Unruptured Intracranial Aneurysms: Clinical Characteristics and Management Considerations

Approximately 85% of cases of saccular aneurysms are lesions acquired within the anterior circulation, characterized by a protrusion of the arterial wall, due to its thinning.

They commonly occur at arterial bifurcations , such as the junction of the anterior communicating artery with the anterior cerebral artery, the junction of the posterior communicating artery with the internal carotid artery (ICA), and the bifurcation of the middle cerebral artery.

Because posterior circulation aneurysms are less common, they are more likely to have worse outcomes (cognitive disability and sudden death). Unruptured intracranial aneurysms (UA) ≤7 mm are asymptomatic and detected incidentally on neuroimaging, thanks to advances in non-invasive methods such as computed tomography angiography (CTA) and magnetic resonance angiography (ARM).

Subarachnoid hemorrhage ( SAH) is one of the presentation forms of IAs, when they rupture. The natural history of NRAs remains poorly understood, because the possibility of treatment prevents them from reaching the end of the trial. The presence of multiple aneurysms and a family history of aneurysm suggests a genetic basis.

> Pathogenesis

The most common AINRs are the saccular type, although the fusiform type is not rare.

Normal intracranial arteries are composed of the lamina intima (basement membrane and endothelial cells), the media (smooth muscle cells and elastin fibers), and the adventitia, which includes collagen, essential for the structural integrity of the vessels. Hemodynamic stress triggers a process of localized inflammatory infiltration, with weakening of the vessel wall and aneurysm formation.

Degeneration of the internal elastic lamina, which causes separation of the lamina intima and media, is a key structural process in the development of IAs. Metalloproteases also intervene, the inhibition of which hinders aneurysmal progression.

On the other hand, it is highlighted that ruptured aneurysms show greater immunohistochemical staining of cyclooxygenase 2 and microsomal prostaglandin E2 synthase, while in vivo studies have shown a reduction in experimental cerebral aneurysms with the use of anti-inflammatory medications. Thus, studies on the action of aspirin showed a protective role in the development and progression of ANNR, through the attenuation of inflammation, since it inhibits cyclooxygenase 2 and microsomal prostaglandin E2 synthase.

Macrophages may be associated with aneurysmal rupture. In AINR, M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages are present. S has postulated the existence of an imbalance in favor of the action of M1 cells, which favors the rupture of AIs. As the stages of degeneration of the saccular aneurysm walls progress, the risk of death increases.

> Epidemiology and risk factors

The prevalence of AINR is approximately 3.2% of the general population, with a mean age of 50 years; 20-30% of patients have multiple aneurysms.

Prospective autopsies and angiographic studies have shown that 3.6% to 6% of the population harbors an IA. Almost 50% to 80% of AINRs do not break down. The annual rate of de novo aneurysm formation is 0.3% to 1.8%, while the annual incidence of IA growth is 1.51% to 22.7%.

It is likely that the female predominance, which reaches 2:1 after age 50, is related to collagen reduction due to postmenopausal hypoestrogenemia. It is likely that there is a genetic predisposition to the formation of IAs.

Although AINRs are usually acquired sporadic lesions, familial forms have been linked to arteriovenous malformations, coarctation of the aorta, fibromuscular dysplasia, Marfan syndrome, Ehlers-Danlos syndrome type IV, autosomal dominant polycystic kidney disease, familial aldosteronism type 1, sickle cell anemia and Moyamoya.

Family history is a higher risk factor for developing AINR. Patients with 1 affected family member have a 4% risk of developing IA. Those who have ≥2 affected first-degree relatives have a risk of 8% to 10%. The location of aneurysms can also be similar within families and aneurysm rupture tends to occur in the same decade of siblings’ lives. Compared to sporadic AIs, familial AINRs tend to rupture at a younger age and with smaller sizes.

Hypertension, smoking, and alcohol consumption increase the risk of developing AINR.

Hypertension, which is prevalent in patients with AINR, is a significant risk factor for future SAH. There are no current studies showing that blood pressure control prevents the development of AI.

However, a Finnish study found indirect evidence that antihypertensives were used more frequently in the AINR group, while untreated hypertension was more common in patients with ruptured AIs. Another study found that controlling blood pressure decreases the risk of aneurysm rupture. However, in another trial, blood pressure control did not affect the development of AI.

It has been proven that the greater the number of cigarettes smoked per day, the greater the risk of developing AINR. In individuals with α1-antitrypsin deficiency, smoking increases the predisposition to form AI by further reducing the level of α1-antitrypsin. There appears to be a synergism between risk factors such as high blood pressure and smoking, which increases the risk of developing AINR more than expected.

AINRs are usually asymptomatic and discovered incidentally on neuroimaging.

Symptomatic NRIAs may manifest vaguely or with nonspecific symptoms, such as headache, dizziness, and visual disturbances. Large AINRs can compress adjacent brain structures, such that ICA aneurysms can cause visual field defects or hemiparesis, while aneurysms of the basilar or posterior communicating arteries can cause oculomotor nerve palsies. This paralysis can manifest as eyelid ptosis.

Carotid cavernous aneurysms may present pupillary dilation, due to loss of pupillary sphincter function, strabismus, or facial pain. It can also be expressed by ischemic symptoms, due to an embolus generated in a carotid aneurysm.

In a retrospective study from a neurological center, 51% of AINR were asymptomatic, 17% manifested with acute symptoms (ischemia, 37%; headache, 37%; seizures, 15.7%, cranial neuropathy, 10.5 %) and, 32%, chronic symptoms due to a mass effect (headache, 51%; visual deficit, 29%; weakness, 11%; and facial pain, 9%).

AINRs can be diagnosed by MRA, CTA, and catheter angiography. Each modality has advantages and disadvantages, in various stages of the evaluation and management of IAs. Once the diagnosis of AINR is made, the anatomical details of the aneurysm are noted to classify it and decide its management.

The initial study to detect the aneurysm is usually CTA with intravenous contrast, which provides three-dimensional images that help better visualize the cerebral vessels.

Its sensitivity is 77% to 97%, and specificity is 87% to 100%. For AI <3 mm, sensitivity decreases between 40% and 91%.

Multidetector CTA has greater sensitivity and specificity (>97% for both) and better detection of aneurysms ≥4 mm compared to single-detector CTA. Iodinated contrast agents are used for CTA, which carry the risk of anaphylaxis and are contraindicated in patients with renal failure. In patients with coiled aneurysms, CTA has significant coil artifacts and generally does not show the anatomy of the aneurysm in the same slice as the artifacts.

On the other hand, the presence of multiple clips may prevent the neck of the aneurysm and adjacent vessels from being seen. For aneurysms ≥3 mm, the sensitivity of MRA is 74% to 98% and specificity is 100%. Sensitivity for aneurysms <3 mm decreases to 40%.

The preferred imaging modality for monitoring spiral IAs is contrast-enhanced MRA.

It is used in patients who are allergic to iodinated contrast agents, or to avoid radiation exposure. It is more difficult to obtain in critically ill or anxious patients, due to the duration of the study. Currently, there are new contrast agents that make it possible to dispense with gadolinium, which causes nephrogenic systemic fibrosis, in patients with end-stage renal disease.

Catheter angiography is the "gold standard" for the study of IAs. It allows detailed evaluation of the aneurysm and adjacent vessels, and has high sensitivity for detecting aneurysms <3 mm and visualizing small perforating vessels.

Three-dimensional angiography provides even more detail of the IA than dimensional planar imaging. It is often used when there is a high clinical suspicion of AI and the images are normal. Compared with THA, MRA is more expensive and carries procedural risks, neurological complications (1.0%-2.5%), femoral artery injury (0.05%-0.55%), hematoma inguinal (6.9%-10.7%) and contrast-induced nephropathy (1%-2%).

These factors can be divided into patient-specific (female, hypertension, smoking) and aneurysm-specific (located in the posterior circulation, shape, large size). Aneurysm growth tends to occur more with larger aneurysms. AINRs are more likely to experience inconsistent, non-linear growth.

Aneurysms of 5 to 10 mm are at greatest risk for growth.

Aneurysms <8 mm grow 12 times larger than 12 mm aneurysms, while those in the ICA and basilar artery tend to grow larger than those located in other areas. The presence of multiple aneurysms is also associated with aneurysmal growth. Likewise, IAs are likely to grow and rupture when they coexist with intracranial arteriovenous malformations.

> Risk of rupture and natural history

Although the natural history of AINR has been well studied, it is still not completely known. So far, size and location are known to be associated with a higher risk of rupture. Data from natural history research studies are difficult to obtain because, once a diagnosis is made, most patients undergo therapeutic interventions.

The risk of rupture for growing aneurysms (recent growth) is 3.1% compared to 0.1% for stable AIs. For example, a ruptured 8 mm aneurysm may have undergone multiple growth episodes in the past, followed by stability for a long period. On the other hand, the risk of rupture of AINRs of 3 mm or less is considerably low, but not zero.

The risk increases in patients with AINR >7 mm, located in the anterior or posterior part of the communicating artery, patients <50 years old, hypertensive, with multiple aneurysms and 1 secondary sac. A natural history study reported that patients with aneurysms ≥3 mm have an annual rupture rate of 0.95%.

However, a higher risk of rupture has also been found in patients >60 years of age, if there is Finnish or Japanese ancestry, size >5 mm (or smaller, according to another study) and if the aneurysm is symptomatic. The role of racial differences in the natural history of AINR is unclear.

Individuals with a history of (SAH-A) are also at increased risk of repeat aneurysmal rupture. The PHASES score (population, hypertension, age, aneurysm size, earliest HSAA from other aneurysm, aneurysm site) is used to predict the risk of aneurysm rupture at 5 years. It takes into account the patient’s characteristics and risk factors. The role of antiplatelets and anticoagulants in NRSA is still a topic of debate.

One study reported that patients taking long-term aspirin have a lower risk of rupture, while dipyridamole and new aspirin use may be associated with SAH.

Aspirin has been found to be protective against aneurysmal rupture and the bleeding rate was lower in aspirin-treated patients (28%) than in untreated patients (40%), with no worsening of outcomes after AAHS. On the contrary, anticoagulants have been associated with poor outcome of SAH, without increasing the risk of aneurysm rupture.

The optimal management of AINRs is controversial, because their natural history is not completely known, because technological advances allow treatment once the diagnosis is obtained.

Therefore, all patients with AINR should be counseled about the importance of blood pressure control and smoking cessation. The management of NRAs must be individualized and, before deciding, the risk of rupture must be compared with the risk of the treatment. There are scoring systems for this evaluation.

> Screening

Screening for NRSA is usually reserved for high-risk patients, such as those with 2 first-degree relatives with a history of intracranial aneurysm, autosomal dominant polycystic kidney disease, coarctation of the aorta, and a history of SAH. In patients with only 1 affected family member, the decision depends on each case.

Patients with a history of new-onset headache also deserve special attention. After detection of an AINR, follow-up should be done after 6 to 12 months. If there are no changes in the images, they will be repeated for 2-3 years and then every 2-5 years.

Small, newly formed aneurysms are at greater risk for growth and rupture. If follow-up imaging shows aneurysmal enlargement, treatment and long-term follow-up should be considered.

Changes in headache characteristics warrant follow-up with repeated neuroimaging.

Regarding imaging follow-up of AINR ≤3 mm, it has not yet been determined, but it is recommended that it be performed every 5 years.

> Selection of patients for the intervention

As most patients remain asymptomatic for long periods, their natural history is not completely known, making it difficult to decide whether to follow conservative management (risk of rupture) or therapeutic management (successful but may have complications, termination of employment, confinement, death). Symptomatic IAs of all sizes justify endovascular treatment unless there is a high risk of the procedure or a low life expectancy.

When the aneurysm is complicated, other surgical procedures (eg, clipping, endovascular coiling) are used for ligation or occlusion to avoid embolizations. While these techniques are aimed at treating the aneurysm sac, for small, distal IAs, flow diverting devices are used. These devices are used for giant, wide-necked AIs, which are placed inside the parent artery, bypassing the neck, to divert blood away from the aneurysm sac; The result is thrombosis of the aneurysm but with continuity of arterial flow towards the part distal to the aneurysm.

Age is important when deciding the management of AINR, since in older patients morbidity and mortality are higher with both procedures. The location of the IA is also important, especially cavernous aneurysms of the ICA. For this type of IA, follow-up is usually conservative, because they are extradural and do not give rise to SAH. However, symptomatic cavernous aneurysms can cause cranial neuropathy and require treatment.

Intradural aneurysms can cause SAH and are best differentiated from extradural lesions on coronal images. Symptomatic intradural aneurysms of any size warrant treatment unless patients are at high procedural risk or limited life expectancy.

Most symptomatic cases can be treated endovascularly . Larger aneurysms with irregularities or a secondary sac are at higher risk of rupture and deserve consideration for treatment. A consensus suggests that although conservative treatment of AINR <7 mm is common, those measuring 7 to 12 mm usually undergo endovascular treatment.

Patients with a history of SAH-A were usually subjected to therapeutic intervention, but currently, the PHASES score allows IAs to be classified more precisely, allowing more appropriate decisions to be made. One study reported a pooled complication risk of endovascular therapy of 4.96% and a case fatality rate of 0.30%.

Factors associated with complications, reported in various studies, were: female sex, diabetes, hyperlipidemia, heart disease, wide-neck or posterior circulation IA, stent-assisted coiling and stenting, coagulopathy, use of antiplatelets, congestive heart failure , calcification of the aneurysm.

> Microsurgical clipping

Microsurgical clipping is the preferred treatment for AIs.

It is performed through an open craniotomy, which allows direct access to the neck of the aneurysm and the adjacent branches (which are clamped with clips), to be excluded from circulation. This vascular sacrifice can be evaluated preoperatively, using a balloon occlusion angiographic test, to estimate the risk of cerebrovascular accident (CVA) and evaluate the integrity of blood flow that will result postoperatively. When this test is not tolerated by the patient, clipping is completed with a flow diversion procedure. For this, flow diverting devices are used.

Microsurgical clipping is especially used in young patients with low surgical risk; AI of the anterior circulation, especially in those located superficially; small size (<10 mm). It has been proven that this treatment achieves circulatory exclusion of the aneurysm in 90% of operated patients. Regarding adverse effects on cognition, the results of the studies are discordant.

After surgery, poor outcomes were associated with: age > 50 years, aneurysm size (larger size, worse outcome) and location (higher risk of poor outcomes in posterior circulation IA), history of stroke, AINR, and SAH. , presence of symptoms (new onset of oculomotor nerve palsy and impending rupture).

Risks of microsurgical clipping include stroke (6.7%-10%) and hemorrhagic complications (2.4%-4.1%), incomplete aneurysm obliteration (5%) and recurrence (1.5%), infection, and seizures (0.1% for status epilepticus and 2% for any seizure). The best results correlate with high experience in the procedure (more than 20 cases vs. less than 4 cases/year).

> Endovascular treatment.

Treatment of AINRs has become increasingly common compared to open surgery. Microsurgical clipping and endovascular coiling have been proven to have very good results for both ruptured IAs and NRIAs. Currently, most IAs are treated endovascularly. Patients with IA in the anterior circulation and those <10 mm are excellent candidates for endovascular treatment.

Endovascular repair involves the endovascular introduction of a platinum coil, which is coiled into the aneurysm sac, through a microcatheter, to promote aneurysmal thrombosis, thereby. its occlusion and isolation from circulation.

If the patient does not tolerate the occlusion test, the procedure is completed with flow diversion, using a device that diverts arterial flow, bypassing the aneurysm. For large-neck IAs, there are additional techniques, such as balloon-assisted clipping or stent-assisted clipping. Prior to treatment, antiplatelet therapy should be indicated for 3-6 months.

Flow interruption is the newest intrasaccular technique for wide-necked aneurysms, using a Woven EndoBridge (WEB) device placed within the aneurysm sac. The WEB Aneurysm Embolization System is a permanent, self-expanding, mesh ball implant for wide-necked ALs located near branching arteries.

The implant interrupts blood flow into the aneurysm and promotes thrombosis. Its use is indicated for aneurysms in the bifurcation of the ICA, the terminal ICA, the anterior communicating arterial complex, or the apex of the basilar artery (only those that meet certain criteria). This technology does not require antiplatelet therapy and can be applied to ruptured IAs.

It has been proven to be a safe method with a low level of complications. During a 12-month angiographic follow-up, one study showed that 53.8% of patients had complete occlusion of the aneurysm, and that in 84%, the occlusion was considered adequate. The main risks are thromboembolism (2.5%), arterial dissection (0.7%), occlusion of the parent artery (2%), hematoma, infection, reaction to contrast substance and pseudoaneurysms.

Annual morbidity and mortality of 6.4% and 3.1%, respectively, have been reported.

Poor results are more frequent in circulatory AIs and those with a size >12 mm. In terms of durability, successful obliteration was observed in 86.1%, with recurrence in 24.4%, need for retreatment in 9.1%, and annual risk of bleeding in 0.2% of patients. Recanalization may be associated with recurrent bleeding, and the risk is higher in ruptured IAs. However, the recurrence rate with endovascular treatment is higher than that of microsurgical clipping, in terms of disability and complications.

> Conservative treatment

In the absence of symptoms of AINR or a significant family history, or of SAH, most AINR can be managed conservatively, especially in elderly patients. A conservative approach is warranted in patients whose risk of therapeutic complications is greater than the 5-year risk of rupture. These patients should continue to be monitored by imaging and counseled to reduce risk factors for IA growth and rupture.

Controlling blood pressure and stopping smoking is important. It is not necessary to stop routine physical activities or physical exercises and contact sports. Yes, those requiring the Valsalva maneuver (e.g., weight lifting, strenuous exercise) should be stopped.

Other lifestyle modifications (coffee consumption, intercourse) do not justify their suspension, due to the little influence they have on the rupture of IAs of any size. Recently, it has been suggested that several IA groups have a higher risk of growth than others, and in them, the intervals between follow-up scans should be shorter.

The ELAPSS score, based on previous SAH, aneurysm location, age >60 years, population, AINR size and shape, may be a predictor of the risk of aneurysmal growth. Follow-up may not be necessary in patients >75 years of age and those with significant comorbidities or short life expectancy, with large aneurysms, because they are very unlikely to undergo preventive treatment.

There is no evidence that justifies modifying the patient’s lifestyle, except those related to risk factors.

If the AINR size remains stable, observation is recommended. When there is evidence of aneurysmal growth, therapeutic intervention is recommended . The prescription of antiplatelet agents is not clear, but the use of aspirin is suggested, due to its protective effect against the development, progression and rupture of IAs, by attenuating inflammation without worsening the results in patients with aHS.

The PROTECT-U trial is investigating the results of using 100 mg of aspirin. Regarding anticoagulation, although it does not increase the risk of aneurysm rupture, it increases morbidity and mortality due to SAAH. This requires personalized treatment.

Acute AAHS is characterized by extravasation of blood from a ruptured LA into the subarachnoid space. SAH is associated with a substantial burden of morbidity and mortality. The average age of patients with SAH is much younger than for other types of stroke, peaking in the sixth decade, and represents 3% of all types of stroke.

Fatal cases have been decreasing over the years, due to advances in medicine, but the mortality rate remains high (15% and 35%, respectively).

In a retrospective study, the causes of in-hospital death were: initial bleeding, rebleeding, and delayed cerebral ischemia. However, over time, the in-hospital rebleeding rate decreased from 24% to 17%, reducing in-hospital death. It is likely attributed to treatment of a previous aneurysm.

> Epidemiology

In 85% of cases, spontaneous SAH is attributed to ruptured IA. In another 10%, they are perimesencephalic, of unknown etiology. Remaining causes include infection, inflammatory conditions, and vascular malformations.

The global incidence of SAH is estimated to be 6.1/100,000 people. The incidence of SAH has been relatively stable, with a modest decline in recent years. A relationship between SAH and low socioeconomic status has also been observed. Women are doubly affected, but in the younger years the predominance is male.

The most common presentation is a sudden, intense headache, often called a thunderclap headache .

This pain reaches maximum intensity in less than 1 minute and occurs in almost 50% of SAH. On the other hand, SAH is present in 25% of patients with thunderclap headache. This pain is clearly different from other headaches the patient has suffered, and is usually accompanied by loss of consciousness, nausea, vomiting, photophobia, and neck pain. Any new headache with these warning signs deserves further evaluation.

The clinical manifestations of SAH are variable, and a small percentage of patients may experience headache with few or no symptoms. Patients with "sentinel headache" may not seek immediate medical attention, or may be misdiagnosed, with a high risk of bleeding at a later time. The Ottawa HSA rule is a validated tool for use in patients with recent headache.

Includes age ≥40 years, neck pain or stiffness, witnessed loss of consciousness, onset during exertion, maximum instantaneous pain, and limited neck flexion. It has 100% sensitivity and almost 15% specificity for the detection of SAH.

Terson syndrome is recognized as intraocular hemorrhage associated with SAH, which can be diagnosed by fundus examination and is believed to be related to sudden elevation of intracranial pressure. This syndrome is associated with increased mortality and is observed in up to 40% of patients with SAH.

Head CT is the most readily available and appropriate study for the initial diagnosis in patients with suspected SAH. The sensitivity of CT in the first 6 hours after the onset of symptoms can reach 100%.

In most patients with Terson syndrome, head CT shows retinal modularity and crescentic hyperdensities; in patients with normal CT and a high index of suspicion for AAHS, lumbar puncture is recommended.

In a study of patients with SAH-A, all CT scans were normal with a very low prevalence of SAH-A (0.7%). Often, cerebrospinal fluid (CSF) is collected in 4 consecutive tubes, which are inspected directly and then by spectroscopy for xanthochromia. Erythrocytes are also looked for.

In SAH_A, the number of red blood cells in all tubes is comparable while, if the hemorrhage was traumatic, the xanthochromia or red blood cells decrease consecutively. Spectrophotometry is very sensitive (>95%), performed after 12 hours from the onset of SAH, which is why it is recommended by some experts. However, its accuracy has been declining in successive publications.

Vascular imaging is performed after diagnosis of SAH by CT or lumbar puncture. CTA is sufficient in most cases. It should be remembered that 20% of SAH in women is due to multiple IAs.

To determine the culprit aneurysm, it is essential to detect the larger aneurysm by identifying the pattern and epicenter of the SAH on CT. While the larger aneurysm is often blamed, SAH can sometimes be caused by a small aneurysm with irregularities. On the other hand, the pattern and epicenter of SAH may change over time in patients who present late.

Digital subtraction angiography ( DSA) is the gold standard for cerebrovascular imaging and treatment planning, especially in complex cases, as it allows detailed visualization of intracranial vessels. It is very useful for detecting small aneurysms (<2 mm), blister aneurysms, and dissections.

ASD has a low risk of neurological complications and aneurysmal rebleeding. When there is a risk of imminent brain herniation that requires urgent decompression, or in the presence of hematomas that need to be evaluated in the acute phase, CTA alone can be performed, for reasons of time and availability.

CTA can be done during clipping. MRA can identify SAH, but it is not routinely performed in the acute phase due to time and availability limitations. MR imaging of the vessel wall may be useful in identifying the aneurysm that has ruptured in patients with multiple IAs.

MRI may also be useful in evaluating other causes of SAH. Perimesencephalic SAH is a subtype of non-traumatic SAH, with blood mostly isolated to the anterior part of the midbrain or surrounding cisterns, without intraventricular extension.

The clinical course is typically benign, and rebleeding, hydrocephalus, and delayed cerebral ischemia (TBI) are rare, because the origin of the bleeding is not aneurysmal and may also be venous. After perimesencephalic SAH has been ruled out, AI can be found in up to 10% of patients by repeated DSA. 15% to 38% of patients with acute SAH, whose images do not show the source of bleeding, suffer from perimesencephalic SAH.

Once SAH has been ruled out, vascular images will allow us to rule out the presence of AI. The false negative rate of CTA is extremely low, so it is reasonable to forgo ASD after a normal CTA. Despite the reliability of CTA in ruling out IA, some centers advocate doing at least 1 follow-up study with CTA or DSA, due to the possibility that an initial CTA may have given false-negative results.

> Initial treatment

Initial management of patients with SAH should focus on the airway, breathing, and circulation. Patients unable to protect their airways or with acute respiratory illnesses should be intubated immediately.

Due to alterations in the sympathetic nervous system, patients may be at high risk of cardiopulmonary instability. It is necessary to stabilize them in local hospitals and subsequently transfer them to more experienced and equipped centers, with access to intensive care. The first measure is to control blood pressure.

De novo bleeding from the aneurysm has a mortality rate of 20% to 60%, excluding patients who die before arrival at the hospital; It is associated with poor clinical outcome, larger aneurysms, and hypertension.

The highest rate of rebleeding occurs within 72 hours, with the majority (50%-90%) occurring within the first 6 hours, especially when systolic blood pressure is >160 mm Hg.

High blood pressure due to activation of the sympathetic nervous system, pain and anxiety are common . This figure has not emerged from randomized studies, but it is common use to maintain systolic pressure <160 mm Hg so that the aneurysm is secured. Monitoring is often done using an arterial line (NT: a short plastic catheter inserted into the artery), which remains in place until the aneurysm is secured.

The medications are administered intravenously. Hypotension should be avoided due to the risk of cerebral ischemia. Short-acting opioids and acetaminophen are often used for pain control and prevention of secondary hypertension.

There are current reports that gabapentin reduces narcotic requirements. When endovascular obliteration or surgical technique is delayed, and when a patient is transferred to a specialized center, antifibrinolytics (tranexamic acid or ε-aminocaproic acid) are administered short-term to reduce the risk of rebleeding during this vulnerable time.

> Aneurysm treatment

Once clinical stability is achieved, aneurysms should be obliterated as soon as possible, as recommended by the guidelines.

However, there is no consensus on the optimal time to do it, although it is reasonable to do it before reaching 72 hours, when the rate of bleeding and SAH is the highest.

New endovascular techniques and devices allow most ruptured IAs to be treated endovascularly, except aneurysms with hematoma, which require evacuation, and wide-necked aneurysms, which are not suitable for balloon-assisted coiling.

The therapeutic choice depends on the general condition of the patient, the characteristics of the aneurysm, whether there is associated hematoma and mass effect, and deciding whether to use the global microsurgical method or endovascular treatment in an experienced center.

> Increased intracranial pressure (ICP)

It is estimated that more than 50% of patients with SAH have an ICP of 20 mmHg during their hospitalization. Patients with poor clinical status account for 60% to 70% of cases. The sudden onset of hemorrhage, in SAH, increases ICP, which reduces cerebral perfusion pressure (CPP) and can lead to global ischemia or transient cerebral ischemia and circulatory arrest. Apart from the increase caused by aneurysm rupture, ICP also increases in hydrocephalus, which occurs in 20% of patients, in a communicating or obstructive form.

Intraventricular extension of bleeding occurs in up to 50% of patients and may cause obstructive hydrocephalus due to direct blockage of CSF drainage. This leads to further elevation of ICP. The presence of blood within the subarachnoid space impairs CSF absorption through arachnoid granulations, resulting in communicating hydrocephalus.

Increased ICP has always served as a predictor of higher mortality and poor functional outcomes in SAH-A. Despite this, there is no consensus on the management of ICP in SAH-A.

It is commonly caused by brain trauma. For patients with neurological examination findings (e.g., coma), the Brain Trauma Foundation recommends treating elevated ICP and maintaining normal CPP, to prevent neurological deterioration and poor outcomes.

Initial medical treatment involves : elevation of the head between 30º and 45º, in a neutral position, normocapnic ventilation, sedation with or without CSF drainage, and osmotherapy with mannitol or hypertonic saline solution.

The guidelines recommend ICP monitoring for patients with coma Glasgow score ≤8, and diagnosis of traumatic brain injury, to maintain ICP <22 mm Hg and CPP between 60 and 70 mm Hg.

In acute hydrocephalus , insertion of an external ventricular drain can be life-saving. For the management of ICP in SAH-A, hyperosmolar therapy, with mannitol and hypertonic saline, is routinely applied. The gradient at the level of the blood-brain barrier reduces CSF content, and therefore, volume and ICP.

When extrapolating recommendations for SAH-A, the significant clinical, pathophysiological, and hemodynamic differences between SAH-A and traumatic brain injury must be taken into account. Due to its effectiveness in reducing ICP, mannitol remains an option for the treatment of ICP in the setting of SAH-A.

However, it is recommended to use mannitol individually. In contrast to mannitol, hypertonic saline provides intravascular volume expansion, with positive inotropic effects. It has little diuretic effect and can improve both cerebral and systemic hemodynamics.

When hypertonic saline is used, volume status, blood pressure, natremia, and osmolality should be monitored to prevent secondary injury such as TBI. Low-grade hypertonic saline in SAH-A has been shown to increase regional cerebral blood flow, tissue oxygenation, and pH. However, there is no clear evidence on the optimal hyperosmolar treatment for A-SAH.

For intracranial hypertension refractory to initial medical treatment, with the possibility of salvage, decompressive craniectomy or induction of a barbiturate coma can be used. Barbiturates suppress cerebral metabolism with a decrease in ICP. However, this method has many adverse effects hypotension, cardiorespiratory depression and metabolic alterations. It also makes neurological evaluation difficult.

Decompressive craniectomy is a prophylactic and rescue method for various clinical indications with cerebral edema and increased ICP. It also allows reducing compression, evaluating midline changes while improving ICP, CPP and cerebral blood flow.

Early cerebral decompression reduces mortality and improves functional outcomes of malignant ischemic stroke of the middle cerebral artery.

Unlike traumatic brain injury and malignant stroke, the role of brain decompression in SAH-A has not been well established. There are not many studies in this regard, and their results are discordant. Brain decompression can have complications, such as brain herniation and seizures.

> Seizures

Its incidence in patients with SAH is unknown. They often represent a sign of rebleeding prior to aneurysm treatment. The SAFARI score was predictive of an early seizure in a cohort of 1,500 patients. This score uses 4 variables to help determine treatment: age ≥60 years, seizures before hospitalization, SAH with hemorrhage in the anterior circulation, and hydrocephalus requiring external ventricular shunt.

In comatose patients, tonic-clonic seizures are associated with TBI and poor outcomes. Therefore, electroencephalographic monitoring is useful. Despite the lack of evidence, antiepileptics (levetiracetam) are used for seizure prophylaxis, prior to aneurysm treatment. 2% of patients with SAH develop epilepsy.

Fever . Fever in SAH is associated with TBI and poor outcome, regardless of the severity of bleeding or the presence of infection. It occurs in approximately 70% of patients with SAH, especially in high-grade SAH. Fever is often related to systemic inflammatory response syndrome and aseptic chemical meningitis.

Rapid diagnosis and treatment of infectious causes are essential. The combination of pharmacological treatment with external cooling devices is usually sufficient to maintain normothermia.

Fever refractory to treatment during the first 10 days after SAH occurs predicts poor outcome and intraventricular hemorrhage, being associated with greater mortality, functional disability and hypothermia.

> Hypothermia

It is a well-known neuroprotector for those who have survived out-of-hospital cardiac arrest, improving mortality and poor outcomes. It has also been studied in ischemic stroke and transient cerebral ischemia. However, data on the benefits of hypothermia in SAH-A are lacking.

A small pilot project demonstrated the safety and feasibility of therapeutic hypothermia in patients with low-grade SAH, after successful surgical treatment, with a trend towards fewer cases of symptomatic vasospasm, reduced cerebral decompression and better functional and the mortality. However, the differences were not statistically significant.

In one study, the authors concluded that prolonged systemic hypothermia may be considered a last resort in certain patients with refractory increases in ICP or CPP.

In this study, the authors warned of the need to follow protocols, to avoid the adverse effects that occurred, which occur in 93% of treated patients (increased risk of infection, hypovolemia, electrolyte imbalance, insulin resistance, alteration of clearance of drugs and coagulopathy). Currently, hypothermia induced during aneurysm surgery is not routinely recommended.

> Cardiopulmonary complications

Increased catecholamines after SAH-A can cause cardiopulmonary dysfunction, arrhythmias, and stress-induced cardiomyopathy.

Most patients with SAH-A have electrocardiographic abnormalities, such as T wave abnormalities, prolonged QTc intervals, atrial fibrillation. SAH-induced cardiac dysfunction has serious consequences: LV dysfunction, congestive heart failure, and pulmonary edema.

It is often referred to as "neurogenic stunned myocardium" and is associated with a broad spectrum of reversible LV wall motion abnormalities, such as apical akinesia with sparing of basal segments, termed Takotsubo cardiomyopathy , predominant in postmenopausal women and It is often associated with pulmonary edema, prolonged intubation, and TBI. The cornerstone of management lies in optimizing cardiac output to ensure adequate cerebral perfusion.

> Hyponatremia

Hyponatremia is an electrolyte disorder in SAH and should be increased and monitored. Historically, the main contributor was thought to be the syndrome of inappropriate antidiuretic hormone secretion.

However, it is now known that much of the hyponatremia results from cerebral salt wasting (excess urinary sodium and subsequent hyponatremia and dehydration in individuals with intracranial disease), possibly secondary to increased levels of natriuretic peptide. circulating brain.

Due to the previous administration of isotonic and hypertonic solutions (adequate salt loss), management may be difficult in this population. Also in patients potentially affected by a combination of pain-induced, antidiuretic hormone-mediated increases in urinary sodium and brain salt loss. It is emphasized that hyponatremia should never be treated with fluid restriction, since hypovolemia increases the risk of TBI.

> Deep vein thrombosis (DVT)

Patients with SAH are at risk for deep vein thrombosis, presumably due to limited mobility. Pneumatic compression devices are first-line therapy and should be started on admission. Guidelines suggest that it is safe to begin subcutaneous heparin prophylaxis immediately after endovascular clipping and within 24 hours after endovascular clipping.

> Late cerebral ischemia (CTI)

ICT is a major contributor to the outcome of SAH and occurs in 30% to 40% of patients. It defines clinical deterioration in the form of focal deterioration or a decrease of 2 points on the Glasgow Scale during 1 hour, which does not occur immediately after LA occlusion, and cannot be attributed to other causes.

Vasospasm has always been blamed, but late cerebral ischemia is a multifactorial disease, which includes microvascular spasm, microthrombosis, inflammation, and alteration of cerebral autoregulation. The terms vasospasm and ICT are often used interchangeably, but the former is now reserved for angiographic description.

The diagnosis of TBI and vasospasm requires frequent neurological, neuroimaging, and other multimodal follow-up methods. In patients with SAH, TBI should be suspected when focal or global neurological deficits appear.

Transcranial Doppler ultrasound is routinely performed for monitoring vasospasm while monitoring for ischemia is done by imaging the cerebral vessels, with or without perfusion.

New hypodensities on CT not attributable to the insertion of an external ventricular shunt or treatment of an aneurysm should be considered infarction secondary to TBI, regardless of the clinical picture. The gold standard for the detection of vasospasm of medium and large arteries remains DSA.

The fundamental treatment of TBI is prophylaxis with nimodipine and maintenance of normal intravascular volume. It is the only medical treatment for SAH-A that improves outcomes. An adverse effect of nimodipine is hypotension and therefore decreases CPP. It can also cause bradyarrhythmia. The variability of its effect may depend on your particular metabolism.

To prevent TBI, in all SAH-A patients, the mainstay of treatment is to maintain euvolemia. In ICT, control of high blood pressure is important. Triple-H therapy (hypertension, hypervolemia, and hemodilution) is a traditional therapeutic method for acute TBI. However, therapy now focuses more on the prevention of hypovolemia and hypertension, given the increased risk of adverse outcomes from hemodilution and its cardiopulmonary consequences.

The HIMALAIA trial, which investigated the role of induced hypertension in ICT, did not demonstrate any benefit. This trial was terminated early due to negative results and slow recruitment. There are no conclusive data on the effect of specific vasopressors. Usually, the vasoconstriction they cause is limited to the systemic vessels.

TBI with focal deficits is treated with vasodilators (verapamil or nicardipine) introduced into the affected arterial tree, with balloon angioplasty, in medium and large vessels. However, the use of intraventricular nimodipine is not widely accepted.

There are scales that allow grading the severity of the neurological disorders caused by SAH, and thus be able to make a prognosis of the evolution and plan treatment.

There are several scales, including the PAASH bleeding scale, the modified Fisher grading, and the Hunt and Hees grading. The latter continues to be the most applied for HSA-A