‘It’s the Worst Headache of My Life:’ Subarachnoid Hemorrhage — A Brief Review
By Saadia R. Akhtar, MD, MSc, St. Luke’s Idaho Pulmonary Associates, Boise. Dr. Akhtar reports no financial relationships relevant to this field of study.
Introduction and Epidemiology
Subarachnoid hemorrhage (SAH) is a stroke syndrome, defined as “rapidly developing neurological dysfunction and/or headache because of bleeding into the subarachnoid space (the space between the subarachnoid membrane and the pia mater of the brain or spinal cord), which is not caused by trauma.”1 It is a dire condition with high morbidity and mortality.
SAH accounts for about 5-10% of all strokes, affecting 8-10 per 100,000 population or about 30,000 persons in the United States yearly. Patients with SAH are usually between ages 40 and 60 years (mean 55 years); women and African Americans are at increased risk. Sixteen percent of these patients die at the time of the initial bleed. The overall mortality rate is high at 30-45%; two-thirds of survivors are left with significant permanent neurological impairment.2,3
SAH occurs most commonly (85% of the time) as a result of rupture of a congenital central nervous system (CNS) aneurysm. This article will focus on that. Other causes include arteriovenous malformations, vasculitis, amyloid angiopathy, etc. The rate of incidentally noted CNS aneurysm (from radiographic or autopsy studies) is high at 5% in the United States (closer to 10% in patients with a strong family history of CNS aneurysms) but, as noted above, only a small number of these will rupture. About 30% of affected patients have multiple CNS aneurysms. The overall estimated risk of rupture is ≤ 1% yearly, with considerably increased risk for aneurysms > 10 mm. The majority of CNS aneurysms are of the saccular (or berry) type and involve the large arteries rising from the Circle of Willis, particularly the anterior and posterior communicating arteries.2,4,5
Certain genetic conditions and connective tissue disorders, such as polycystic kidney disease and Ehler-Danlos syndrome, are associated with an increased likelihood of CNS aneurysm formation and SAH. Even in the absence of known genetic conditions, a family history of SAH increases an individual’s risk. Other significant risk factors for SAH include hypertension, alcohol, or cocaine abuse.4,6 Current cigarette smoking is the most significant and well-documented modifiable risk factor. It has a dose-dependent effect that disappears within a few years of smoking cessation.
CNS aneurysms are generally asymptomatic until rupture occurs. The acute symptoms of SAH are primarily a reflection of increased intracranial pressure due to the release and spread of blood in the subarachnoid space and cerebrospinal fluid (CSF).
More than 80% of patients will present with headache and it is important to maintain a high index of suspicion for possible SAH. (SAH accounts for only about 1% of headaches presenting to the emergency department; the diagnosis may be missed initially in 5-25% of patients.) The classic history is that of abrupt onset of severe headache, typically “the worst headache of my life” with “thunderclap” quality; that is, reaching its most severe and intense pain within seconds to a few minutes of onset. This latter feature is most specific for SAH. The headache may come on during exertion or rest or may even awaken the patient from sleep. In up to 40% of patients, this “worst headache” may be preceded by a sentinel headache (a smaller leak from the aneurysm) 2-8 weeks prior. About one-third of patients present with headache as the only complaint, but in others, associated symptoms occur including nausea, vomiting, photophobia, neck pain or stiffness, seizure, or altered level of consciousness. It is uncommon to find focal neurological deficits on initial presentation.7,8
Hypertension and tachycardia are often present. Electrocardiographic abnormalities (thought to be of neurogenic etiology) are common, including QTc prolongation or ST and T changes mimicking primary cardiac ischemia. Malignant ventricular arrhythmias may occur; sudden cardiac arrest is the presenting finding in up to 3% of cases of SAH.9
The initial diagnostic study of choice is a noncontrast head CT; the sensitivity of this for SAH is close to 100% for the first few hours to 3 days after the bleed. Accuracy of noncontrast head CT for SAH declines over time because of the normal circulation of the CSF and breakdown of blood. If the head CT is negative and clinical suspicion for recent SAH is high, lumbar puncture should be performed next to look for xanthochromia, which is the yellowish discoloration of CSF due to the presence of bilirubin. It may take 6-12 hours after the initial bleed for degradation of blood and development of xanthochromia.
Once SAH is confirmed, it is essential to image the intracranial vessels as quickly as possible to look for and treat the underlying source of the bleed before rebleeding occurs. Head CT angiogram (CTA) will usually identify the source (the aneurysm), but small aneurysms (< 3 mm) may be missed. For patients with SAH and negative CTA, digital subtraction cerebral angiography must be considered.8,10,11
Multimodal (including MRA) brain MRI has similar sensitivity to CT/CTA and may eliminate the need for contrast medium. However, acquisition of images takes longer, availability/experience may be limited, and cost is generally greater than for CT; thus this is not recommended as the first-line diagnostic study for most patients.7
In 15-22% of patients, no clear cause of SAH is found on the initial studies, and repeat angiogram is recommended in 4-14 days.12
SAH is a clinical emergency due to its high morbidity and mortality, which are further worsened by any delays in definitive treatment of the underlying aneurysm. The priority is to quickly occlude the ruptured aneurysm to prevent rebleeding and then avoid vasospasm. Usual ICU supportive care and monitoring for other problems (seizures, hydrocephalus, elevated intracranial pressure [ICP]) is also essential.
All patients with SAH should be admitted to and monitored in an ICU with involvement of neurosurgical and critical care providers and hourly assessment of vital signs and neurological examination. Cautious blood pressure (BP) control is important to minimize risk of rebleeding, with goal SBP ≤ 160-180 mmHg, at least until definitive treatment of the aneurysm. Nicardipine is recommended as first-line therapy. Measures should be taken to avoid raising ICP: quiet bed rest, analgesics, antipyretics, (central fever occurs in about 20% of patients), antiemetics, etc.10,12 Careful monitoring of the airway and usual measures to avoid aspiration are essential. Provide deep venous thrombosis prophylaxis with pneumatic compression stockings. Once the aneurysm is obliterated, pharmacologic prophylaxis may be added. Usual glucose control is indicated. Seizure prophylaxis is not universally recommended, although some experts suggest considering it (usually with levetiracetam), but treatment should be initiated right away if seizure occurs. Finally, for patients on warfarin, anticoagulation should be reversed and antiplatelet agents should also be held.8
The risk of rebleeding in the first 72 hours after SAH is quite high, particularly within the first 6-24 hours. Occlusion of the ruptured aneurysm is the only effective preventive measure/treatment and should be performed as soon as possible in the 72-hour window. There are two possible approaches, endovascular coiling or neurosurgical clipping. In general, when an aneurysm is amenable to either approach, coiling is recommended. There has been one large, multicenter, randomized, clinical trial of > 2000 patients that provides support for this, demonstrating reduced death and disability (24% vs 31%) at 1 year in those treated with coiling.13 However, it may be more difficult to achieve complete obliteration of the aneurysm with coiling and recurrence of aneurysm and bleeding may occur; thus, delayed follow-up imaging is essential, with retreatment if there is evidence of persistence or recurrence of aneurysm.13 For certain clinical scenarios (such as advanced patient age, poor neurological status at presentation, wide-mouthed aneurysm, and middle cerebral artery aneurysm), surgical clipping is recommended as the first-line intervention.10,12
Symptomatic vasospasm occurs in up to 30% of patients after SAH, leading to cerebral ischemia and infarction, and this is the leading cause of morbidity and mortality in SAH. It is believed to be caused by imbalance in vasoactive mediators due to the impact of metabolites of blood cells in the CNS. Vasospasm typically begins on or after day 3, peaks at about day 7-10, and may take up to 3-4 weeks to fully resolve. Patients develop new focal neurological findings or altered level of consciousness (persistent decline in Glasgow coma score by at least 2). Transcranial Doppler ultrasound will confirm the diagnosis. Nimodipine (60 mg orally every 4 hours for 21 days) is currently the only proven effective therapy and is standard of care for prevention of vasospasm. It has been shown to significantly reduce the risk of secondary ischemia, poor neurological outcome, and death, although primary vasodilation may not be the mechanism of action.14 If symptomatic vasospasm occurs, supportive treatment with “triple H” therapy should be initiated: i.e., hypertension (induced, with vasopressors), hypervolemia (current practice suggests aiming for euvolemia), and hemodilution (mild to moderate, with maintenance fluids), with the goal of increasing mean arterial pressure and, thus, cerebral perfusion pressure. Endovascular treatment (intra-arterial infusion of vasodilators or balloon angioplasty) for symptomatic vasospasm is a newer approach that shows promise in some case series and clinical reports. It appears to be most effective when used early, within 1-2 hours of onset of symptoms, and produces good radiographic results (resolution of vasospasm on imaging). However, the duration of effect is variable, there are significant potential risks (vessel injury, rebleeding), and the extent and significance of short- and long-term clinical improvement are unknown thus far.10,12,15
Delayed cerebral ischemia can develop in patients with SAH, even in the absence of vasospasm. It remains unclear how to prevent or detect this early on and investigations are ongoing. At this time, there are no data to support routine intracerebral monitoring such as ICP monitoring with ventricular or lumbar drains, continuous electroencephalography, or jugular bulb oximetry.
Hydrocephalus is commonly seen radiographically, but patients may be asymptomatic and findings may resolve spontaneously in about half of affected patients within 24 hours. When persistent, treatment is generally with placement of an extra-ventricular drain (less commonly, a lumbar drain).10
There are ongoing investigations of medical therapies for SAH. For prevention of rebleeding, antifibrinolytics (such as tranexamic acid) continue to be discussed; older studies showed reduced risk of rebleeding, no impact on other outcomes, and increased risk of cerebral ischemia or systemic thromboemboli, but shorter-term use may have greater benefit without the adverse effects and thus has been advocated by newer reports.16 Recombinant factor VIIa has been tried for similar reasons but has been associated with systemic venous thromboemboli. For prevention of vasospasm, magnesium, statins, tirilazad, and endothelin-receptor antagonists have all been tried, thus far with equivocal or negative results.17,18
The best predictors of outcome are the patient’s neurological condition on presentation, age (inverse relationship), and the amount of extravasated blood seen on CT scan. There are several standardized scoring systems used to define SAH for documentation and clinical communication. The Hunt and Hess scale rates neurological status from grade 1 (asymptomatic or mild headache) to grade 5 (coma and posturing); the World Federation of Neurological Surgeons’ score incorporates the Glasgow Coma Scale score and the presence of motor deficits. Two other commonly used scoring systems, Fisher scale and Classen grading system, describe the extent of blood on head CT. Unfortunately, none of these scoring systems are well validated. They have not been prospectively compared to each other and have variable accuracy and utility for predicting outcomes.19
Accurate diagnosis and timely treatment of aneurysmal SAH require a high index of suspicion, rapid imaging (noncontrast head CT, possible lumbar puncture, and some sort of angiographic study), definitive occlusion of the aneurysm to prevent rebleeding, and aggressive supportive care to prevent or limit delayed cerebral ischemia. Even with the best care, aneurysmal SAH carries very high morbidity and mortality. Our understanding of SAH and how best to manage it remains in its infancy, and ongoing investigation is essential to improve future outcomes.
1. Sacco RL, et al. An Updated Definition of Stroke for the 21st Century: A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 2013; May 7. [Epub ahead of print.]
2. Rincon F, et al. The epidemiology of admissions of non-traumatic subarachnoid hemorrhage in the United States. Neurosurgery 2013; April [Epub ahead of print.]
3. The Brain Aneurysm Foundation. Understanding: Brain Aneurysm Statistics and Facts. http://www.bafound.org/node/124. Accessed June 6, 2013.
4. Feigin VL, et al. Risk factors for subarachnoid hemorrhage: An updated systematic review of epidemiological studies. Stroke 2005;36:2773-2780.
5. Unruptured intracranial aneurysms — risk of rupture and risks of surgical intervention. International Study of Unruptured Intracranial Aneurysms Investigators. N Engl J Med 1998;339:1725-1733.
6. Vega C, et al. Intracranial aneurysms: Current evidence and clinical practice. Am Fam Physician 2002;66:601-608.
7. Venti M. Subarachnoid and intraventricular hemorrhage. Front Neurol Neurosci 2012;30:149-153.
8. Edlow JA, et al. Emergency neurological life support: Subarachnoid hemorrhage. Neurocrit Care 2012;17(Suppl 1): S47-S53.
9. Sommargren CE. Electrocardiographic abnormalities in patients with subarachnoid hemorrhage. Am J Crit Care 2002;11:48-56.
10. Connolly ES Jr, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2012;43:1711-1737.
11. Nentwich LM, Veloz W. Neuroimaging in acute stroke. Emerg Med Clin N Am 2012;30:659-680.
12. Steiner T, et al. European stroke organization guidelines for the management of intracranial aneurysms and subarachnoid haemorrhage. Cerebrovasc Dis 2013;35:93-112.
13. Molyneux AJ, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: A randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 2005;366: 809-817.
14. Dorhout Mees SM, et al. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2007; (3):CD000277.
15. Rahme R, et al. Endovascular management of posthemorrhagic cerebral vasospasm: Indications, technical nuances, and results. Acta Neurochir Suppl 2013;115:107-112.
16. Chwajol M, et al. Antifibrinolytic therapy to prevent early rebleeding after subarachnoid hemorrhage. Neurocrit Care 2008; 8:418-426.
17. Vergouwen MD, et al. Effect of statin treatment on vasospasm, delayed cerebral ischemia, and functional outcome in patients with aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis update. Stroke 2010;41:e47-e52.
18. Vergouwen MD, et al. Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis update. Stroke 2012;43:2671-2676.
19. Rosen DS, Macdonald RL. Subarachnoid hemorrhage grading scales: A systematic review. Neurocrit Care 2005;2:110-118.