Summary:
Aneurysmal subarachnoid hemorrhage (SAH) is a serious cause of stroke that affects 30,000 patients in North America annually. Due to a wide spectrum of presentations, misdiagnosis of SAH has been reported to occur in a significant proportion of cases. Headache, the most common chief complaint, may be an isolated finding; the neurological examination may be normal and neck stiffness absent. Emergency physicians must decide which patients to evaluate beyond history and physical examination. This evaluation–computed tomography (CT) scanning and lumbar puncture (LP)–is straightforward, but each test has important limitations. CT sensitivity falls with time from onset of symptoms and is lower in mildly affected patients. Traumatic LP must be distinguished from true SAH. Cerebrospinal fluid analysis centers on measuring xanthochromia. Debate exists about the best method to measure it–visual inspection or spectrophotometry. An LP-first strategy is also discussed. If SAH is diagnosed, the priority shifts to specialist consultation and cerebrovascular imaging to define the offending vascular lesion. The sensitivity of CT and magnetic resonance angiography are approaching that of conventional catheter angiography. Emergency physicians must also address various management issues to treat or prevent early complications. Endovascular therapy is being increasingly used, and disposition to neurovascular centers that offer the full range of treatments leads to better patient outcomes. Emergency physicians must be expert in the diagnosis and initial stabilization of patients with SAH. Treatment in a hospital with both neurosurgical and endovascular capability is becoming the norm.
Introduction
Headaches, an exceedingly common complaint, are mostly caused by migraine, tension-type, and other primary headache disorders. Two percent of all Emergency Department (ED) patients have a chief complaint of headache, and of those, 2% have a serious life-, limb-, brain-, or vision-threatening condition diagnosed in the ED ( Table 1 ).[1] One such disorder is subarachnoid hemorrhage (SAH). Although trauma is the leading cause of SAH, ruptured intracranial aneurysms account for 80% of non-traumatic cases.[2,3] Of the remaining 20%, half are caused by non-aneurysmal venous "perimesencephalic" hemorrhages. The other 10% are caused by arteriovenous malformations, other vascular lesions, tumors, and other less common disorders.[2-5]
One in 100 headache patients presenting to EDs have SAH.[6-8] Of patients with severe, abrupt-onset headache and normal neurological examinations, about 10% have SAH.[9-12] The initial bleed may be fatal, may result in significant neurological dysfunction, or may produce relatively minor symptoms. Because early treatment is associated with improved outcomes, timely diagnosis is critical.[13] Despite a straightforward diagnostic algorithm, misdiagnosis remains common. Mildly affected patients who are most commonly misdiagnosed also have the best outcomes if correctly identified and treated.[2] Misdiagnosis of SAH is an important cause of medico-legal actions against physicians.[14,15]
This review updates emergency physicians on diagnostic and management issues of SAH that have emerged over the last several years.
Incidence of Aneurysms and Effects of Rupture
Intracranial aneurysms are common and are located on the large arteries of the circle of Willis and its branches. Autopsy series uncover them in 0.4–3.6% of individuals, whereas cerebral angiography documents incidental aneurysms in 3.7–6.0% of patients. Therefore, roughly 2% of all individuals harbor aneurysms.[16] Approximately 80–85% of these lesions are in the anterior cerebral circulation, and the rest are in the posterior circulation (Figure 1); cerebral aneurysms are multiple in 25% of cases.[17]
|
|
Figure 1. Cerebrovascular anatomy–Circle of Willis (shaded volume rendering images of 3-D rotational angiograms). The cerebrovascular circulation is conventionally divided into the (A) anterior circulation (internal carotid artery and its branches) and the (B) posterior circulation (the vertebral arteries and its branches). The two systems are linked up by the posterior communicating arteries, which connect the internal carotid artery and the posterior cerebral artery. The 3rd cranial nerve sits adjacent to the posterior communicating artery, which is the reason that aneurysms in this location are often associated with 3rd cranial nerve palsy. The red dots on the figure represent areas where aneurysms commonly form, typically at arterial bifurcations. ICA = internal carotid artery, PComm = posterior communicating artery, MCA = middle cerebral artery; AComm = anterior communicating artery, ACA = anterior cerebral artery; VA = vertebral artery, PICA and AICA = posterior (and anterior) inferior cerebellar artery, SCS = superior cerebellar artery; PCA = posterior cerebral artery. |
When an aneurysm does rupture, the intracranial pressure (ICP) rises precipitously. Cerebral perfusion may transiently cease, resulting in unconsciousness, or death, if the ICP is sufficiently high to cause irreversible structural damage or halt cerebral perfusion. The mortality rates on the first day and during the first month after hemorrhage are approximately 12% and 40%, respectively.[22-27] The patient's clinical status at diagnosis is commonly measured by two clinical metrics–the Hunt and Hess (H&H) grade and the World Federation of Neurosurgical Societies (WFNS) scale ( Table 2 ). Hunt and Hess' original article correlated clinical grade with mortality.[28] Although commonly used, the H&H scale is somewhat subjective, and is associated with significant inter-observer variability.[29] The more objective WFNS scale is based on the Glasgow Coma Scale (GCS) and presence or absence of motor deficits.[30] Other grading scales also have been proposed but are not widely used.[31,32] Their common thread is that higher scores indicate worse clinical condition and result in worse outcomes.
SAH results in hemodynamic instability, metabolic disturbances, and neurocardiogenic injury including ventricular dysfunction, cardiac enzyme leak, and electrocardiographic abnormalities.[33-38]
Epidemiology
The incidence of SAH has not diminished over time and is roughly 10 per 100,000 of the population and more common in Blacks and Hispanics than Whites.[13,39,40,41] Women, especially post-menopause, are more frequently affected than men.[13,23,27,42] Some studies suggest a rising incidence in elderly patients, and a decreasing incidence in men.[27,43]
Given that the prevalence of aneurysms is approximately 200 times higher than the annual incidence of SAH, it is clear that most aneurysms do not rupture. Peak age at rupture is 50 years.[17] Important risks for SAH include heavy alcohol use, cigarette smoking, hypertension, and possibly oral contraception use.[13,44-48] A positive family or past personal history of SAH also increases risk.[45,49,50] Cocaine use may also increase the risk in those patients who have aneurysms.[51] Other disorders associated with SAH include autosomal dominant polycystic kidney disease, Ehlers-Danlos syndrome type IV, and neurofibromatosis type 1.[52]
Diagnosis
Which Patients to Evaluate?
Numerous studies over several decades document that misdiagnosis of SAH occurs approximately 25% of the time (12–50%), even in the era of ready access to cranial computed tomography (CT) scanning.[53-60] These studies show three recurring, preventable reasons for misdiagnosis–failure to consider the diagnosis, failure to perform (and correctly interpret) CT scans, and failure to perform (and correctly interpret the results of) lumbar puncture (LP).[2,3] One large study found that failure to obtain a CT scan was the most common error.[55] The largest and most recent report, a Canadian population-based study, found a much lower rate of ED-attributable SAH misdiagnosis (5.4%), and older studies include misdiagnosis attributable to patients, primary care physicians, and specialists.[61] Over time, the misdiagnosis rate may be decreasing, but methodological differences across these studies preclude a firm conclusion.[62]
The first decision emergency physicians must make when evaluating patients with headache is whether or not to pursue any diagnostic studies beyond history and physical examination. The classic history of SAH–abrupt onset of worst headache of life ("thunderclap" headache) during exercise or Valsalva, associated with transient syncope with vomiting–presents little diagnostic difficulty.[63] Evaluation of headache patients with cognitive impairment, new focal abnormalities, or meningismus, is also clear cut.
Less clear is when to evaluate patients with milder symptoms and normal neurological examinations. To date, no prospective published studies help physicians know which elements of the history predict SAH in this group.
Until such data are available, we believe that four elements of the history best help identify the majority of these patients: onset, severity, quality, and associated symptoms.[3,64] The onset is usually sudden and the severity is generally "worst of life." Because headaches are so common, comparing the quality of the index headache with any prior ones is important. Patients usually describe the headache from SAH as clearly different from prior headaches. Ten percent of neurologically normal patients with abrupt-onset, severe, and unusual headaches will have SAH.[9-12] Half of all SAH patients present with atypical or mild features.[17,28,65] Associated symptoms, such as nausea, vomiting, neck pain, and stiffness are common. However, neck stiffness (meningismus) may be absent, especially in the early hours.[5,64] Headache patients over age 50 years are more likely to have SAH and other serious intracranial pathology.[1,8] There are many diagnostic pitfalls to be avoided ( Table 3 ).[2,3,64]
Many SAH patients have headaches that begin at rest or during quiet activities.[66,67] Others present with symptoms such as vomiting, fever and headache, mild confusion, delirium, or severe neck pain that suggest other diagnoses such as a viral syndrome, gastroenteritis, psychiatric disorders, or neck strain.[53-57,68,69] Undue focus on associated findings–abnormal electrocardiogram, dysrhythmia, head injury (from syncope) or elevated blood pressure–may divert attention from the true cause of the symptoms.[64,70] The headache may improve or resolve with non-narcotic analgesics, including sumatriptan, so diagnostic significance ought not to be ascribed to improvement with medications.[71-74] Headache from so-called warning (or sentinel) bleeds can remit spontaneously. On the other end of the spectrum, occasional patients with SAH who present with cardiac arrest can have excellent outcomes.[75,76]
Understanding the full spectrum of presentation of SAH is the best strategy to avoid misdiagnosis.[2,3,64] Once the physician decides to perform a work-up, the next steps–CT scanning and LP–are straightforward.
CT Scanning
The standard first test, unenhanced cranial CT scan (Figure 2), is highly accurate, but like all tests, possesses limitations.[77] Firstly, accuracy decays with time; this is due to circulation of cerebrospinal fluid (CSF) and the resultant dilution and catabolism of the blood. Studies using third-generation scanners demonstrate sensitivities in the range of 90–98% within the first 24 h.[11,78-80] One preliminary report of 913 neurologically intact patients (75 with SAH) with severe, abrupt-onset headaches found CT scan to be 92% sensitive and 100% specific; in the 305 patients scanned within 6 h of headache onset, CT scan was 100% sensitive (95% confidence interval 92–100).[81] By 3 and 7 days after the ictus, the sensitivity falls to 85% and 50%, respectively.[82,83] One report using "5th generation" multi-detector CT scanners showed that no SAH case was missed; however, the study was underpowered, which yielded a lower 95% confidence interval of only 61%.[84]
|
|
Figure 2. Imaging from patients with SAH. The top panel of three images shows a CT scan, 3-D angiogram showing two aneurysms (arrows) off the anterior communicating artery (one projecting to the left, the other projecting upwards, and partially obscured by the anterior communicating arteries also traveling upwards), and last, a post-operative angiogram with two clips obliterating both aneurysms. The bottom panel of three images shows similar images of another anterior communicating aneurysm that has been coiled, the third panel being an immediate post-operative study showing that the aneurysm is completely obliterated. The CT scan from the top panel is more subtly abnormal than the CT scan on the bottom panel, which shows much more blood. |
Until more convincing data confirm the 100% sensitivity of ultra-early or ultra-modern CT scanning in SAH, all patients being evaluated for SAH whose CT scans are normal, technically inadequate, or non-diagnostic, should undergo LP.[2,77]
Lumbar Puncture
Cerebrospinal fluid (CSF) analysis also has limitations. Traumatic taps–red blood cells (RBCs) resulting from needle trauma–occur 10–15% of the time.[96] Fluoroscopically guided LP may decrease this but is not routinely available.[97] None of the methods of distinguishing traumatic taps from SAH is foolproof.[98] Like the CT scan, CSF findings evolve over time from onset of symptoms.
Blood from ruptured aneurysms rapidly disseminates throughout the subarachnoid space, and large numbers of RBCs are present in the lumbar theca within 2–4 h.[99] The development of xanthochromia, the yellowish hue resulting from hemoglobin catabolism into oxyhemoglobin, methemoglobin, and bilirubin, requires more time. Presence of xanthochromia indicates that the CSF contains blood that has undergone in vivo enzymatic degradation to bilirubin, implying true SAH.[100] However, oxyhemoglobin can form in vitro, and experimentally, traumatic taps can result in discolored fluid from oxyhemoglobin.[101]
Xanthochromia can be measured visually (Figure 3) or by spectrophotometry, the latter being clearly more sensitive.[75,76,102-107] Some recommend exclusively using spectrophotometry, based on a study of 111 patients with CT-proven SAH, in which all subjects had spectrophotometrically measured xanthochromia from 12 h until 2 weeks after onset of headache.[108,109,110] More recently, investigators studied the more clinically relevant population of CT-negative patients. Of 463 patients, CSF spectrophotometry found 2% had symptomatic aneurysms.[111] Unfortunately, this retrospective chart review did not report the percentage of patients with visually measured xanthochromia, the timing of the LP, or the CSF RBC counts.
|
|
Figure 3. Xanthochromia can be measured visually or by spectrophotometry. These images show the appearance of visually measured xanthochromic cerebrospinal fluid (CSF). Technique is still important when measuring visually. Hand carry the CSF to the laboratory, rapidly centrifuge the tube, and then compare the supernatant to an identical tube filled with an equal volume of water. Note that the ambient lighting may change the ease with which one can see the color change; the top two panels are of the same specimen seen in different lighting. Some specimens (bottom panel) are more obvious than others. (This figure may be viewed in color in the web version of this article.) |
However it is assessed, xanthochromia takes time to develop. By spectrophotometry, it can take as long as 12 h; however, even by visual inspection, xanthochromia often develops earlier.[99,110] Unfortunately, there are no well-performed clinical studies to allow clinicians to confidently know what the false-negative rate for xanthochromia is at specific time intervals from the bleed. To assess for xanthochromia, the CSF should be rapidly centrifuged and (in the case of spectrophotometry) stored in darkness. When measured visually, the CSF should be carefully compared to an identical tube filled with an equal volume of tap water against a white background. Spectrophotometric measurement should focus on the presence of bilirubin.[111,115]
Importantly, early-presenting patients without xanthochromia will all have large amounts of RBCs in the CSF. The rare exceptions (intraparenchymal or subdural rupture or spinal block) will have positive CT scans.[116-119] Two other useful, albeit imperfect, methods to distinguish traumatic taps from true bleeds are the "3-tube" test and measuring the opening pressure of the CSF.[98] In the former, one looks for diminishing numbers of RBCs from the first to the last tube trending toward zero. This last detail is crucial. Older literature shows that a "decrease" (undefined) does not discriminate between traumatic tap and true SAH.[120] In a more recent study using an arbitrary cutoff of a 25% reduction from tube 1 to 4, 2 of 8 patients had aneurysms.[121] Thus, a simple decrease is insufficient to exclude SAH and the last tube RBC count should approach zero. When bloody fluid is identified, wasting 2–3 mL of CSF to increase the gap between the first and last tubes improves the odds that the last tube RBC count will approach zero.[98] There is no specific number of RBCs that serves as a threshold amount and the rate of RBC clearance is variable.
The opening pressure, which is elevated in two-thirds of SAH patients and is normal in traumatic taps, should also be measured.[99] Elevated pressure also suggests the alternative diagnosis of cerebral venous sinus thrombosis or idiopathic intracranial hypertension, and abnormally low pressure suggests spontaneous intracranial hypotension.[2,122,123]
Other Diagnostic Issues
Primary Use of CT Angiography for Diagnosis of SAH
With the increasing availability of multi-detector CT scanners, some have recommended using CT angiography (CTA) to diagnose SAH.[124] Of the 116 patients, 6 (5.1%) had aneurysms (with normal CT but positive CSF findings); these patients would have been identified by the standard work-up. Three had positive CTA with normal CT and CSF, but these patients more likely had asymptomatic aneurysms with a headache of another benign cause. Like with spectrophotometry, a strategy of primary CTA for diagnosis of SAH would be expected to subject many patients to unnecessary work-ups, procedures, and angiographic contrast material.
MR for Primary Diagnosis of SAH
Magnetic resonance (MR) technology is constantly advancing and shows promise for SAH diagnosis.[125] Although fluid-attenuated inversion recovery (FLAIR) and T2-graded echo MR may be better than CT for detection of chronic subarachnoid blood and possibly equivalent for intraparenchymal hemorrhage, false positives have been documented in acute SAH with both techniques.[126-128] One recent study showed that all 13 patients (with positive CT scans) tested within 12 h of symptom-onset by MR (FLAIR and proton-density weighted) were MR positive.[129] However, another study showed that of 12 patients with SAH (and negative CT scans), only 2 of the 12 (the 2 with the highest RBC counts) had positive FLAIR MR for SAH, showing that spectrum bias exists with MR as well.[128] No large studies of MR diagnosis in unselected headache patients exist. Therefore, CT, which is quicker, cheaper, more readily available and easier to interpret, remains the diagnostic study of choice. If one uses MR, communication with the radiologist is critical to ensure acquisition of the correct sequences.
LP-first Strategy
Some have advocated an LP-first strategy in patients with severe acute headache, normal vital signs, and physical examinations.[130] The rationale is that in practice, physicians evaluating patients for SAH often omit the LP after a negative CT scan.[11,131] An LP-first strategy forces the LP to be done and would consume fewer resources.
An LP-first strategy may be safe, even in H&H Grade 2 and 3 patients, who have meningismus and may be drowsy.[132,133] However, this practice can be dangerous, because collecting CSF in SAH patients may precipitate rebleeding or herniation from an unrecognized intracranial hematoma, which can occur in the absence of localizing neurological findings.[134,135] Most of the patients who deteriorated in these latter two studies had neck stiffness and were H&H grade 1–3 (mostly 2), although one patient had no meningismus.[135]
Therefore, an LP-first strategy is likely safe in carefully selected patients who are neurologically normal and without signs of elevated ICP. On the other hand, this approach would be contraindicated in patients with any kind of neurological abnormalities on examination or those with symptoms or signs of high ICP. Unfortunately, there are no clinical trials that assist clinicians in selecting patients for this approach, and the CT scan followed by LP remains the standard diagnostic sequence.
When to Stop the Work-up?
In patients with acute, severe headache and normal neurological examinations, CT scans, and CSF analysis, is further evaluation necessary? The vast majority of such patients have excellent outcomes. In one retrospective study of 71 patients, none had SAH during an average follow-up of 3.3 years.[136] Furthermore, in four prospective studies (totaling 254 patients) followed for over 1 year, none had subsequent SAH or sudden death.[9,137-139] This evidence strongly suggests that most patients with normal CT and CSF examinations do not require angiography. The occasional patient whose clinical presentation suggests cranial artery dissection, cerebral venous sinus thrombosis, or pituitary apoplexy may require further imaging.
"Warning" or "Sentinel" SymptomsSome patients with SAH report unusual, severe headaches in the weeks preceding their SAH diagnosis–a phenomenon loosely described in the literature as "warning" or "sentinel" "headache" or "bleed." A recent systematic review found that such headaches occur in 10–43% of cases of SAH.[140] Possible explanations for these episodes include a) initial misdiagnosis of a true SAH (either by the patient or the physician), b) recall bias of patients being admitted for a serious neurological problem, or c) pain from symptomatic but unruptured aneurysms.[2,140-143] Recall bias may account for a small fraction of cases.[140,144] The most likely explanation, supported by histological evidence in one case, is that most instances represent small undiagnosed SAHs.[145] Data supporting this hypothesis are mixed, with one study suggesting no worse outcomes in patients returning after a "warning" event and another showing worse outcomes.[142,144] Whatever the correct explanation, aggressive evaluation of patients with acute-onset severe headache should reduce the phenomenon of delayed or missed diagnosis.
Symptomatic Unruptured Aneurysms
The vast majority of unruptured aneurysms are asymptomatic, but occasional patients have thunderclap headache from intact aneurysms that are acutely expanding, dissecting, or thrombosing.[2] Other symptoms of unruptured aneurysms include transient cerebral ischemia, gradual-onset headache, seizure, or mass effect.[2,53,143] The classic mass lesion is a third cranial nerve palsy, an important syndrome for emergency physicians to understand.[99,146,147]
Initial Management Considerations
Once the diagnosis of SAH is established, the priority shifts to definitive therapy, prevention of complications, and consultation with a skilled cerebrovascular specialist. This discussion between specialist and emergency physician should address several issues, including airway control, treatment of acute hydrocephalus, blood pressure control, seizure and vasospasm prophylaxis, and others ( Table 4 ).[148,149] In this age of endovascular treatment, disposition of patients with SAH needs reevaluation because data suggest that SAH patients do better when treated in high-volume centers that offer both surgical and endovascular approaches.[150-153]
Cerebrovascular Imaging
Upon diagnosis of SAH, cerebrovascular imaging is obtained as soon as possible after stabilization. A high-quality four-vessel cerebral digital subtraction angiogram (DSA) usually elucidates the etiology of the SAH. Negative angiograms occur with perimesencephalic hemorrhage, thrombosed aneurysms, or in cases of severe parent vessel spasm, which can interfere with aneurysmal filling. In the case of intracranial aneurysm, two- or newer three-dimensional angiography demonstrates the size and location of the aneurysm very well (Figure 2).[154] Modern DSA is very safe, one prospective series of nearly 3000 procedures showing a complication rate of only 1.3%, more than half of which were transient or reversible.[155]
Although DSA remains the gold standard, multi-detector CT angiography demonstrates high sensitivity and specificity.[156-160] Four studies have evaluated a strategy of CTA-only for planning the surgical approach in large numbers of patients with SAH.[161-164] Other investigators have accumulated experience with surgical planning based exclusively on MR angiography.[165,166] Occasionally, both CT and MR angiography miss small aneurysms, and evidence suggests that neuroradiologists' interpretations may be superior to others.[156,160,167,168] As of 2007, the choice of cerebrovascular imaging study is evolving and should be left to the discretion of the consultant.
RebleedingRebleeding, an important cause of poor outcomes, occurs in 4% of patients in the first 24 h after hemorrhage, and approximately 1.5% per day for up to 2 weeks after the initial hemorrhage, yielding a total re-hemorrhage rate of 26.5% over the first 2 weeks after the INITIAL BLEED.[169-171] At one referral center, 40 of 574 (6.9%) patients rebled in the first 3 days post-ictus.[172] Those who rebled had higher H&H grades, larger aneurysms, and worse outcomes. Therefore, strategies to reduce rebleeding are critical.
Although few data suggest that aggressively lowering blood pressure prevents rebleeding, most treating physicians insert an arterial catheter and use intravenous agents to maintain adequate cerebral perfusion in the patient with elevated intracranial pressure and in elderly patients with pre-existing atherosclerosis or hypertension.[173] These steps are generally initiated in the intensive care unit. Also, because there is no good evidence to suggest the proper target blood pressure, this choice is generally left to the consultant. The most common anti-hypertensive agents used are labetolol, nicardipine, and nitroprusside. Again, there are no head-to-head clinical trials to compare these agents. Treatment of pain and anxiety may also help to reduce elevated blood pressure.
In the past, when surgery was delayed by weeks, antifibrinolytics (epsilon-aminocaproic acid and tranexamic acid) were used to reduce rebleeding. A recent review concluded that these agents were not routinely indicated because the price for the reduction in rebleeding was increased ischemic deficits from vasospasm.[174] Current trends toward early aneurysm obliteration have reduced the need for long-term antifibrinolytic use. However, there has been renewed interest in using short-term antifibrinolytics from the time of diagnosis to the time of definitive treatment, even if this interval is only several hours.[175] A randomized prospective multi-center trial using short-term tranexamic acid suggested that this strategy reduced rebleeding without increasing vasospasm or clinically significant cerebral ischemia.[176]
Hydrocephalus
Hydrocephalus occurs in up to 33–50% of all patients with SAH, and is more likely to occur with larger volume hemorrhages. Acute (early) hydrocephalus from intraventricular blood that occludes the foramen of Monroe or Luschka, obstructing CSF outflow, occurs in approximately 20% of patients.[17,177] Importantly, this cause of coma after SAH is reversible by treatment with emergent ventriculostomy.
Vasospasm and Delayed Cerebral Ischemia
Cerebral vasospasm typically develops several days after the initial SAH, peaking 7–10 days after the hemorrhage and lasting up to 2 weeks.[17] The risk of developing vasospasm is related to the density of blood at the time of initial ictus.[178,179] Vasospasm may be an asymptomatic angiographic phenomenon, or it may lead to symptomatic delayed cerebral ischemia (DCI), which is an important cause of morbidity after SAH. The resulting infarctions, which may be asymptomatic, may be distant from the site of the offending aneurysm or involve watershed distributions.[180] Emergency physicians should be aware of this fact because some patients will present during this phase.
Prophylactic use of nimodipine improves outcomes, although the mechanism remains unclear.[181] Some preliminary data suggest that intravenous magnesium sulfate may reduce DCI and poor outcomes, but further research is needed to confirm these findings.[182]
If vasospasm is confirmed or suspected in the presence of neurological deterioration, "triple H" therapy (hypertension, hemodilution, and hypervolemia) may be instituted.[183] Although a recent Cochrane review concluded that there is no convincing evidence supporting it, triple-H therapy is commonly used in practice.[183-185] If medical therapy fails, various endovascular strategies also may be employed.[186-190] These therapies underscore the advantages of a high-volume neurovascular center.
Aneurysm Obliteration
Early treatment of the ruptured aneurysm is the currently accepted strategy at most centers today. Occasionally, extenuating circumstances such as unstable medical conditions that preclude safe surgery or high-grade patients with poor prognosis may delay treatment. However, the goal in most patients is to obliterate the aneurysm within 1–3 days after the hemorrhage with either microsurgical aneurysm clipping or endovascular coil embolization (Figure 2).
Intracranial microsurgical clipping is a technique that has evolved considerably since its introduction in the 1970s with the advent of the stereoscopic high-magnification microscope. Using microsurgical techniques, the neurosurgeon opens the dura and identifies the parent vessel and the ruptured aneurysm, which is then clipped to exclude it from the circulation. The durability of successful surgical clipping is high, with a follow-up study showing aneurysm recurrence rate of 2–3%.[191]
Endovascular coiling uses a micro-catheter that is threaded through a guide catheter to the origin of the ruptured aneurysm. Once inside the aneurysm, platinum coils are gently inserted into the sac in a sequential outside-in multi-layered fashion until the aneurysm is densely packed. This process relies on a critical volume of embolization and also requires that the aneurysm inflow zone be securely occluded to deflect blood from entering the aneurysm. Although wide-necked aneurysms were initially considered poor candidates for coil embolization, newer techniques have expanded the pool of endovascular candidates.[192-194]
Patients treated with coil therapy require serial monitoring and follow-up cerebrovascular imaging to detect the occasional risk of coil compaction or aneurysm recanalization, which can occur in larger size wide-necked or poorly packed aneurysms. Initial treatment yields up to 70% of patients experiencing 95–100% occlusion of the aneurysm. However, 25–30% of patients do not have complete obliteration of the aneurysm, and recanalization can occur.[195]
The decision to proceed with open surgical clipping or endovascular treatment of an intracranial aneurysm after SAH rests on aneurysm-specific factors (location, size, morphology, and presence of thrombus) and patient-specific factors (age, density of SAH, patient preference, and other medical comorbidities).
The International Subarachnoid Aneurysm Trial randomized 2143 SAH patients whose aneurysms were judged to be equally suitable for surgical clipping or endovascular coiling to be treated surgically vs. endovascularly.[196] Due to the selection criteria, patients were typically in good pre-treatment condition and there was a preponderance of anterior circulation aneurysms. Using a modified Rankin scale at 1 year as the outcome measure, the International Subarachnoid Aneurysm Trial demonstrated a statistically significant relative risk reduction of 22.6% and an absolute risk reduction of 6.9% in favor of endovascularly treated patients. Follow-up (1 to 7 years) revealed durability of these outcomes. The endovascularly treated patients had fewer seizures but (while low), more rebleeding.[197] Similar results have been obtained in other studies.[198]
Ideally, high-quality endovascular and surgical techniques will be available at a neurovascular center, which allows for the best treatment decisions to be made on a case-by-case basis.[153] Whether treated endovascularly or surgically, patients are closely monitored for blood pressure, cardiac, renal, and respiratory function by a multi-disciplinary team with close neurological monitoring to detect DCI.
ConclusionsEmergency physicians must be vigilant in evaluating patients with symptoms consistent with SAH or otherwise symptomatic aneurysms. This evaluation must take place with an understanding of the limitations of the diagnostic tests used. Attention to early complications and prompt referral to centers where there are teams with cerebrovascular expertise will maximize the options available to these patients.
eferences
1. Goldstein JN, Camargo CA, Pelletier AJ, Edlow JA. Headache in United States Emergency Departments: demographics, work-up and frequency of pathological diagnoses. Cephalalgia. 2006;26:684–690.2. Edlow JA, Caplan LR. Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage. N Engl J Med. 2000;342:29–36.
3. Edlow JA. Diagnosis of subarachnoid hemorrhage. Neurocrit Care. 2005;2:99–109.
4. Rinkel GJ, van Gijn J, Wijdicks EF. Subarachnoid hemorrhage without detectable aneurysm (A review of the causes). Stroke. 1993;24:1403–1409.
5. van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet. 2007;369:306–318.
6. Dhopesh V, Anwar R, Herring C. A retrospective assessment of emergency department patients with complaints of headache. Headache. 1979;19:37–42.
7. Leicht M. Non-traumatic headache in the emergency department. Ann Emerg Med. 1980;9:404–409.
8. Ramirez-Lassepas M, Espinosa CE, Cicero JJ, Johnston KL, Cipolle RJ, Barber DL. Predictors of intracranial pathologic findings in patients who seek emergency care because of headache. Arch Neurol. 1997;54:1506–1509.
9. Landtblom AM, Fridriksson S, Boivie J, Hillman J, Johansson G, Johansson I. Sudden onset headache: a prospective study of features, incidence and causes. Cephalalgia. 2002;22:354–360.
10. Linn FH, Rinkel GJ, Algra A, van Gijn J. Incidence of subarachnoid hemorrhage: role of region, year, and rate of computed tomography: a meta-analysis. Stroke. 1996;27:625–629.
11. Morgenstern LB, Luna-Gonzales H, Huber JC, et al.. Worst headache and subarachnoid hemorrhage: prospective, modern computed tomography and spinal fluid analysis. Ann Emerg Med. 1998;32:297–304.
12. Perry JJ, Stiell IG, Wells GA, et al.. Attitudes and judgment of emergency physicians in the management of patients with acute headache. Acad Emerg Med. 2005;12:33–37.
13. Schievink WI. Intracranial aneurysms. N Engl J Med. 1997;336:28–40.
14. Johansson A, Lagerstedt K, Asplund K. Mishaps in the management of stroke: a review of 214 complaints to a medical responsibility board. Cerebrovasc Dis. 2004;18:16–21.
15. Karcz A, Holbrook J, Burke M, et al.. Massachusetts emergency medicine closed malpractice claims: 1988–1990. Ann Emerg Med. 1993;22:553–559.
16. Rinkel GJ, Djibuti M, Algra A, van Gijn J. Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke. 1998;29:251–256.
17. Weir B. Diagnostic aspects of subarachnoid hemorrhage. In: Weir B editors. Subarachnoid hemorrhage: causes and cures. New York: Oxford University Press; 1998;p. 144–176.
18. Wiebers DO, Whisnant JP, Huston J, et al.. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362:103–110.
19. Ujiie H, Tachibana H, Hiramatsu O, et al.. Effects of size and shape (aspect ratio) on the hemodynamics of saccular aneurysms: a possible index for surgical treatment of intracranial aneurysms. Neurosurgery. 1999;45:119–129; discussion 129–30.
20. Nader-Sepahi A, Casimiro M, Sen J, Kitchen ND. Is aspect ratio a reliable predictor of intracranial aneurysm rupture?. Neurosurgery. 2004;54:1343–1347; discussion 1347–8.
21. Beck J, Rohde S, el Beltagy M, et al.. Difference in configuration of ruptured and unruptured intracranial aneurysms determined by biplanar digital subtraction angiography. Acta Neurochir (Wien). 2003;145:861–865.
22. Huang J, van Gelder JM. The probability of sudden death from rupture of intracranial aneurysms: a meta-analysis. Neurosurgery. 2002;51:1101–1105; discussion 1105–7.
23. Epidemiology of aneurysmal subarachnoid hemorrhage in Australia and New Zealand. incidence and case fatality from the Australasian Cooperative Research on Subarachnoid Hemorrhage Study (ACROSS). Stroke. 2000;31:1843–1850.
24. Olafsson E, Hauser WA, Gudmundsson G. A population-based study of prognosis of ruptured cerebral aneurysm: mortality and recurrence of subarachnoid hemorrhage. Neurology. 1997;48:1191–1195.
25. Pobereskin LH. Incidence and outcome of subarachnoid haemorrhage: a retrospective population based study. J Neurol Neurosurg Psychiatry. 2001;70:340–343.
26. Schievink WI, Wijdicks EF, Parisi JE, Piepgras DG, Whisnant JP. Sudden death from aneurysmal subarachnoid hemorrhage. Neurology. 1995;45:871–874.
27. Stegmayr B, Eriksson M, Asplund K. Declining mortality from subarachnoid hemorrhage: changes in incidence and case fatality from 1985 through 2000. Stroke. 2004;35:2059–2063.
28. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg. 1968;28:14–20.
29. Lindsay KW, Teasdale G, Knill-Jones RP, Murray L. Observer variability in grading patients with subarachnoid hemorrhage. J Neurosurg. 1982;56:628–633.
30. Teasdale GM, Drake CG, Hunt W, et al.. A universal subarachnoid hemorrhage scale: report of a committee of the World Federation of Neurosurgical Societies. J Neurol Neurosurg Psychiatry. 1988;51:1457.
31. Oshiro EM, Walter KA, Piantadosi S, Witham TF, Tamargo RJ. A new subarachnoid hemorrhage grading system based on the Glasgow Coma Scale: a comparison with the Hunt and Hess and World Federation of Neurological Surgeons Scales in a clinical series. Neurosurgery. 1997;41:140–147; discussion 147–8.
32. Ogilvy CS, Carter BS. A proposed comprehensive grading system to predict outcome for surgical management of intracranial aneurysms. Neurosurgery. 1998;42:959–968; discussion 968–70.
33. Frykholm P, Andersson JL, Langstrom B, Persson L, Enblad P. Haemodynamic and metabolic disturbances in the acute stage of subarachnoid haemorrhage demonstrated by PET. Acta Neurol Scand. 2004;109:25–32.
34. Tung P, Kopelnik A, Banki N, et al.. Predictors of neurocardiogenic injury after subarachnoid hemorrhage. Stroke. 2004;35:548–551.
35. Schuiling WJ, Dennesen PJ, Tans JT, Kingma LM, Algra A, Rinkel GJ. Troponin I in predicting cardiac or pulmonary complications and outcome in subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2005;76:1565–1569.
36. Andreoli A, di Pasquale G, Pinelli G, Grazi P, Tognetti F, Testa C. Subarachnoid hemorrhage: frequency and severity of cardiac dysrhythmias (A survey of 70 cases studied in the acute phase). Stroke. 1987;18:558–564.
37. Naidech AM, Kreiter KT, Janjua N, et al.. Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage. Circulation. 2005;112:2851–2856.
38. Urbaniak K, Merchant AI, Amin-Hanjani S, Roitberg B. Cardiac complications after aneurysmal subarachnoid hemorrhage. Surg Neurol. 2007;67:21–28; discussion 28–9.
39. Labovitz DL, Halim AX, Brent B, Boden-Albala B, Hauser WA, Sacco RL. Subarachnoid hemorrhage incidence among Whites, Blacks and Caribbean Hispanics: the Northern Manhattan Study. Neuroepidemiology. 2006;26:147–150.
40. Rothwell PM, Coull AJ, Giles MF, et al.. Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). Lancet. 2004;363:1925–1933.
41. Sivenius J, Tuomilehto J, Immonen-Raiha P, et al.. Continuous 15-year decrease in incidence and mortality of stroke in Finland: the FINSTROKE study. Stroke. 2004;35:420–425.
42. Nilsson OG, Lindgren A, Stahl N, Brandt L, Saveland H. Incidence of intracerebral and subarachnoid haemorrhage in southern Sweden. J Neurol Neurosurg Psychiatry. 2000;69:601–607.
43. Inagawa T. Trends in incidence and case fatality rates of aneurysmal subarachnoid hemorrhage in Izumo City, Japan, between 1980–1989 and 1990–1998. Stroke. 2001;32:1499–1507.
44. Juvela S. Prevalence of risk factors in spontaneous intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage. Arch Neurol. 1996;53:734–740.
45. Ruigrok YM, Buskens E, Rinkel GJ. Attributable risk of common and rare determinants of subarachnoid hemorrhage. Stroke. 2001;32:1173–1175.
46. Teunissen LL, Rinkel GJ, Algra A, van Gijn J. Risk factors for subarachnoid hemorrhage: a systematic review. Stroke. 1996;27:544–549.
47. Johnston SC, Colford JM, Gress DR. Oral contraceptives and the risk of subarachnoid hemorrhage: a meta-analysis. Neurology. 1998;51:411–418.
48. Feigin VL, Rinkel GJ, Lawes CM, et al.. Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies. Stroke. 2005;36:2773–2780.
49. Raaymakers TWMARS Study Group. Aneurysms in relatives of patients with subarachnoid hemorrhage: frequency and risk factors (Magnetic Resonance Angiography in Relatives of patients with Subarachnoid hemorrhage). Neurology. 1999;53:982–988.
50. Ronkainen A, Hernesniemi J, Puranen M, et al.. Familial intracranial aneurysms. Lancet. 1997;349:380–384.
51. Fessler RD, Esshaki CM, Stankewitz RC, Johnson RR, Diaz FG. The neurovascular complications of cocaine. Surg Neurol. 1997;47:339–345.
52. Schievink WI, Michels VV, Piepgras DG. Neurovascular manifestations of heritable connective tissue disorders (A review). Stroke. 1994;25:889–903.
53. Adams HP, Jergenson DD, Kassell NF, Sahs AL. Pitfalls in the recognition of subarachnoid hemorrhage. JAMA. 1980;244:794–796.
54. Kassell N, Kongable G, Torner J, Adams H, Mazuz H. Delay in referral of patients with ruptured aneurysms to neurosurgical attention. Stroke. 1985;16:587–590.
55. Kowalski RG, Claassen J, Kreiter KT, et al.. Initial misdiagnosis and outcome after subarachnoid hemorrhage. JAMA. 2004;291:866–869.
56. Mayer PL, Awad IA, Todor R, et al.. Misdiagnosis of symptomatic cerebral aneurysm: prevalence and correlation with outcome at four institutions. Stroke. 1996;27:1558–1563.
57. Neil-Dwyer G, Lang D. 'Brain attack'–aneurysmal subarachnoid haemorrhage: death due to delayed diagnosis. J R Coll Physicians Lond. 1997;31:49–52.
58. Vannemreddy P, Nanda A, Kelley R, Baskaya MK. Delayed diagnosis of intracranial aneurysms: confounding factors in clinical presentation and the influence of misdiagnosis on outcome. South Med J. 2001;94:1108–1111.
59. Fridriksson S, Hillman J, Landtblom AM, Boive J. Education of referring doctors about sudden onset headache in subarachnoid hemorrhage (A prospective study). Acta Neurol Scand. 2001;103:238–242.
60. Miyazaki T, Ohta F, Moritake K, Nagase A, Kagawa T. The key to improving prognosis for aneurysmal subarachnoid hemorrhage remains in the pre-hospitalization period. Surg Neurol. 2006;65:360–365, discussion 365–6.
61. Vermeulen MJ, Schull MJ. Missed diagnosis of subarachnoid hemorrhage in the emergency department. Stroke. 2007;38:1216–1221.
62. Edlow JA. Diagnosis of subarachnoid hemorrhage: are we doing better?. Stroke. 2007;38:1129–1131.
63. Linn FH, Wijdicks EF. Causes and management of thunderclap headache: a comprehensive review. Neurologist. 2002;8:279–289.
64. Edlow JA. Diagnosis of subarachnoid hemorrhage in the emergency department. Emerg Med Clin North Am. 2003;21:73–87.
65. Rosenorn J, Eskesen V, Schmidt K, et al.. Clinical features and outcome in 1076 patients wtih ruptured intracranial saccular aneurysms: a prospective consecutive study. Br J Neurosurg. 1987;1:33–46.
66. Schievink WI, Karemaker JM, Hageman LM, van der Werf DJ. Circumstances surrounding aneurysmal subarachnoid hemorrhage. Surg Neurol. 1989;32:266–272.
67. Fann JR, Kukull WA, Katon WJ, Longstreth WT. Physical activity and subarachnoid haemorrhage: a population based case-control study. J Neurol Neurosurg Psychiatry. 2000;69:768–772.
68. Reijneveld JC, Wermer M, Boonman Z, van Gijn J, Rinkel GJ. Acute confusional state as presenting feature in aneurysmal subarachnoid hemorrhage: frequency and characteristics. J Neurol. 2000;247:112–116.
69. Caeiro L, Menger C, Ferro JM, Albuquerque R, Figueira ML. Delirium in acute subarachnoid haemorrhage. Cerebrovasc Dis. 2005;19:31–38.
70. Asplin BR, White RD. Subarachnoid hemorrhage: atypical presentation associated with rapidly changing cardiac arrhythmias. Am J Emerg Med. 1994;12:370–373.
71. Seymour JJ, Moscati RM, Jehle DV. Response of headaches to nonnarcotic analgesics resulting in missed intracranial hemorrhage. Am J Emerg Med. 1995;13:43–45.
72. Rosenberg JH, Silberstein SD. The headache of SAH responds to sumatriptan. Headache. 2005;45:597–598.
73. Rothrock J. The perils of misinterpreting a treatment response. Headache. 2005;45:599–600.
74. Pfadenhauer K, Schonsteiner T, Keller H. The risks of sumatriptan administration in patients with unrecognized subarachnoid haemorrhage (SAH). Cephalalgia. 2006;26:320–323.
75. Toussaint LG, Friedman JA, Wijdicks EF, et al.. Survival of cardiac arrest after aneurysmal subarachnoid hemorrhage. Neurosurgery. 2005;57:25–31.
76. Tabbaa MA, Ramirez-Lassepas M, Snyder BD. Aneurysmal subarachnoid hemorrhage presenting as cardiorespiratory arrest. Arch Intern Med. 1987;147:1661–1662.
77. Edlow JA, Wyer PC. How good is a negative cranial computed tomographic scan result in excluding subarachnoid hemorrhage?. Ann Emerg Med. 2000;36:507–516.
78. Sames TA, Storrow AB, Finkelstein JA, Magoon MR. Sensitivity of new-generation computed tomography in subarachnoid hemorrhage. Acad Emerg Med. 1996;3:16–20.
79. Sidman R, Connolly E, Lemke T. Subarachnoid hemorrhage diagnosis: lumbar puncture is still needed when the computed tomography scan is normal. Acad Emerg Med. 1996;3:827–831.
80. van der Wee N, Rinkel GJ, Hasan D, van Gijn J. Detection of subarachnoid haemorrhage on early CT: is lumbar puncture still needed after a negative scan?. J Neurol Neurosurg Psychiatry. 1995;58:357–359.
81. Perry JJ, Stiell IG, Wells GA, et al.. The sensitivity of CT for the diagnosis of subarachnoid hemorrhage in ED patients with acute headache. Acad Emerg Med. 2004;11:435–436.
82. Kassell NF, Torner JC, Haley EC, Jane JA, Adams HP, Kongable GL. The International Cooperative Study on the Timing of Aneurysm Surgery (Part 1: overall management results). J Neurosurg. 1990;73:18–36.
83. van Gijn J, van Dongen K. The time course of aneurysmal haemorrhage on computed tomograms. Neuroradiology. 1982;23:153–156.
84. Boesiger BM, Shiber JR. Subarachnoid hemorrhage diagnosis by computed tomography and lumbar puncture: are fifth generation CT scanners better at identifying subarachnoid hemorrhage?. J Emerg Med. 2005;29:23–27.
85. Smith WP, Batnitzky S, Rengachary SS. Acute isodense subdural hematomas: a problem in anemic patients. AJR Am J Roentgenol. 1981;136:543–546.
86. Schriger D, Kalafut M, Starkman S, Krueger M, Saver J. Cranial computed tomography interpretation in acute stroke. JAMA. 1998;279:1293–1297.
87. Chatterjee T, Gowardman JR, Goh TD. Pneumococcal meningitis masquerading as subarachnoid haemorrhage. Med J Aust. 2003;178:505–507.
88. Given CA, Burdette JH, Elster AD, Williams DW. Pseudo-subarachnoid hemorrhage: a potential imaging pitfall associated with diffuse cerebral edema. AJNR Am J Neuroradiol. 2003;24:254–256.
89. Huang D, Abe T, Ochiai S, et al.. False positive appearance of subarachnoid hemorrhage on CT with bilateral subdural hematomas. Radiat Med. 1999;17:439–442.
90. Mendelsohn DB, Moss ML, Chason DP, Muphree S, Casey S. Acute purulent leptomeningitis mimicking subarachnoid hemorrhage on CT. J Comput Assist Tomogr. 1994;18:126–128.
91. Rabinstein AA, Pittock SJ, Miller GM, Schindler JJ, Wijdicks EF. Pseudosubarachnoid haemorrhage in subdural haematoma. J Neurol Neurosurg Psychiatry. 2003;74:1131–1132.
92. Sharp S, Stone J, Beach R. Contrast agent neurotoxicity presenting as subarachnoid hemorrhage. Neurology. 1999;52:1503–1505.
93. Schievink WI, Maya MM, Tourje J, Moser FG. Pseudo-subarachnoid hemorrhage: a CT-finding in spontaneous intracranial hypotension. Neurology. 2005;65:135–137.
94. Spiegel SM, Fox AJ, Vinuela F, Pelz DM. Increased density of tentorium and falx: a false positive CT sign of subarachnoid hemorrhage. Can Assoc Radiol J. 1986;37:243–247.
95. Velden J, Milz P, Winkler F, Seelos K, Hamann GF. Nonionic contrast neurotoxicity after coronary angiography mimicking subarachnoid hemorrhage. Eur Neurol. 2003;49:249–251.
96. Shah KH, Richard KM, Nicholas S, Edlow JA. Incidence of traumatic lumbar puncture. Acad Emerg Med. 2003;10:151–154.
97. Eskey CJ, Ogilvy CS. Fluoroscopy-guided lumbar puncture: decreased frequency of traumatic tap and implications for the assessment of CT-negative acute subarachnoid hemorrhage. AJNR Am J Neuroradiol. 2001;22:571–576.
98. Shah KH, Edlow JA. Distinguishing traumatic lumbar puncture from true subarachnoid hemorrhage. J Emerg Med. 2002;23:67–74.
99. Walton J. Subarachnoid hemorrhage. Edinburgh: E & S Livingstone, Ltd; 1956;.
100. Fishman R. Composition of the cerebrospinal fluid (In: Cerebrospinal fluid in diseases of the central nervous system, 2nd edn). Philadelphia: WB Saunders; 1992;183–252.
101. Graves P, Sidman R. Xanthochromia is not pathognomonic for subarachnoid hemorrhage. Acad Emerg Med. 2004;11:131–135.
102. Soderstrom CE. Diagnostic significance of CSF spectrophotometry and computer tomography in cerebrovascular disease (A comparative study in 231 cases). Stroke. 1977;8:606–612.
103. Petzold A, Keir G, Sharpe TL. Why human color vision cannot reliably detect cerebrospinal fluid xanthochromia. Stroke. 2005;36:1295–1297.
104. Petzold A, Sharpe LT, Keir G. Spectrophotometry for cerebrospinal fluid pigment analysis. Neurocrit Care. 2006;4:153–162.
105. Wood MJ, Dimeski G, Nowitzke AM. CSF spectrophotometry in the diagnosis and exclusion of spontaneous subarachnoid haemorrhage. J Clin Neurosci. 2005;12:142–146.
106. Sidman R, Spitalnic S, Demelis M, Durfey N, Jay G. Xanthrochromia? (By what method? A comparison of visual and spectrophotometric xanthrochromia). Ann Emerg Med. 2005;46:51–55.
107. Beetham R, Fahie-Wilson MN, Park D. What is the role of CSF spectrophotometry in the diagnosis of subarachnoid haemorrhage?. Ann Clin Biochem. 1998;35(Pt 1):1–4.
108. Vermeulen M, van Gijn J. The diagnosis of subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 1990;53:365–372.
109. Vermeulen M. Subarachnoid haemorrhage: diagnosis and treatment. J Neurol. 1996;243:496–501.
110. Vermeulen M, Hasan D, Blijenberg BG, Hijdra A, van Gijn J. Xanthochromia after subarachnoid haemorrhage needs no revisitation. J Neurol Neurosurg Psychiatry. 1989;52:826–828.
111. Gunawardena H, Beetham R, Scolding N, Lhatoo SD. Is cerebrospinal fluid spectrophotometry useful in CT scan-negative suspected subarachnoid haemorrage?. Eur Neurol. 2004;52:226–229.
112. Perry JJ, Sivilotti ML, Stiell IG, et al.. Should spectrophotometry be used to identify xanthochromia in the cerebrospinal fluid of alert patients suspected of having subarachnoid hemorrhage?. Stroke. 2006;37:2467–2472.
113. Edlow JA, Bruner KS, Horowitz GL. Xanthochromia. Arch Pathol Lab Med. 2002;126:413–415.
114. Linn FH, Voorbij HA, Rinkel GJ, Algra A, van Gijn J. Visual inspection versus spectrophotometry in detecting bilirubin in cerebrospinal fluid. J Neurol Neurosurg Psychiatry. 2005;76:1452–1454.
115. Cruickshank AM. ACP Best Practice No 166: CSF spectrophotometry in the diagnosis of subarachnoid haemorrhage. J Clin Pathol. 2001;54:827–830.
116. Roberston E. Cerebral lesions due to intracranial aneurysms. Brain. 1949;72:150–185.
117. Wolfe H. Spontaneous subarachnoid hemorrhage. Br J Surg. 1955;50:319–325.
118. Voris H. Subarachnoid hemorrhage. Ill Med J. 1949;95:160–167.
119. Thai QA, Raza SM, Pradilla G, Tamargo RJ. Aneurysmal rupture without subarachnoid hemorrhage: case series and literature review. Neurosurgery. 2005;57:225–229; discussion 225–9.
120. Buruma OJ, Janson HL, Den Bergh FA, Bots GT. Blood-stained cerebrospinal fluid: traumatic puncture or haemorrhage?. J Neurol Neurosurg Psychiatry. 1981;44:144–147.
121. Heasley DC, Mohamed MA, Yousem DM. Clearing of red blood cells in lumbar puncture does not rule out ruptured aneurysm in patients with suspected subarachnoid hemorrhage but negative head CT findings. AJNR Am J Neuroradiol. 2005;26:820–824.
122. Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006;295:2286–2296.
123. de Bruijn SF, Stam J, Kappelle LJ. Thunderclap headache as first symptom of cerebral venous sinus thrombosis (CVST Study Group). Lancet. 1996;348:1623–1625.
124. Carstairs SD, Tanen DA, Duncan TD, et al.. Computed tomographic angiography for the evaluation of aneurysmal subarachnoid hemorrhage. Acad Emerg Med. 2006;13:486–492.
125. Fiebach JB, Schellinger PD, Geletneky K, et al.. MRI in acute subarachnoid haemorrhage; findings with a standardised stroke protocol. Neuroradiology. 2004;46:44–48.
126. Mitchell P, Wilkinson ID, Hoggard N, et al.. Detection of subarachnoid haemorrhage with magnetic resonance imaging. J Neurol Neurosurg Psychiatry. 2001;70:205–211.
127. Kidwell CS, Chalela JA, Saver JL, et al.. Comparison of MRI and CT for detection of acute intracerebral hemorrhage. JAMA. 2004;292:1823–1830.
128. Mohamed M, Heasly DC, Yagmurlu B, Yousem DM, Heasely DC. Fluid-attenuated inversion recovery MR imaging and subarachnoid hemorrhage: not a panacea. AJNR Am J Neuroradiol. 2004;25:545–550.
129. Wiesmann M, Mayer TE, Yousry I, Medele R, Hamann GF, Bruckmann H. Detection of hyperacute subarachnoid hemorrhage of the brain by using magnetic resonance imaging. J Neurosurg. 2002;96:684–689.
130. Schull MJ. Lumbar puncture first: an alternative model for the investigation of lone acute sudden headache. Acad Emerg Med. 1999;6:131–136.
131. O'Neill J, McLaggan S, Gibson R. Acute headache and subarachnoid haemorrhage: a retrospective review of CT and lumbar puncture findings. Scott Med J. 2005;50:151–153.
132. French JK, Glasgow GL. Lumbar puncture in subarachnoid haemorrhage: yes or no?. N Z Med J. 1985;98:383–384.
133. Patel MK, Clarke MA. Lumbar puncture and subarachnoid haemorrhage. Postgrad Med J. 1986;62:1021–1024.
134. Duffy GP. Lumbar puncture in spontaneous subarachnoid hemorrhage. BMJ. 1982;285:1163–1166.
135. Hillman J. Should computed tomography scanning replace lumbar puncture in the diagostic process in suspected subarachnoid hemorrhage?. Surg Neurol. 1986;26:547–550.
136. Wijdicks EFM, Kerkhoff H, vanGijn J. Long-term follow-up of 71 patients with thunderclap headache mimicking subarachnoid hemorrhage. Lancet. 1988;ii:68–69.
137. Harling DW, Peatfield RC, van Hille PT, Abbot RJ. Thunderclap headache: is it migraine?. Cephalgia. 1989;9:87–90.
138. Linn FH, Wijdicks EF, van der Graaf Y, Weerdesteyn-van Vliet FA, Bartelds AI, van Gijn J. Prospective study of sentinel headache in aneurysmal subarachnoid haemorrhage. Lancet. 1994;344:590–593.
139. Markus HS. A prospective follow-up of thunderclap headache mimicking subarachnoid hemorrhage. J Neurol Neurosurg Psychiatry. 1991;54:1117–1125.
140. Polmear A. Sentinel headaches in aneurysmal subarachnoid haemorrhage: what is the true incidence? (A systematic review). Cephalalgia. 2003;23:935–941.
141. Day JW, Raskin NH. Thunderclap headache: symptom of unruptured cerebral aneurysm. Lancet. 1986;ii:1247–1248.
142. Linn FH, Rinkel GJ, Algra A, van Gijn J. The notion of "warning leaks" in subarachnoid haemorrhage: are such patients in fact admitted with a rebleed?. J Neurol Neurosurg Psychiatry. 2000;68:332–336.
143. Raps EC, Rogers JD, Galetta SL, et al.. The clinical spectrum of unruptured intracranial aneurysm. Arch Neurol. 1993;50:265–268.
144. Beck J, Raabe A, Szelenyi A, et al.. Sentinel headache and the risk of rebleeding after aneurysmal subarachnoid hemorrhage. Stroke. 2006;37:2733–2737.
145. Ball MJ. Pathogenesis of the "sentinel" headache preceding berry aneurysm rupture. Can Med Assoc J. 1975;112:78–79.
146. Sarner M, Rose F. Clinical presentation of ruptured intracranial aneurysm. J Neurol Neurosurg Psychiatry. 1967;30:67–70.
147. Woodruff M, Edlow JA. Evaluation of third nerve palsy in the emergency department. J Emerg Med 2007;Sept 17 [Epub ahead of print].
148. Rinkel GJ, Feigin VL, Algra A, van den Bergh WM, Vermeulen M, van Gijn J. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2005;(1):CD000277.
149. Chumnanvej S, Dunn IF, Kim DH. Three-day phenytoin prophylaxis is adequate after subarachnoid hemorrhage. Neurosurgery. 2007;60:99–102; discussion 102–3.
150. Bardach NS, Zhao S, Gress DR, Lawton MT, Johnston SC. Association between subarachnoid hemorrhage outcomes and number of cases treated at California hospitals. Stroke. 2002;33:1851–1856.
151. Berman MF, Solomon RA, Mayer SA, Johnston SC, Yung PP. Impact of hospital-related factors on outcome after treatment of cerebral aneurysms. Stroke. 2003;34:2200–2207.
152. Cross DT, Tirschwell DL, Clark MA, et al.. Mortality rates after subarachnoid hemorrhage: variations according to hospital case volume in 18 states. J Neurosurg. 2003;99:810–817.
153. Johnston SC. Effect of endovascular services and hospital volume on cerebral aneurysm treatment outcomes. Stroke. 2000;31:111–117.
154. Anxionnat R, Bracard S, Ducrocq X, et al.. Intracranial aneurysms: clinical value of 3D digital subtraction angiography in the therapeutic decision and endovascular treatment. Radiology. 2001;218:799–808.
155. Willinsky RA, Taylor SM, TerBrugge K, Farb RI, Tomlinson G, Montanera W. Neurologic complications of cerebral angiography: prospective analysis of 2,899 procedures and review of the literature. Radiology. 2003;227:522–528.
156. White PM, Teasdale EM, Wardlaw JM, Easton V. Intracranial aneurysms: CT angiography and MR angiography for detection prospective blinded comparison in a large patient cohort. Radiology. 2001;219:739–749.
157. White PM, Wardlaw JM, Easton V. Can noninvasive imaging accurately depict intracranial aneurysms? (A systematic review). Radiology. 2000;217:361–370.
158. Agid R, Lee SK, Willinsky RA, Farb RI, Terbrugge KG. Acute subarachnoid hemorrhage: using 64-slice multidetector CT angiography to "triage" patients' treatment. Neuroradiology. 2006;48:787–794.
159. Chappell ET, Moure FC, Good MC. Comparison of computed tomographic angiography with digital subtraction angiography in the diagnosis of cerebral aneurysms: a meta-analysis. Neurosurgery. 2003;52:624–631.
160. El Khaldi M, Pernter P, Ferro F, et al.. Detection of cerebral aneurysms in nontraumatic subarachnoid haemorrhage: role of multislice CT angiography in 130 consecutive patients. Radiol Med (Torino). 2007;112:123–137.
161. Boet R, Poon WS, Lam JM, Yu SC. The surgical treatment of intracranial aneurysms based on computer tomographic angiography alone–streamlining the acute mananagement of symptomatic aneurysms. Acta Neurochir (Wien). 2003;145:101–105; discussion 105.
162. Caruso R, Colonnese C, Elefante A, Innocenzi G, Raguso M, Gagliardi FM. Use of spiral computerized tomography angiography in patients with cerebral aneurysm (Our experience). J Neurosurg Sci. 2002;46:4–9; discussion 9.
163. Hoh BL, Cheung AC, Rabinov JD, Pryor JC, Carter BS, Ogilvy CS. Results of a prospective protocol of computed tomographic angiography in place of catheter angiography as the only diagnostic and pretreatment planning study for cerebral aneurysms by a combined neurovascular team. Neurosurgery. 2004;54:1329–1340; discussion 1340–2.
164. Pechlivanis I, Schmieder K, Scholz M, Konig M, Heuser L, Harders A. 3-Dimensional computed tomographic angiography for use of surgery planning in patients with intracranial aneurysms. Acta Neurochir (Wien). 2005;147:1045–1053; discussion 1053.
165. Westerlaan HE, van der Vliet AM, Hew JM, Metzemaekers JD, Mooij JJ, Oudkerk M. Magnetic resonance angiography in the selection of patients suitable for neurosurgical intervention of ruptured intracranial aneurysms. Neuroradiology. 2004;46:867–875.
166. Sato M, Nakano M, Sasanuma J, Asari J, Watanabe K. Preoperative cerebral aneurysm assessment by three-dimensional magnetic resonance angiography: feasibility of surgery without conventional catheter angiography. Neurosurgery. 2005;56:903–912.
167. Johnson MR, Good CD, Penny WD, Barnes PR, Scadding JW. Lesson of the week: playing the odds in clinical decision making: lessons from berry aneurysms undetected by magnetic resonance angiography. BMJ. 2001;322:1347–1349.
168. White PM, Wardlaw JM, Lindsay KW, Sloss S, Patel DK, Teasdale EM. The non-invasive detection of intracranial aneurysms: are neuroradiologists any better than other observers?. Eur Radiol. 2003;13:389–396.
169. Broderick J, Brott T, Duldner J, Tomsick T, Leach A. Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage. Stroke. 1994;25:1342–1347.
170. Roos YB, de Haan RJ, Beenen LF, Groen RJ, Albrecht KW, Vermeulen M. Complications and outcome in patients with aneurysmal subarachnoid haemorrhage: a prospective hospital based cohort study in the Netherlands. J Neurol Neurosurg Psychiatry. 2000;68:337–341.
171. Kassell NF, Torner JC. Aneurysmal rebleeding: a preliminary report from the Cooperative Aneurysm Study. Neurosurgery. 1983;13:479–481.
172. Naidech AM, Janjua N, Kreiter KT, et al.. Predictors and impact of aneurysm rebleeding after subarachnoid hemorrhage. Arch Neurol. 2005;62:410–416.
173. Rose J, Mayer SA. Optimizating blood pressure in neurological emergencies. Neurocrit Care. 2004;1:287–300.
174. Roos YB, Rinkel GJ, Vermeulen M, Algra A, van Gijn J. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2003;(2):CD001245.
175. Leipzig TJ, Redelman K, Horner TG. Reducing the risk of rebleeding before early aneurysm surgery: a possible role for antifibrinolytic therapy. J Neurosurg. 1997;86:220–225.
176. Hillman J, Fridriksson S, Nilsson O, Yu Z, Saveland H, Jakobsson KE. Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study. J Neurosurg. 2002;97:771–778.
177. Hasan D, Vermeulen M, Wijdicks EF, Hijdra A, van Gijn J. Management problems in acute hydrocephalus after subarachnoid hemorrhage. Stroke. 1989;20:747–753.
178. Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery. 1980;6:1–9.
179. Harrod CG, Bendok BR, Batjer HH. Prediction of cerebral vasospasm in patients presenting with aneurysmal subarachnoid hemorrhage: a review. Neurosurgery. 2005;56:633–654; discussion 633–54.
180. Rabinstein AA, Friedman JA, Weigand SD, et al.. Predictors of cerebral infarction in aneurysmal subarachnoid hemorrhage. Stroke. 2004;35:1862–1866.
181. Barker FG, Ogilvy CS. Efficacy of prophylactic nimodipine for delayed ischemic deficit after subarachnoid hemorrhage: a metaanalysis. J Neurosurg. 1996;84:405–414.
182. van den Bergh WM, Algra A, van Kooten F, et al.. Magnesium sulfate in aneurysmal subarachnoid hemorrhage: a randomized controlled trial. Stroke. 2005;36:1011–1015.
183. Sen J, Belli A, Albon H, Morgan L, Petzold A, Kitchen N. Triple-H therapy in the management of aneurysmal subarachnoid haemorrhage. Lancet Neurol. 2003;2:614–621.
184. Wijdicks EF, Kallmes DF, Manno EM, Fulgham JR, Piepgras DG. Subarachnoid hemorrhage: neurointensive care and aneurysm repair. Mayo Clin Proc. 2005;80:550–559.
185. Rinkel G, Feigin V, Algra A, Gijn J. Circulatory volume expansion therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2004(4):CD000483.
186. Vajkoczy P, Horn P, Bauhuf C, et al.. Effect of intra-arterial papaverine on regional cerebral blood flow in hemodynamically relevant cerebral vasospasm. Stroke. 2001;32:498–505.
187. Badjatia N, Topcuoglu MA, Pryor JC, et al.. Preliminary experience with intra-arterial nicardipine as a treatment for cerebral vasospasm. AJNR Am J Neuroradiol. 2004;25:819–826.
188. Biondi A, Ricciardi GK, Puybasset L, et al.. Intra-arterial nimodipine for the treatment of symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage: preliminary results. AJNR Am J Neuroradiol. 2004;25:1067–1076.
189. Feng L, Fitzsimmons BF, Young WL, et al.. Intraarterially administered verapamil as adjunct therapy for cerebral vasospasm: safety and 2-year experience. AJNR Am J Neuroradiol. 2002;23:1284–1290.
190. Higashida RT, Halbach VV, Cahan LD, et al.. Transluminal angioplasty for treatment of intracranial arterial vasospasm. J Neurosurg. 1989;71(5 Pt 1):648–653.
191. David CA, Vishteh AG, Spetzler RF, Lemole M, Lawton MT, Partovi S. Late angiographic follow-up review of surgically treated aneurysms. J Neurosurg. 1999;91:396–401.
192. Malek AM, Halbach VV, Phatouros CC, et al.. Balloon-assist technique for endovascular coil embolization of geometrically difficult intracranial aneurysms. Neurosurgery. 2000;46:1397–1406; discussion 1406–7.
193. Fiorella D, Albuquerque FC, Han P, McDougall CG. Preliminary experience using the Neuroform stent for the treatment of cerebral aneurysms. Neurosurgery. 2004;54:6–16; discussion 16–7.
194. Kwon OK, Kim SH, Kwon BJ, et al.. Endovascular treatment of wide-necked aneurysms by using two microcatheters: techniques and outcomes in 25 patients. AJNR Am J Neuroradiol. 2005;26:894–900.
195. Raymond J, Guilbert F, Weill A, et al.. Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils. Stroke. 2003;34:1398–1403.
196. Molyneux A, Kerr R, Stratton I, et al.. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet. 2002;360:1267–1274.
197. Molyneux AJ, Kerr RS, Yu LM, 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.
198. Helland CA, Krakenes J, Moen G, Wester K. A population-based study of neurosurgical and endovascular treatment of ruptured, intracranial aneurysms in a small neurosurgical unit. Neurosurgery. 2006;59:1168–1175; discussion 1175–6.
