The clinical presentation of aSAH is very typical. About 80% of patients who provide a medical history describe the symptoms as “the most severe headache ever”, while another 20% have an aura of headache attack. SAH can occur at any time, and can be triggered by factors such as heavy labor or exercise. In addition to headache, it may be accompanied by nausea, vomiting, neck stiffness, transient loss of consciousness, or focal neurological deficits (including cerebral nerve palsy).
In a retrospective study of 109 patients diagnosed with SAH, Fontanarosa found that 74% of them had headache, 77% had nausea or vomiting, 53% had loss of consciousness, and 35% had cervical dystonia. Twelve percent of these patients died before receiving treatment. In addition to the typical clinical manifestations, there are other symptoms of SAH. Because headache manifestations vary from patient to patient, misdiagnosis or delayed diagnosis often occurs.
Before 1985, the rate of misdiagnosis of SAH used to be 64%, but recently it has decreased to about 12%. In patients with little or no neurological symptoms, the 1-year mortality and disability rates of misdiagnosed patients are 4 times higher than those of other patients [21 ]. The most common reason for misdiagnosis is that the patient did not receive a CT scan of the head. The patient’s history may show a small amount of bleeding before the hemorrhage occurred, which is called “aura bleeding”.
Most aura hemorrhage headaches are not severe but last for several days, most occurring within 2 to 8 weeks before the hemorrhage [ 1982199 ]. Nausea and vomiting may also be present without signs of meningeal irritation. In three studies involving 1752 patients, 340 (15%-37%, mean 20%) had a history of sudden onset of headache before the onset of severe symptoms. Of course, we cannot overemphasize the importance of “aura hemorrhage”. SAH patients account for only 1% of all headache emergencies. More than 20% of patients with SAH have epilepsy, usually within 24 hours of bleeding, and most often in patients with combined cerebral hemorrhage, hypertension, and middle and anterior communicating cerebral aneurysms.
The basic diagnostic method for SAH is CT scan of the head, and its detection rate is related to the clinical classification of the patient and the time to hemorrhage. The detection rate of CT is as high as 98%-100% within 12 hours after SAH; it decreases to 93% after 24 hours; while the detection rate is only 57%-85% at 6 days after bleeding. Since the detection rate of CT could not be ensured to 100%, diagnostic lumbar puncture was performed when the CT result was negative.
Proper puncture technique, proper sample testing, and correct analysis of cerebrospinal fluid composition are essential to confirm the diagnosis. The key points of examination are: the ratio of red and white blood cells in the cerebrospinal fluid, the presence of yellow staining, the presence of bilirubin, and the timing of the lumbar puncture, etc. Guidelines for the diagnosis of SAH by examination of the cerebrospinal fluid have been published. The prognosis is generally good in patients who present with sudden severe headache and whose aura hemorrhage is ruled out by CT and cerebrospinal fluid examination. We recommend that patients with negative tests still require repeat testing, management of headache symptoms, and outpatient follow-up.
MR I can also be used to diagnose SAH, and the use of techniques such as proton density-weighted imaging and fluid-attenuated inversion recovery sequences has significantly increased the detection rate of MR I in the acute phase of SAH. However, there are still many limitations, such as the immediacy of MRI, sensitivity to motion artifacts, patient compliance, and the long and costly time required for the examination.
In conclusion, these factors have limited the use of MRI as a routine test in the acute phase of SAH. MR I and MRA are more suitable for patients with negative head CT or angiography and inconclusive lumbar puncture results. The use of MRA has also increased significantly in the last decade in the diagnosis of SAH, but it still cannot replace cerebral angiography in determining the nature and location of aneurysms. Not only are the limitations of MR I examination present in MRA, but other factors, such as the size of the aneurysm, imaging sequence, and image processing, can affect the results. The sensitivity of 32dimensional time2of2flight MRA imaging for aneurysms ranges from 55% to 93% and is highly correlated with the size of the aneurysm. When the aneurysm is ≥5 mm, the sensitivity of MRA is as high as 85%-100%; but when the aneurysm is <5 mm, the sensitivity decreases to 56%.
MRA also has limitations in examining the aneurysm neck and its relationship to the vessel. MRA can also be used as a screening tool for patients without SAH.
CTA is faster and less invasive than angiography and has been shown to be as sensitive as angiography for larger aneurysms. The CTA images include the bifurcation of the middle cerebral artery and the foramen ovale. The sensitivity of CTA for aneurysms is 77% to 100%, and the specificity is 79% to 100%.
The sensitivity and specificity depend on the location and size of the aneurysm, the experience of the radiologist, and the reconstruction quality of the image. When the aneurysm is ≥5 mm, the sensitivity of CTA is 95%-100%; if the aneurysm is <5 mm, the sensitivity of CTA decreases to 64%-83%. Vascular tortuosity also reduces the specificity of CTA, especially in the bifurcation of the middle cerebral artery, the anterior communicating artery and the inferior posterior cerebellar artery, which can be easily mistaken for aneurysms. The more experienced the operator, the better the accuracy of CTA in detecting aneurysms. Velthuis et al [232] also found no difference between CTA and angiography in 80% to 83% of patients with aneurysms detected by CTA after surgery. In patients who underwent CTA followed by angiography, no new information was found in 74% of them.
In the above study, the neurosurgeon performed the procedure based on CTA alone, which may have reduced the risk of waiting for angiography, but this was not evaluated in the data and conclusions. CTA can also be used to supplement angiographic findings.
CTA can detect severe vasospasm but is not as accurate in mild to moderate vasospasm [234], and is particularly useful in critically ill patients because it is fast and widely available. The disadvantages of CTA include the need for contrast injections, the impact of bony artificial materials on imaging quality, and the inability to examine small distal vessels; moreover, metallic foreign bodies can interfere with CTA after embolization or clamping of aneurysms. As the use of CTA becomes more common, it has become an important supplement to angiography and may one day replace it.
At present, selective angiography is still the gold standard for the diagnosis of aSAH. It is worth noting that 20%-25% of SAH patients have not found the cause of bleeding after angiography, and about 1 week later, reangiography can detect 1%-2% of patients with previously undetected aneurysms. However, it is controversial whether such a low re-detection rate warrants a second imaging.
Summary and recommendations:
① SAH is a clinical emergency that is often misdiagnosed. If a patient has a sudden onset of severe headache, SAH should be highly suspected (Class I, Level B evidence).
Patients suspected of SAH should undergo CT examination (Class I, Level B evidence), and when the CT examination result is negative, lumbar puncture should be performed (Class I, Level B evidence).
For patients with confirmed SAH, selective cerebral angiography should be performed to clarify the presence or absence of aneurysm and its anatomical features (Class I, Level B evidence).
④If cerebral angiography cannot be performed, MRA and CTA should be considered (Class IIb Level B evidence).
6.Emergency evaluation and preoperative treatment of SAH patients
The hyperacute management of SAH has not received enough attention because at least 2/3 of patients are treated by emergency personnel in the early stages. The model of rapid assessment of patients in the acute phase of ischemic stroke followed by thrombolysis has been successful and should be replicated. Although not all patients with SAH have focal neurological deficits at the time of emergency, EMS personnel should have a high suspicion of SAH if the patient has more than one symptom and sign, including headache, varying degrees of consciousness, or vomiting, and should receive continuing education so that they are fully aware of the importance of neurological assessment when patients present with varying degrees of consciousness. Hospital emergency rooms should be notified in advance of rapid patient transport to avoid unnecessary delays.
Patients with SAH should be evaluated first to maintain airway patency, respiratory and circulatory function. Although airway obstruction is rare in patients with SAH, patients with severe neurological deficits need to be monitored for airway patency. If the patient becomes unconscious and has difficulty breathing, tracheal intubation should be performed, and rapid intubation should be used. At the same time, special attention should be paid to maintaining the patient’s oxygen level, monitoring the heart, and avoiding blood pressure fluctuations. After tracheal intubation, a nasal or oral gastric tube should be placed to avoid inadvertent aspiration. Adjust the appropriate oxygen concentration, avoid hyperventilation, and review blood gases regularly. A detailed physical examination and medical history should be taken, and special attention should be paid to the risk factors of SAH. For young patients or those with a history of drug abuse, it is important to test
whether they are intoxicated. On admission, it is important to record risk factors that may affect the patient’s prognosis, such as age, history of hypertension, time between onset and presentation, and blood pressure at the time of presentation.
There are several assessment scales available for evaluating patients with SAH, including the Hunt2Hess scale, Fisher scale, Glasgow coma score, and WFNS scale. In fact, each scale has its limitations. Most of these scales are from retrospective studies and do not assess differences between evaluators. Although the choice of scale is controversial, we recommend that first responders choose one scale to assess patients with SAH and document it. If a specialist is not available at the hospital to which the patient is transported, EMS personnel should consider transferring the patient to another hospital.
Summary and recommendations:
(1) Neurological function scores of patients with SAH using recognized scales are useful in determining the prognosis of patients (Class IIa, Level B evidence).
(2) At present, there are no criteria for the evaluation of patients with headache and other symptoms in the emergency room of each hospital, and it is recommended that they should be established whenever possible (Class IIa Level C evidence).
Measures to prevent rebleeding after SAH
Bed rest is an important measure to prevent rebleeding in patients with SAH. Although bed rest alone does not reduce the incidence of rebleeding in modern medicine, it is part of the treatment to prevent rebleeding [ 138, 144, 2402244 ]. There are no rigorous controlled studies to confirm the relationship between blood pressure control and rebleeding in the acute phase of SAH. A retrospective study of factors influencing rebleeding showed that the incidence of rebleeding did decrease after treatment with antihypertensive drugs, although patients’ blood pressure remained high.
Moreover, the incidence of rebleeding was more correlated with blood pressure fluctuations than with the absolute value of blood pressure; it has also been reported that patients with SAH had elevated blood pressure before rebleeding. In a retrospective analysis of 179 patients with SAH admitted within 24 h of bleeding, 17% had rebleeding with a systolic blood pressure >150 mm Hg. The cause of this phenomenon is unclear, but it can be inferred that a higher blood pressure than that of the first bleeding indicates that the patient is likely to rebleed. In one study, the incidence of rebleeding in emergency vehicles and hospitals was 13.6%, with a peak within 2 h of the first bleed, and was more common in patients with systolic blood pressure > 160 mm Hg.
Another large retrospective study reported a rebleeding rate of 6. 9% after hospital admission, but this was not related to the patient’s blood pressure. Differences in the duration of observation and the use of antihypertensive medications may account for this difference. When the patient’s blood pressure is elevated, a short-acting, safe antihypertensive drug should be continuously infused intravenously. Therefore, antihypertensive drugs such as nicardipine, labetalol, and esmolol are preferred. If the patient has acute neurological symptoms, it is best not to choose sodium nitroprusside, because it has the adverse effect of increasing intracranial pressure and may cause poisoning by prolonged infusion.
As early as 1967, researchers began to study the role of antifibrinolytic therapy in preventing rebleeding. Adams et al. reviewed three studies (two randomized studies and one prospective phase IV study) related to antifibrinolytic therapy and found a significant reduction in rebleeding rates in the treatment group compared with the control group. However, nearly 1/3 of the patients in the treatment group had worse disease at 14 d than at the time of admission. A multicenter, randomized, double-blind, placebo-controlled trial of tranexamic acid showed a >60% reduction in rebleeding rates in the treatment group, but the prognosis was not improved by the reduction in rebleeding rates because many patients experienced cerebral ischemia.
In a non-randomized controlled trial by Kassell et al, a similar conclusion was reached, with a 40% reduction in rebleeding rates in patients treated with tranexamic acid, although 43% of patients had an ischemic stroke. In another double-blind placebo-controlled trial of tranexamic acid [249 ], there was no difference in rebleeding rates between the trial and control groups, and the incidence of ischemic stroke was still higher in the trial group, but given the small sample size of the trial, this finding is not sufficiently reliable.
In other retrospective studies, the effect of aminocaproic acid (36 g/d) or tranexamic acid (2-6 g/d) was consistent regardless of the duration of administration. In the early treatment of SAH, the combination of antifibrinolytic therapy with prophylactic antivascular spasm therapy can reduce the rebleeding rate and prevent the occurrence of ischemic stroke. Another prospective randomized study on the efficacy of antifibrinolytic therapy showed that the administration of antifibrinolytic drugs immediately after the diagnosis of SAH was effective in reducing early rebleeding rates and adverse outcomes.
Summary and recommendations:
①Patients’ blood pressure must be monitored and controlled to prevent stroke, hypertension-related rebleeding, and to maintain cerebral perfusion pressure (Class I, Level B evidence).
(2) Bed rest alone does not reduce the incidence of rebleeding after SAH, but it is part of the overall treatment (Class IIb, Level B evidence).
Although previous studies have largely rejected the efficacy of antifibrinolytic therapy in patients with SAH, there is recent evidence that antifibrinolytic therapy given immediately after the onset of SAH and early management of aneurysms is effective in preventing hypovolemia and treating vasospasm (Class IIb Level B evidence). However, this conclusion needs to be studied in more depth. In addition, antifibrinolytic therapy should be considered to prevent rebleeding when the patient is at low risk for vasospasm and/or when surgery needs to be postponed (Class IIb Level B evidence).
Surgical or endovascular treatment of ruptured aneurysms
In 1991, Guglielmi et al [ 252 ] invented the electrolytic detachable platinum spring coil (GDC) for embolization of aneurysms. The spring coil was delivered to the aneurysm lumen by means of a micro-guide wire and a micro-catheter, and then dislodged by electrolysis. The spring coil not only fills the aneurysm, but also induces thrombosis within the aneurysm, thereby isolating the aneurysm wall from blood flow. With the accumulation of clinicians’ experience, the improvement of spring coil design, and the development of complementary technologies, endovascular treatment of aneurysms has become more widely used, and its efficacy is also related to the level of treatment in hospitals. The rate of endovascular treatment varies greatly from hospital to hospital. Some hospitals consider aneurysm clamping only when embolization is not feasible, while others use endovascular treatment in only 1% of patients with aneurysms, or set special angiographic criteria. A Meta-analysis examining the risk of spring-ring embolization reviewed the literature published from January 1990 to March 1997 and included 1256 patients, of whom 2. 4% had intraoperative aneurysm rupture, 8. 5% had ischemic adverse events, and 3. 7% of these patients had permanent complications.
The prognosis of SAH is mainly related to the severity of the initial bleeding, but also to intraoperative adverse events. The adverse consequences of endovascular treatment and craniotomy are more pronounced in the treatment of unruptured aneurysms. In the recently published International Study of Unruptured Aneurysms (ISAT), the rates of death and disability at 30 d after embolization were 2.0% and 7.4%, respectively. Although no intraoperative adverse events were reported in the recent ISAT study, the mortality and disability rates at 2 months after embolization were 2514%, including, of course, the damage caused by the bleeding itself. The effectiveness of treatment of intracranial aneurysms depends on two main factors: the rate of rebleeding and the rate of recurrence of the aneurysm by imaging.
Several case-group studies have summarized the rate of rebleeding after SAH embolization, and seven of these reported cases included all locations of the aneurysm, thus providing enough information to study its rebleeding rate [2592265 ]. Combining this literature leads to the broad conclusion that the rebleeding rate after aneurysm embolization is approximately 0. 9% per year. In a recent study of 431 patients with ruptured aneurysms treated with embolization, the early rebleeding rate was 114% and the mortality rate for rebleeding was 100%, including 2 patients whose aneurysms had reached complete occlusion by imaging. The rebleeding rate at 1 year after embolization was approximately 2.9%. More recently, BostonScientific sponsored a study by nine high-case volume hospitals in the western United States that followed patients treated with spring-ring embolization in 1996-1998 by telephone and questionnaire to obtain long-term rebleeding rates after embolization. Although follow-up rates were not available, the study noted that rebleeding occurred within 12 months of treatment and that rebleeding rates were higher after embolization than after surgical clamping.
Four groups of data were studied on rebleeding after embolization of ruptured aneurysms in the posterior circulation:
(i) A follow-up study of 34 ruptured distal basilar artery aneurysms showed that only 1 aneurysm without complete occlusion ruptured in 74. 8 person-years, with a rebleeding rate of 113% per year.
(ii) A 1. 1-year follow-up study of 61 patients concluded that the annual re-rupture rate of aneurysms after embolization was 219%.
(iii) A study of 104 patients showed an annual rebleeding rate of 019%.
(iv) A study of 23 patients found no rebleeding during 24 person-years of follow-up. Taken together, the annual rebleeding rate after embolization of ruptured posterior circulation aneurysms can be estimated to be 1. 4%.
Several cohort studies have addressed the issue of rebleeding after spring-ring embolization, but have neither provided the duration of follow-up nor distinguished whether the treated aneurysm ruptured, thus preventing us from calculating the rate of rebleeding after aneurysm embolization. Nevertheless, the above studies provide risk factors for reruptive bleeding after aneurysm embolization, of which size, shape, and history of bleeding are the most important. In a cohort study of ruptured aneurysms ≥2 cm in diameter, one case of rebleeding was found during 36 person-years of follow-up, with an annual rebleeding rate of 2.7%.
Another consecutive case study, which included both ruptured and unruptured aneurysms, showed that the annual bleeding rate after aneurysm embolization was 1. 8% and that rebleeding was strongly correlated with aneurysm size, with 33% of large aneurysms and 4% of large aneurysms experiencing rebleeding at a mean follow-up of 3. 5 years, while small aneurysms did not rebleed. Another group of cases with 141 person-years of follow-up reported an annual re-rupture rate of 1. 4% for aneurysms, and the degree of occlusion was also significantly correlated with the re-bleeding rate.
Case reports and case cohort studies have confirmed that aneurysms that have been completely occluded after surgery or endovascular treatment still have the potential to rebleed. However, most rebleeding occurs in patients with incomplete aneurysm occlusion on post-treatment imaging.
However, most rebleeding occurs in patients with incomplete aneurysm occlusion on post-treatment imaging. In a group of 178 patients with incomplete aneurysm occlusion after endovascular treatment, the regrowth rate was as high as 49%. The majority of intracranial aneurysms do not achieve complete occlusion with one treatment. A Meta-analysis showed that only 54% of aneurysms were completely occluded, whereas 88% of aneurysms with occlusion rates >90% were completely occluded.
In the largest case cohort study in North America, Murayama et al. followed 818 patients (916 aneurysms) embolized over 11 years and found that only 55% of the aneurysms achieved complete occlusion. The size and shape of the aneurysm were the most important reasons for incomplete occlusion and recurrence. The study excluded patients treated within the first 5 years, when medical technology was still at the beginning of the learning curve, and focused on 558 patients (665 aneurysms) treated over the last 6 years.
The results showed that the incomplete embolization rate of small aneurysms with narrow necks (≤4 mm) (aneurysms 4-10 mm in diameter) was 25.5% and the recurrence rate was 21%, while the recurrence rate of complete embolization was only 1.1%; for small aneurysms with wide necks (>4 mm), the incomplete embolization rate was 59% and the recurrence rate was 29.4%, while the recurrence rate of complete embolization was 7.5%; for large aneurysms with aneurysms 11-25 mm in diameter, the incomplete embolization rate was 56%, while the recurrence rate of complete embolization was 7.5%. In large aneurysms with a diameter of 11-25 mm, the rate of incomplete embolization is 56%, the recurrence rate is 44%, and the recurrence rate of complete embolization is 30%; in giant aneurysms with a diameter of >25 mm, the rate of incomplete embolization is 63%, the recurrence rate is 60%, and the recurrence rate of complete embolization is 42%.
Even in the most experienced treatment centers, incomplete embolization of aneurysms and the occurrence of rebleeding have reduced their efficacy, despite a reduction in embolization-related complications. However, clinical outcome depends not only on the embolization itself, as most incompletely embolized aneurysms do not rebleed. Therefore, the effectiveness of treatment can only be determined after long-term clinical follow-up and imaging. A recent paper suggests that enhanced gadolinium MRA can be used as an alternative to imaging for follow-up. Follow-up with imaging can detect recurrent aneurysms and manage them before they become symptomatic. Risk, cost, and the inconvenience of multiple imaging reviews should be considered when evaluating the efficacy of endovascular therapy. Although the degree of aneurysm occlusion is not the only factor affecting rebleeding, complete occlusion of the aneurysm remains a common goal of endovascular and surgical treatment.