Thunderclap Headache

Etiology

In a systematic review of causes of a sudden and severe headache (thunderclap headache), the authors, Devenney, Neale, and Forbes, conclude, “There are over 100 different published causes of sudden and severe headache, other than aneurysmal subarachnoid hemorrhage.”[6]

The 2 most common causes of secondary TCH are subarachnoid hemorrhage and reversible cerebral vasoconstriction syndrome (RCVS).[5]

Other causes include the following:

• Intracerebral hemorrhage, subdural hematoma, cervical artery dissection
• Ischemic stroke, cerebral venous sinus thrombosis (CVT)
• Spontaneous intracranial hypotension (SIH), acute hypertensive crisis
• Intracranial infection, complicated sinusitis
• Intracranial tumor, third ventricle colloid cyst, pituitary apoplexy
• Posterior reversible encephalopathy syndrome (PRES)

Epidemiology

A systematic literature review reported poor population-based data to accurately identify the true incidence and prevalence of thunderclap headaches.[6] The authors determined that the only estimate of a population-based incidence is from the study of a subset of a Swedish population. The incidence is reportedly 43 per 100,000 inhabitants older than 18 years annually.[7]

A population-based study in Italy showed a 0.3% lifetime prevalence of TCH in men and women aged 55 to 94.[8]

TCH in the pediatric population is considered very rare, but data are limited. In a recent retrospective study of children and adolescents aged 6 to 18 years presenting to a pediatric emergency department, TCH was diagnosed in 19 out of 2290 (0.8%) of the included patients.[9]

In patients presenting with a TCH, subarachnoid hemorrhage is found in 11 to 25% and other intracranial hemorrhages in 5 and 10%.[5][10]

TCH is the presenting symptom in 20% of patients with cervical artery dissection, 2 to 16% with cerebral venous thrombosis, 15% with intracranial hypotension, and 2% with bacterial or viral meningitis.[10]

Reversible cerebral vasoconstriction syndrome (RCVS) is a group of disorders characterized by severe headaches and cerebral vasoconstriction. The most common symptom of RCVS is a sudden, intense, thunderclap headache. RCVS represents a multitude of pathologies, so the true incidence of thunderclap is unknown.

Pathophysiology

Once the etiology of secondary TCH in a patient is known, the pathophysiology of the specific condition applies. However, generally speaking, the pathophysiology of primary and secondary TCH is unclear. Evidence suggests the sympathetic nervous system plays a central role in the abnormal cerebrovascular tone causing vasoconstriction and vasospasm, leading to head pain.[11]

History and Physical

TCH is often associated with a potentially fatal etiology, such as subarachnoid hemorrhage (SAH), and is considered a medical emergency. Therefore, a rapid, focused history and physical examination are essential for evaluating a patient presenting with TCH. Patients may describe their pain as “the worst headache ever” or “worst headache of my life.”

A focused history and neurologic examination will help differentiate TCH from other headache types, narrow the secondary TCH differential diagnoses, and guide the initial testing phase. What differentiates thunderclap headaches from other types of headaches is how rapidly they reach their peak intensity, not the headache intensity itself.[5] Primary and secondary TCH diagnostic criteria are (1) severe head pain with abrupt onset, (2) pain reaching maximum intensity in less than one minute, (3) pain lasting at least 5 minutes, and (4) headache not better accounted for by another ICHD-3 diagnosis.[4]

Remember that the 2 most common causes of TCH are SAH and RCVS, which can be difficult to distinguish by history and physical alone when the patient presents with an isolated TCH. Asking the patient about common RCVS precipitants may be helpful. RSVS precipitants include vasoactive substances such as cannabis, cocaine, amphetamines, triptans, noradrenergic and selective serotonergic antidepressants, and nasal decongestants; eclampsia and postpartum; binge alcohol consumption; surgical manipulation causing direct vessel injury; and strenuous physical exertion, sexual activity, and Valsalva maneuvers.[10][12][13] 

Multiple (2-10) excruciating, short-lived thunderclap headaches over a few days to weeks are highly suggestive of RCVS.[5][12]

SAH usually occurs during routine activity, including rest or sleep, but can occur during physical activity. Accompanying symptoms may include neck pain or stiffness, photophobia, vomiting, altered mental status, and loss of consciousness. Some patients report a sentinel headache, occurring days or weeks before presentation.[14] Potential focal exam findings include the following unilateral vision loss, visuospatial neglect, and ophthalmoplegia; retinal, subhyaloid, and vitreous hemorrhage; third and sixth nerve palsy; and hemiparesis, aphasia, and abulia.[15] 

The neurological examination can be categorized using the Hunt Hess scale or the World Federation of Neurological Surgeons scale.[14]

The following are signs and symptoms associated with other secondary TCH causes:

• Intracerebral hemorrhage - seizure, focal neurological deficits, altered level of consciousness
• Cervical artery dissection - neck pain, Horner syndrome, altered level of consciousness
• Cerebral venous thrombosis (CVT) - seizure, focal neurological deficits, the patient avoids lying flat
• Spontaneous intracranial hypotension (SIH) - patient avoids sitting up or standing up
• Meningitis - fever and neck stiffness
• Complicated sinusitis - fever, sinus pressure, the patient avoids lying flat
• Third ventricle colloid cyst - confusion, seizure, loss of consciousness
• Pituitary apoplexy - confusion, vision loss, diplopia, ophthalmoplegia, nausea, vomiting
• Posterior reversible encephalopathy syndrome (PRES) - seizure, focal neurological deficits, hypertension

Evaluation

The absence of associated symptoms and a normal physical examination do not exclude a serious etiology of secondary TCH.[10][16] The clinician must be cognizant of the numerous conditions that can present as secondary TCH because many are associated with significant morbidity and mortality.

Although diagnostic algorithms vary slightly, emergent noncontrast head computed tomography (CT) is the recommended first step after the history and physical, primarily to assess for SAH.[1][5][10][16][17][16] In addition to evaluating for SAH, noncontrast head CT may demonstrate findings associated with other intracranial causes of secondary TCH. Authors of a recent clinical review propose a diagnostic algorithm that includes adding head and neck CT angiography (CTA) to the initial imaging studies if there is a concern for cervical artery dissection or RCVS.[16]

Noncontrast head CT should be performed as soon as possible. Within the first 6 to 12 hours after headache onset, noncontrast head CT has a sensitivity of up to 100% for detecting SAH but decreases to 85-95% on day 2, 75% on day 3, and 50 to 60% after 5 days.[1][5] Because patients presenting with a TCH may have a mass lesion, brain imaging is required before performing a lumbar puncture (LP).

Diagnosis of SAH relies on noncontrast head CT, followed by LP if the CT findings are negative and the clinical suspicion is high. In a recent study, the diagnosis of SAH was 95% sensitive and 100% specific when the Ottawa SAH rule was used when interpreting a CT scan performed within 6 hours of headache onset.[18] CTA may be considered when evaluating SAH; however, if inconclusive, digital subtraction catheter angiography (DSA) with 3-dimensional reconstruction is the gold standard study for detecting aneurysms.[19][20]

When LP is indicated, it should be performed as soon as possible after the noncontrast head CT. However, the sensitivity of the cerebrospinal fluid (CSF) analysis for detecting SAH is higher if the LP is performed at least 6 hours after symptom onset.[21] LP should include measuring the opening pressure because a high pressure may point to CVT and a low pressure to SIH.[10][16] CSF analysis should include white and red blood cell counts, protein and glucose concentrations, and visual inspection for xanthochromia.[1][5][10][16][17] When available, spectrophotometry is recommended because visual inspection for xanthochromia is associated with a high rate of false negatives. Spectrophotometry also helps to decrease false-positive interpretations.[1] Spectrophotometry has a high sensitivity for detecting SAH when the CSF is obtained between 12 hours and 2 weeks following the SAH.[5][17] Other CSF studies following LP, such as testing for central nervous system infections, may also be indicated.

Suppose the noncontrast head CT and CSF analyses are nondiagnostic. In that case, further imaging studies may include contrast-enhanced brain magnetic resonance (MR) imaging, head and neck CTA, and head and neck MR angiography.[5][10] Digital subtraction angiography (DSA) may be used for definitive imaging when RCVS is strongly suspected, or the patient’s clinical condition worsens, and noninvasive methods have been unremarkable.[13]

Treatment / Management

There are only a few case reports on primary TCH treatment, and evidence supporting that TCH exists as a primary disorder is poor. Therefore, the treatment and management are focused almost exclusively on secondary TCH.[1][4] Once the diagnosis has been established, secondary TCH management should be tailored to the underlying cause.

Differential Diagnosis

According to the ICHD-3, “Vasoconstrictions may not be observed in the early stage of RCVS. For this reason, probable primary thunderclap headache is not a diagnosis that should be made even temporarily.”[4]

The differential diagnosis includes other primary headache disorders and secondary TCH causes. Primary cough headache, primary exercise headache, and primary headache associated with sexual activity can all present as TCH.[4] The 2 most common causes of secondary TCH are SAH and RCVS.[5] Other causes include the following intracerebral hemorrhage, subdural hematoma, cervical artery dissection, ischemic stroke, CVT, SIH, acute hypertensive crisis, intracranial infection, complicated sinusitis, intracranial tumor, third ventricle colloid cyst, pituitary apoplexy, and PRES.[4][5][10][17][22][23]

Prognosis

The differential diagnosis of secondary TCH is extensive; therefore, this section is limited to the 2 most common causes, SAH and RCVS, and comments on the pediatric population.

Approximately 10 to 18% of patients with SAH die before arriving at a hospital. Mortality at one year is 35 to 65%, and 25 to 33% of survivors will suffer reduced activities of daily living, decreased quality of life, and neurological disability.[14][24][25][26]

Importantly, "reversible" in the acronym RCVS refers to reversible vasoconstriction, not necessarily signs and symptoms associated with the syndrome. For example, over half of the patients report headaches years after diagnosis.[27] Most patients with RCVS have a self-limited course lasting days to weeks, with vasoconstriction usually resolving within 3 months. Overall, the long-term clinical outcomes associated with RCVS are excellent in over 90% of patients.[28][29]

In a recent United States population study, patient factors independently associated with a poor outcome or death in patients with RCVS were advanced age, female sex, intracerebral hemorrhage, ischemic stroke, seizure disorder, reversible brain edema, atrial fibrillation, and chronic kidney disease.[30] Glucocorticoid exposure may also contribute to worsening RCVS outcomes.[28]

As mentioned previously, TCH in the pediatric population is very rare. In a 3-year retrospective study of children and adolescents aged 6 to 18 years, all patients diagnosed with TCH had a benign course.[9]

Complications

The complications associated with secondary TCH depend on the attributable cause. Secondary brain injury can occur in SAH due to intracerebral hemorrhage, intraventricular hemorrhage, intracranial pressure, hydrocephalus, subdural hematoma, or delayed cerebral ischemia. Medical complications are common and significantly impact outcomes. Reported complications include pyrexia, sepsis, aspiration pneumonia, cardiac dysfunction, anemia, hyponatremia, hyperglycemia, and deep venous thrombosis.[14][31]

Although one- to two-thirds of patients with RCVS develop ischemic or hemorrhagic brain lesions (or both), most achieve functional recovery and independence. Overall, the long-term recurrence rate of RCVS is low, and the relapse is typically benign.[27][28] However, anxiety or depression may be associated with decreased quality of life.[27]