformations, and vascular malformations can also have headaches with exertion. About one third of cases of headaches precipitated by exercise are secondary to an underlying pathology (34). Pheochromocytoma, arterial dissection, hypoplasia of the aortic arch after successful coarctation repair, elongated styloid process, and fusiform aneurysms of the vertebral artery, although rare, have been reported as responsible for exercise-induced headache (05; 27; 30). Rarely, exercise headache is a symptom of middle cerebral artery dissection (01). The diagnosis of primary exercise headache can be made only after a thorough examination to rule out intracranial disease or structural malformation.

Cardiac cephalalgia. Rarely, patients with arteriosclerotic coronary artery disease may have exercise-induced headaches that begin with exertion and are relieved by rest. This syndrome was first described in 1997 (26), and 35 cases of cardiac cephalalgia have been reported; these were reviewed in 2017 (47).

Patients who present with this headache often report symptoms of cardiac ischemia, such as chest pain and dyspnea; however, an absence of these symptoms does not exclude the diagnosis.

This headache is most often a severe bilateral occipital headache with associated nausea in a third of cases (47). Photophobia and phonophobia would be unexpected associated features and each of the symptoms has been reported once in the 35 case reports of cardiac cephalalgia (47).

Cardiac cephalalgia occurring at rest has been described (14; 13).

The International Headache Society defines cardiac cephalalgia as headache usually, but not always, aggravated by exercise, occurring during an episode of myocardial ischemia and relieved by nitroglycerin (19).

The International Headache Society defines cardiac cephalalgia as headache usually, but not always, aggravated by exercise, occurring during an episode of myocardial ischemia and relieved by nitroglycerine (19).

Treadmill testing can reveal S-T segment electrocardiographic changes appearing with the headache.

Management of the underlying coronary disease with percutaneous intervention or coronary bypass surgery results in the resolution of headaches (48).

Failure to recognize and correctly diagnose cardiac cephalalgia can have serious consequences. Distinguishing this disorder from migraine without aura is crucial, particularly because vasoconstrictor medications (eg, triptans or ergots) are indicated for the treatment of an acute migraine attack but contraindicated for patients with cardiovascular disease (08).

Table 2. Diagnostic Criteria for Cardiac Cephalalgia

Diagnostic workup

Because both benign and malignant forms of headache are associated with exercise.

About one third of cases of headache precipitated by exercise are secondary to an underlying pathology and include primary brain tumor, metastatic disease, subarachnoid hemorrhage, and unruptured aneurysms (34).

Therefore, an MRI examination is usually required to evaluate patients with exercise headache. If an aneurysm is suspected, or if there is doubt, further neurologic studies are indicated, particularly lumbar puncture, CT scan of the head, MRA, or CT angiogram.

Management

Moderation of exercise or activity may be all that is required. A warmup period before strenuous exercise has been recommended (24).

Prophylactic use of indomethacin in doses varying from 25 to 150 mg a day has been recommended for more prolonged exercise headaches (07; 29). Daily indomethacin in varying doses between 25 to 150 mg has been reported to completely control exercise-induced headaches (06). The history-taking should include exercise frequency prior to introducing indomethacin. In patients who exercise frequently, regular administration of a proton pump inhibitor should be considered to prevent gastric side effects of indomethacin.

Only rarely have migraine preventive drugs such as propranolol or flunarizine been indicated in the treatment of exercise-induced headaches (34; 33).

Other approaches that may be recommended based on the authors’ experience are the use of a longer-acting NSAID, such as naproxen, or more recently, rimegepant 75 mg. Utilization of treatments targeting the CGRP pathway in Valsalva-induced headache syndromes, including primary exercise headache, remains a budding frontier with success with a CGRP monoclonal antibody in primary headache associated with sexual activity (28).

Outcomes

Over 80% of patients will respond to indomethacin, with the response within 1 to 4 weeks of initiation (06).

The maximum required treatment period with propranolol has been reported to be 6 months (33).

Special considerations

Pregnancy

The onset of an exertion-related headache in pregnancy is a red flag and should prompt a detailed evaluation with history, examination, and investigation for a secondary cause.

Anesthesia

This diagnosis does not preclude anesthesia as indicated or necessary. No additional precautions need to be undertaken for anesthesia in patients with a diagnosis of primary exercise headache.