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    Apr.15.2021

    Cerebral Aneurysm

    Synopsis

    Key Points

    • Cerebral aneurysm is focal dilation of a cerebral artery usually caused by a weakening or thinning of the vessel wall. May be ruptured or unruptured and is classified according to size and shape
      • Ruptured cerebral aneurysms can lead to stroke, brain damage, or death
    • Symptoms of ruptured intracranial aneurysms classically include sudden-onset, severe headache ("worst headache of my life") often associated with nausea and/or vomiting, photophobia, stiff neck, brief loss of consciousness, or focal neurologic deficits (including cranial nerve palsies) r1
      • Patients with an unruptured intracranial aneurysm are frequently asymptomatic
    • Noncontrast head CT is the first line diagnostic test when a ruptured aneurysm is suspected, followed by lumbar puncture to assess for xanthochromia if CT is inconclusive r1r2
      • After confirmation of hemorrhage, further imaging is obtained to detect and characterize ruptured cerebral aneurysm. Catheter arteriography remains the gold standard in aneurysm evaluation
    • Diagnosis of unruptured intracranial aneurysm is often incidental. When history suggests the possibility, CT angiography and magnetic resonance angiography are the preferred diagnostic imaging modalities r3r4
      • Screening for intracerebral aneurysm is beneficial only in populations with a higher expected prevalence and higher risk of rupture
    • Treatment of a ruptured intracranial aneurysm requires immediate attention and can require surgical, endovascular, and drug therapies, including control of hypertension, hyponatremia, seizures, and vasospasm, as well as correction of coagulation factors and general medical support r1r2
    • Treatment of an unruptured intracranial aneurysm is focused on preventing rupture and may be conservative with routine monitoring or active with surgical or endovascular intervention; choice is based on patient age and many other factors r4
    • Main complications of ruptured aneurysm include rebleeding, delayed cerebral ischemia from vasospasm, and hydrocephalus
    • Including patients who die before medical attention, 43% of all patients with subarachnoid hemorrhage die without recovering from the initial bleeding r5
      • Despite treatment, ruptured aneurysms are associated with fatality in one-third of cases and with severe disability in one-sixth of cases r5
      • 12% of patients will die before getting medical attention

    Urgent Action

    • Aneurysmal subarachnoid hemorrhage is a medical emergency requiring immediate care and evaluation
    • Monitor all patients for clinical status using a validated assessment scale
      • Begin preparation for transfer to specialized care and/or a specialized facility on admission to the emergency department
    • Immediate medical support includes the following:
      • Adequate oxygenation and airway management without hyperventilation
      • Control of hypertension, seizures, hyperglycemia, and fever
      • Fluid management to maintain a normovolemic state
      • Correction of coagulation disorders

    Pitfalls

    • Subarachnoid hemorrhage may be preceded by a sentinel headache in 20% of patients (from aneurysm leakage before rupture). The majority of these occur within 2 to 8 weeks of the rupture r1r6
    • Imaging findings, including CT or MRI, may be negative with delay in evaluation, and evaluation of spinal fluid for xanthochromia may be required to make the diagnosis

    Terminology

    Clinical Clarification

    • Cerebral aneurysm is focal dilation of a cerebral artery usually caused by weakening or thinning of the vessel wall; may be ruptured or unruptured and is classified according to size and shape r7
      • Ruptured cerebral aneurysms can lead to stroke, brain damage, or death r5
    • Most commonly found in the subarachnoid space
    • Multiple aneurysms are present in 10% to 30% of patients r8

    Classification

    • Aneurysm status r9
      • Unruptured intracranial aneurysm
        • Often discovered during evaluation for other conditions such as headache, stroke, transient ischemic attack, or seizure r10
      • Ruptured intracranial aneurysm r9
        • Most often presents as frank subarachnoid hemorrhage with severe headache
        • Patients with leaking ruptured aneurysm may present with less severe symptoms and signs
        • If left untreated, may be life-threatening r11
    • Aneurysm shape r9
      • Fusiform aneurysm
        • Spindle-shaped widening of the vessel wall, without a distinct neck
        • Subclassification based on presence or absence of branch vessel involvement
        • Represents 5% of unruptured aneurysms r9
      • Saccular aneurysm
        • Pouchlike form with a distinct neck
        • Subclassification based on presence or absence of branch vessel involvement
        • Represents 95% of unruptured aneurysms r9
    • Aneurysm size r12
      • Very small: less than 3 mm
      • Small: 3 to 6 mm
      • Small-medium: 7 to 12 mm
      • Large: 13 to 25 mm
      • Giant: larger than 25 mm

    Diagnosis

    Clinical Presentation

    History

    • Patients with an unruptured intracranial aneurysm are frequently asymptomatic r4c1
      • Aneurysms smaller than 7 mm in diameter are the most frequently detected overall but are unlikely to cause symptoms r4
      • Unruptured intracranial aneurysm can be found incidentally during evaluation for unrelated disorders/complaints (eg, hemorrhage from another intracranial aneurysm, headache, stroke, transient ischemic attack) r13
      • Most common symptoms of an unruptured intracranial aneurysm include the following: r13
        • Headache c2
        • Focal neurologic deficits including visual changes (eg, diplopia, visual field defects) c3c4c5
        • Seizure c6
    • Patients with ruptured intracranial aneurysms present with symptoms that are sudden and severe (occurring over minutes or hours) r1
      • Severe headache ("worst headache of my life") (80%) r1c7
        • Thunderclap headache (extremely sudden and immediately reaching maximum intensity) c8
        • Preceded by sentinel headache in 20% of cases, caused by aneurysm leaking before frank rupture occurs r1r6c9
          • Majority of these severe headaches occur within 2 to 8 weeks of rupture
      • Headache may be accompanied by 1 or more signs and symptoms including:
        • Nausea and/or vomiting (77%) r1c10c11
        • Loss of consciousness (53%); may progress to coma r1c12c13
        • Stiff neck (35%) r1c14
        • Diplopia or vision loss c15c16
        • Photophobia c17
      • In most cases, rupture is spontaneous; however, some ruptures may be precipitated by activities associated with a sudden increase in blood pressure, such as blowing nose, sexual activity, defecation, vigorous exercise, or anger r8

    Physical examination

    • Unruptured aneurysm
      • Most often asymptomatic without abnormal physical findings r4
      • Unruptured aneurysm may cause a mass effect, presenting as 1 or more of the following: r4r10
        • Cranial nerve palsy (most commonly a third nerve palsy) and/or unilaterally dilated pupil c18c19c20
        • Cerebellar signs c21
        • Syncope c22
        • Other focal neurologic findings, including stroke c23
        • Neurologic findings without rupture may occur in 11% of patients r13c24
    • Ruptured intracranial aneurysm (subarachnoid hemorrhage)
      • May present with 1 or more of the following:
        • Altered consciousness (up to loss of consciousness) r2c25c26
          • Evaluation includes a standardized severity score such as: r1r2
            • Intracerebral Hemorrhage score r1r14
            • NIH Stroke scale r15
            • Hunt and Hess scale r1r2
        • Focal neurologic findings r16
          • Cranial nerve palsy and/or unilaterally dilated pupil c27c28
          • Cerebellar signs c29
          • Syncope c30
          • Other focal neurologic findings, including stroke c31
        • Constricted pupils r16c32
        • Nuchal rigidity r16c33
        • Seizures may occur in up to 20% of patients r1c34
          • Typically within the first 24 hours. More commonly associated with intracerebral hemorrhage, hypertension, and aneurysms of the middle- and anterior-communicating artery

    Causes and Risk Factors

    Causes

    • Exact cause of intracranial aneurysm is unknown c35

    Risk factors and/or associations

    Age
    • Frequency of aneurysm development increases with age, with peak in the fifth and sixth decades of life r4r8c36c37c38c39c40c41
    • Growth rate of existing intracranial aneurysm is faster in younger people r4c42c43c44c45c46
    Sex
    • Overall incidence is higher in women, with 3 to 1 female to male ratio r4r10c47c48
      • Males and females equally affected below the age of 40 years r8
    • Relative risk for growth is higher in females by a factor of 2.3 r4r17c49c50
    Genetics
    • Autosomal dominant inheritance pattern occurs in some patients r4c51
    • Several genes or chromosomal regions have been identified in both familial and sporadic cases of intracranial aneurysm r4r18
    • Incidence is approximately 7% to 20% in people with family members who have had an aneurysm r4c52
    Ethnicity/race
    • In the United States, American Indian, Alaskan native, Asian Pacific Islander, and Black populations have a higher mortality rate from ruptured aneurysms compared with White populations r4c53c54c55c56c57
    • Patients in Japan and Finland have an increased risk of an aneurysm rupture; however, it is unclear whether this is attributable to ethnicity or rather a result of exposure to environmental risk factors in those geographic regions r8r19c58c59
    Other risk factors/associations r4
    • For development of intracranial aneurysm
      • Cigarette smoking c60c61
        • 36% to 61% of patients with unruptured intracranial aneurysm are current smokers, and 19% to 33% are former smokers r4
      • Hypertension c62
        • Hypertension may be a risk factor for aneurysm development; however, there is little evidence that control of hypertension reduces the risk of aneurysm development r4
      • Alcohol use c63
        • Excessive alcohol use (more than 150 g/week) increases the risk of aneurysm formation independent of sex, age, cigarette smoking, and history of hypertension r5
      • Disorders associated with increased risk for aneurysm development are as follows, although together represent less than 10% of patients presenting with an unruptured aneurysm: r4
        • Polycystic kidney disease (3- to 14-fold increased risk) r4c64
        • Connective tissue and skin disorders, including Marfan syndrome, pseudoxanthoma elasticum, type IV Ehlers-Danlos syndrome, and fibromuscular dysplasia c65c66c67c68c69c70
        • Vascular anomalies, including coarctation of the aorta, bicuspid aortic valve, and intracranial arteriovenous malformations c71c72c73c74
        • Enzyme deficiencies including α1-antitrypsin deficiency and α-glucosidase deficiency c75c76c77
        • Hereditary hemorrhagic telangiectasia c78
        • Neurocutaneous disorders, including neurofibromatosis type 1, tuberous sclerosis, and pheochromocytoma c79c80c81c82
        • Dysmorphic disorders, including Noonan syndrome and microcephalic osteodysplastic primordial dwarfism c83c84
        • Klinefelter syndrome c85
    • For growth of existing intracranial aneurysm
      • Characteristics of aneurysm r4
        • Location r20r21
          • Aneurysms in the posterior circulation are more likely to grow c86
        • Shape r21
          • Aneurysms with lobulations are more likely to grow c87
        • Size r22
          • Aneurysms that are larger at diagnosis are more likely to grow than smaller aneurysms c88
        • Multiple aneurysms c89
      • Cigarette smoking r4c90
      • Hypertension r4c91
      • Alcohol use r23c92
      • History of stroke or transient ischemic attack c93c94
    • For rupture of intracranial aneurysm/subarachnoid hemorrhage
      • Cigarette smoking c95
        • Relative risk for subarachnoid hemorrhage for current smokers is 2.2 to 3.1 compared with nonsmokers r5
        • 40% of aneurysms with subarachnoid hemorrhage can be attributed to cigarette smoking r5
      • Hypertension r4c96
        • May be a risk factor for aneurysm rupture with an odds ratio of 1.5 to 2.4 r24
      • Alcohol use c97
        • Excessive alcohol use (more than 150 g/week) is a risk factor for aneurysm rupture r5
      • Illicit drug use c98c99
        • Cocaine use is associated with hemorrhage of intracranial aneurysms at younger age and with smaller aneurysm than the overall population with hemorrhage r25r26
          • Mean age at rupture is 31 years r26

    Diagnostic Procedures

    Primary diagnostic tools

    • Diagnosis of suspected ruptured aneurysm (acute subarachnoid hemorrhage) is based on the following: c100
      • History typically includes sudden-onset severe headache, maximal at onset, and dissimilar to previous headaches r2r27
      • Physical findings, particularly: r2r16
        • Altered/deteriorating level of consciousness
        • Focal neurologic findings
        • Nuchal rigidity
      • Perform noncontrast head CT as the initial imaging modality r1r2r3c101
        • Test of choice to evaluate for suspected subarachnoid hemorrhage r3
          • Sensitivity of CT in the first 3 days after acute subarachnoid hemorrhage approaches 100% r1
      • If imaging study results are negative, perform lumbar puncture for cerebrospinal fluid analysis to detect xanthochromia and confirm subarachnoid hemorrhage r1c102
        • Rate of negative CT study results increases sharply after 5 to 7 days, and lumbar puncture is often required to show xanthochromia
        • Alternatives to lumbar puncture to evaluate for suspected subarachnoid hemorrhage after negative noncontrast head CT study results are more controversial
          • Can consider CT angiography after nondiagnostic noncontrast head CT finding. May be appropriate when lumbar puncture is difficult or not feasible, patient refuses lumbar puncture, or results of lumbar puncture are equivocal r1r27r28c103
            • A drawback of vascular imaging is discovery of aneurysms that are not the cause of the headache; exposes patient to risks of additional testing and potentially unnecessary procedures r27
          • MRI, with fluid-attenuated inversion recovery, proton density, diffusion-weighted imaging, and gradient echo sequences, may be reasonable to diagnose acute subarachnoid hemorrhage when CT scan result is nondiagnostic and clinical suspicion of acute subarachnoid hemorrhage remains r1c104
            • A negative result does not eliminate the need for cerebrospinal fluid analysis
      • After confirming hemorrhage using noncontrast CT or lumbar puncture, obtain further imaging to detect and characterize ruptured cerebral aneurysm (cause of 80%-90% of nontraumatic hemorrhage) r1r3
        • Can include catheter angiography, CT angiography, or magnetic resonance angiography c105
          • Digital subtraction catheter angiography is the gold standard diagnostic tool for detecting aneurysms r3r29
            • Best able to recognize small aneurysms
              • Small aneurysms (less than 3 mm in diameter) account for almost one-third of ruptured aneurysms r3
          • Noninvasive imaging with CT angiography or magnetic resonance angiography are alternatives but have lower sensitivities for detecting small aneurysms (smaller than 3 mm) r3
            • CT angiography is increasingly being used instead of arteriography; however, negative predictive value in this setting is poor r3
              • In patients with negative CT angiography study results, performing catheter angiography can result in detection of the causative lesion in 15% of those with diffuse subarachnoid hemorrhage and 9% of those with sulcal subarachnoid hemorrhage r3
            • Magnetic resonance angiography has sensitivity similar to CT angiography, does not require IV contrast, and may be useful in certain patients (eg, those with renal dysfunction or iodine allergy)
        • If initial imaging study result is negative (ie, owing to small aneurysm size, aneurysm thrombosis, local vasospasm, incomplete study): r3
          • Obtain CT angiography or magnetic resonance angiography if digital subtraction angiography was the initial study
          • Obtain digital subtraction angiography if CT angiography or magnetic resonance angiography was initially performed
          • If both initial digital subtraction angiography and noninvasive study results are negative, repeat digital subtraction angiography in 1 to 2 weeks
    • Diagnosis of unruptured aneurysm is based on the following:
      • Unruptured intracranial aneurysm is often an incidental diagnosis with evaluation for unrelated complaints or complaints related to increasing size of the aneurysm compressing nearby brain structures r4
        • History and physical examination may suggest diagnosis
      • Imaging studies confirm diagnosis
        • Noninvasive CT angiography and magnetic resonance angiography are preferred for identification of unruptured intracranial aneurysm r3r4
          • CT angiography has higher spatial resolution but requires IV contrast and exposes patient to radiation
          • Magnetic resonance angiography lacks ionization and does not require IV contrast but may not be feasible in some patients (eg, obese, claustrophobic, or with those with metal implants)
        • Digital subtraction angiography may be considered over noninvasive imaging if surgical or endovascular treatment is being considered r4

    Laboratory

    • Cerebrospinal fluid analysis r30c106
      • Diagnosis of subarachnoid hemorrhage with a normal CT scan result is confirmed when xanthochromia is present in cerebrospinal fluid
        • Xanthochromia is a reliable sign if obtained at least 12 hours after subarachnoid hemorrhage
          • Takes several hours to appear after bleeding begins (20% of patients at 6 hours) and can last for up to 2 weeks r28
        • Spectrophotometric analysis of centrifuged cerebrospinal fluid is more accurate than visual inspection in detecting xanthochromia r31

    Imaging

    • Imaging studies
      • Noncontrast CT c107
        • Initial imaging test of choice to evaluate for suspected subarachnoid hemorrhage/ruptured intracerebral aneurysm r1r3
          • Sensitivity of CT in the first 3 days after acute subarachnoid bleed is very high (near 100%), after which it decreases moderately over the next few days r1
        • Advantages include high sensitivity for acute hemorrhage, wide 24-hour availability, no absolute contraindications, fast image acquisition, and ease of patient monitoring
      • Digital subtraction angiography (catheter arteriography) r4c108
        • Preferred technique of cerebral angiography. Allows computer-assisted radiographic visualization of cerebral vessels with minimal view of background tissues
        • Invasive imaging test with potential complications. Risks of catheter angiography (though small) include cerebral infarction, aneurysm rupture, arterial injury, and contrast-related events r4
          • In patients with renal insufficiency or Ehlers-Danlos syndrome, risks with catheter angiography are higher so noninvasive imaging should be considered
        • Gold standard for diagnosis and localization of aneurysm in subarachnoid hemorrhage r1r3
          • Able to identify very small aneurysms (smaller than 3 mm) and lesions (eg, perforating arteries in very small vessels) r4
          • Has sensitivity above 90% (falls to slightly greater than 80% in the setting of acute subarachnoid hemorrhage) r3
        • Preferred imaging study for follow-up of previously treated aneurysms
          • Compared with noninvasive imaging alternatives, is least likely to be affected by artifacts from earlier treatment
        • Not an appropriate screening test given its invasiveness (except in patients who have had previous aneurysm treatments) r3
          • Can be useful over noninvasive imaging if surgical or endovascular treatment is being considered r4
      • CT angiography c109
        • Advantages include rapid image acquisition, low motion susceptibility, availability, and relatively high spacial resolution r3
        • Limitations include patient exposure to ionizing radiation. Injection of IV iodinated contrast material incurs risk for contrast allergy and contrast-induced nephropathy
        • Overall sensitivity in detection of aneurysms is 85% to 95%. This is lower in the setting of diffuse subarachnoid hemorrhage r3
        • Importantly, sensitivity for smaller aneurysms (smaller than 3-mm diameter) is much lower (around 55%); these can account for almost one-third of ruptured aneurysms r3
          • CT angiography may not accurately depict small vessel anatomy, which can be an important determinant of treatment decisions r32
        • Indications include
          • Following nondiagnostic noncontrast head CT result, consider excluding aneurysmal subarachnoid hemorrhage when lumbar puncture is difficult or not feasible, refused by patient, or results are equivocal r1r27
          • Alternative (second line) to catheter angiography to detect and characterize ruptured cerebral aneurysm r3
          • Screening tool for unruptured aneurysms for at-risk populations r3r4
      • Magnetic resonance angiography c110
        • Advantages include lack of ionizing radiation and lack of need for IV contrast
        • Limitations include decreased routine availability, logistics (eg, difficulty in scanning acutely ill patients), predisposition to motion artifact, patient compliance, and longer study time r1
        • Comparable overall sensitivity to CT angiography in the detection of intracranial aneurysms r3
          • Magnetic resonance angiography likely has slightly inferior specificity
          • Similar to CT angiography, shown to have difficulty with aneurysms smaller than 3 mm r3
          • No significant differences in the performances of contrast-enhanced and noncontrast magnetic resonance angiography examinations
        • Indications include
          • Alternative (second line) to catheter angiography to detect and characterize ruptured cerebral aneurysm r3
          • Screening tool for unruptured aneurysms in at-risk populations r3r4
      • MRI c111
        • MRI (fluid-attenuated inversion recovery, proton density, diffusion-weighted imaging, gradient echo sequences) may be reasonable for diagnosis of subarachnoid hemorrhage in patients with a nondiagnostic CT scan result, although a negative result does not obviate need for cerebrospinal fluid analysis r1
        • MRI is as sensitive as CT for detection of acute hemorrhage and is more sensitive for identification of prior hemorrhage r2
        • Time, logistics, patient tolerance, clinical status, and availability often preclude emergent MRI r2
      • Catheter angiography c112

    Procedures

    Lumbar puncture c113
    General explanation
    • Insertion of a hollow-bore needle between the vertebral bodies into the subarachnoid space to obtain a specimen of cerebrospinal fluid or to measure opening pressure
    Indication
    • To collect and examine cerebrospinal fluid for evidence of subarachnoid hemorrhage (xanthochromia) after negative imaging study results
    Contraindications
    • Uncontrolled coagulopathy
    • Skin infection at site of needle insertion
    • Patient at risk of brain herniation
      • Best predictors of precipitating herniation (despite normal CT scan result) include the following:
        • Deteriorating level of consciousness (particularly to a Glasgow Coma Scale score of 11 or less)
        • Brainstem signs (eg, pupillary changes, abnormal posturing, irregular respirations)
        • Very recent seizure
    Complications
    • Post–dural puncture headache
    • Radicular injury
    • Infection (eg, epidural abscess, meningitis, diskitis, vertebral osteomyelitis)
    • Epidural hematoma
    • Cerebral herniation
    Interpretation of results
    • Xanthochromia is a reliable sign if obtained at least 12 hours after subarachnoid hemorrhage r1r5
    • Within the first 6 to 12 hours, the differentiation between genuine subarachnoidal blood and traumatic admixture of blood may be difficult
    • Spectrophotometric analysis of centrifuged cerebrospinal fluid is more accurate than visual inspection in detecting xanthochromia r31

    Differential Diagnosis

    Most common

    • Migraine headache r10c114d1
      • Migraine can cause moderate to severe localized, often unilateral pain, accompanied by nausea and vomiting that is similar to symptoms of ruptured cerebral aneurysm
      • Patients with migraine often have a history of recurrent headaches in the same location and of specific triggers preceding the headache
      • Noncontrast CT scan result will be normal with migraine
    • Stroke or transient ischemic attack r4c115c116d2
      • Patient may present with transient or fixed neurologic deficit, as with intracerebral aneurysm, but usually without headache
      • CT and MRI confirm absence of subarachnoid hemorrhage or aneurysm. MRI may show evidence of transient ischemia during a transient ischemic attack
    • Cerebral venous sinus thrombosis r33c117
      • Acute thrombosis in the dural venous sinuses cause headache, abnormal vision, and facial weakness similar to symptoms of cerebral aneurysm
      • Focal or generalized seizures are frequent, occurring in 40% of cases r33
      • Headache is present in nearly 90% of cases and is typically diffuse r33
        • Often progresses in severity over days to weeks
        • A minority of patients experience thunderclap headache
        • Migrainous headaches have been described
      • Patients with cerebral venous sinus thrombosis also may present with papilledema or diplopia (caused by sixth nerve palsy)
      • Diagnosis is confirmed by imaging with contrast-enhanced MRI, CT venogram, or magnetic resonance venogram
      • Differentiated by imaging that shows hyperdensity of a cortical vein or dural sinus by CT, or detection of thrombus in a venous sinus by MRI
    • Meningitis r34c118d3
      • Bacterial meningitis most commonly causes vomiting, headache, and nuchal rigidity similar to cerebral aneurysm d4
      • Differentiated by presence of fever without thunderclap headache and cerebrospinal fluid results indicating bacterial infection
    • Cerebral vasoconstriction syndrome r35r36c119
      • Condition caused by arterial constriction and dilation
      • Can mimic subarachnoid hemorrhage with thunderclap headache
      • CT angiography or magnetic resonance angiography confirms arterial segmental vasoconstriction

    Treatment

    Goals

    • Regular monitoring for growth or treatment of an unruptured intracranial aneurysm is aimed at preventing rupture
    • For ruptured aneurysm, minimize brain injury and prevent life-threatening sequelae r2

    Disposition

    Admission criteria

    Admit patients with suspected symptomatic unruptured intracranial aneurysm to the hospital for observation, diagnosis, and treatment r4

    All ruptured intracranial aneurysms require immediate transfer to the emergency department r2

    • A multidisciplinary team determines whether a patient is a candidate for transfer to a stroke unit or to a neuroscience ICU with operative capability r2
    Criteria for ICU admission
    • Virtually all patients with ruptured intracranial aneurysm are admitted to ICU

    Recommendations for specialist referral r5

    • Transfer patients to the care of neurologist, neurosurgeon, and interventional neuroradiologist for definitive diagnosis, treatment, and management of cerebral aneurysm (both unruptured and ruptured)
    • Surgical treatment of unruptured intracranial aneurysm should be done at higher-volume centers (treating more than 20-35 cases annually) r1r4

    Treatment Options

    Treatment of ruptured intracranial aneurysm

    • Definitive treatment is urgent surgical or endovascular intervention
      • Obtain emergent multidisciplinary consultation (neurosurgeon and interventional radiologist)
      • Determine aneurysm treatment with a multidisciplinary team, considering patient's individual requirements and aneurysm characteristics r1
      • Begin procedures to transport patient to specialized treatment center if appropriate
      • Determine patient's candidacy for aneurysm repair based on severity of initial bleed, time to admission, blood pressure, sex, aneurysm characteristics, hydrocephalus, angiography results, and presence of a ventricular drain r1r2
      • Choice of intervention is determined by patient's age, comorbid conditions, aneurysm characteristics, and severity of hemorrhage and neurologic compromise r1r2
      • If patient is a candidate for repair, proceed to surgical clipping or endovascular coiling of the ruptured aneurysm as soon as possible to reduce rate of rebleeding r1r2
        • Endovascular coiling is the most common approach to repair and has the highest level of evidence for benefit r29
      • Increased time to treatment is associated with increased rates of preoperative rebleeding and poor outcome r1
    • Placement of a ventricular drainage catheter
      • Ventricular drainage as treatment of elevated intracranial pressure secondary to hydrocephalus is recommended, especially in patients with decreased level of consciousness r2
    • Use adjunctive medical therapies to prevent rebleeding r1r2
      • Guidelines recommend treatment of severe hypertension with β-blockers or calcium channel blockers: labetalol, esmolol, and nicardipine r1
        • For systolic blood pressure ranging from 150 to 220 mm Hg and without contraindication to acute blood pressure treatment, acute lowering of systolic blood pressure to 140 mm Hg is safe r1r2
          • Optimal blood pressure to reduce risk of rebleeding in subarachnoid hemorrhage has not been established r1
        • For systolic blood pressure over 220 mm Hg, aggressive blood pressure reduction with a continuous IV infusion is recommended r2
      • Treatment with antifibrinolytic agents for less than 72 hours is recommended for patients with delay in treatment of aneurysm, risk of rebleeding, and without contraindications to reduce risk of early aneurysm rebleeding r1
        • Neither aminocaproic acid nor tranexamic acid is FDA approved for prevention of aneurysm rebleeding
    • Treat with calcium channel blocker to prevent delayed cerebral injury r1
      • Administer oral nimodipine to all patients with acute subarachnoid hemorrhage r29
    • Treat seizures with anticonvulsants r2
      • Seizure prophylaxis with anticonvulsants is not recommended
    • Provide ongoing general medical support r1r2
      • Manage patients with subarachnoid hemorrhage in an ICU or dedicated stroke unit
      • Oxygenation and airway management
        • Maintain oxygenation without hyperventilation and periodically assess with oximetry and arterial blood gases
      • Assess clinical condition initially and continuously with use of a validated scale (eg, Intracranial Hemorrhage Scale, NIH Stroke scale, Hunt and Hess scale)
      • Manage fluids to maintain normovolemia to prevent delayed cerebral ischemia
      • Manage glucose management to prevent hypo- and hyperglycemia
      • Replace coagulation factors for patients with a severe coagulation factor deficiency, or platelets for patients with severe thrombocytopenia
      • Hold vitamin K antagonists, replace vitamin K–dependent factors, and correct INR with IV vitamin K in patients with elevated INR
      • Control fever
      • Monitor sodium level. Treat hyponatremia with infusion of 3% saline solution or with fludrocortisone r1r37
      • Place intermittent pneumatic compression for prevention of venous thromboembolism beginning the day of hospital admission r2

    Treatment of an unruptured intracranial aneurysm r4r10

    • Preventive aneurysm repair eliminates the risk of aneurysm rupture but carries approximately 6% to 10% risk of poor neurological outcome. For most aneurysms, this is higher than the risk of rupture
    • The decision of whether or not to perform preventive repair of an unruptured aneurysm should be undertaken by a multidisciplinary cerebrovascular team taking into consideration the risk factors for aneurysm rupture and risks associated with repair
    • Risk for aneurysm rupture can be predicted based on the following: r38r39
      • Aneurysm characteristics r39
        • Size (diameter, perpendicular height)
        • Shape
        • Location
        • Aneurysm to parent vessel size ratio
        • Growth on follow-up
      • Patient characteristics associated with increased risk for rupture r19
        • Presence of multiple aneurysms
        • Hypertension
        • History of subarachnoid hemorrhage
        • Cigarette smoking
        • Family history of cerebral aneurysms
        • Heavy alcohol intake
        • Stimulant use
        • Female sex
        • Younger age (higher cumulative long-term risk because of long life expectancy in younger patients)
      • Geographic region (higher risk in Japan and Finland compared to North America and Europe) r40
    • Scoring systems such as PHASES score and unruptured intracranial aneurysm treatment score based on these risk factors can be used to aid in prediction of the risk of aneurysm rupture r40r41r42
    • Generally, conservative management (ie, regular monitoring with imaging) is appropriate for patients with small asymptomatic aneurysms (smaller than 5-7 mm) and who are not at increased risk of rupture, taking into consideration aneurysm-related symptoms, age, and comorbidities r4r43r44
      • Treat any modifiable risk factors, such as hypertension, and counsel regarding smoking cessation and reduction in heavy alcohol consumption r19
        • Daily low-dose aspirin is safe to use in patients with small unruptured aneurysms and may reduce aneurysm wall inflammation and risk of rupture r45
    • Surgical management is usually appropriate for patients with large (larger than 7-10 mm) or symptomatic aneurysms (causing compressive symptoms or embolic stroke) or small (smaller than 5-7 mm) aneurysms with increased risk of rupture r4r44
      • Many experts also endorse routine treatment of aneurysms between 5 and 7 mm in size r44
      • The optimal treatment modality for preventive repair has not been definitely established r19
        • Endovascular coiling r4r10
          • Patient age; aneurysm location, size, shape, risk of rupture, presence of symptoms; and medical comorbidities should be taken into account when endovascular coiling for an unruptured intracranial aneurysm is being considered
          • Endovascular coiling is more appropriate as first line strategy in older patients or patients with comorbidities, and for aneurysms involving the posterior circulation r19
          • Associated with lower morbidity and mortality but a higher risk of recurrence than surgical clipping r8
        • Microsurgical clipping r4r10
          • Patient age; aneurysm location, size, shape, risk of rupture; presence of symptoms; and medical comorbidities should be taken into account when surgical clipping for an unruptured intracranial aneurysm is being considered
          • Surgical clipping, especially for wide-neck aneurysms, may be more appropriate for younger patients owing to its higher occlusion rates and longer durability r19
        • Use of endoluminal flow diversion and liquid embolic agents are additional techniques in development but are not guideline recommended r4

    Drug therapy

    • Calcium channel blockers r1r2
      • Nicardipine c120
        • Nicardipine Hydrochloride Solution for injection; Adults: 5 mg/hour continuous IV infusion, initially. Titrate by 2.5 mg/hour every 5 to 15 minutes until goal blood pressure is attained. Max: 15 mg/hour.
      • Nimodipine c121
        • Nimodipine Oral capsule, liquid filled; Adults: Initially, 60 mg PO q4h for 21 consecutive days. Begin therapy within 96 hours of SAH.
    • β-blockers r1r2
      • Labetalol c122
        • Intermittent
          • Labetalol Hydrochloride Solution for injection; Adults: 10 to 20 mg IV, then 20 to 80 mg IV every 10 to 30 minutes until goal blood pressure is attained. Max cumulative dose: 300 mg.
        • Continuous Infusion
          • Labetalol Hydrochloride Solution for injection; Adults: 10 to 20 mg IV, then 0.5 to 2 mg/minute continuous IV infusion initially. Titrate every 15 minutes until goal blood pressure is attained. May repeat or double bolus dose after 10 minutes before starting infusion. Max: 10 mg/minute. Max cumulative dose: 300 mg.
      • Esmolol c123
        • Esmolol Hydrochloride Solution for injection; Adults: 500 to 1,000 mcg/kg IV over 1 minute, then 50 mcg/kg/minute continuous IV infusion, initially. Repeat bolus and titrate by 50 mcg/kg/minute until goal blood pressure is attained. Max: 200 mcg/kg/minute.
    • Anticonvulsants r2
      • Lorazepam c124
        • Lorazepam Solution for injection; Adults: 4 mg IV at a rate of 2 mg/minute; may give a second dose in 10 to 15 minutes if needed. Experience is limited with further doses.
      • Fosphenytoin c125
        • Fosphenytoin Sodium Solution for injection; Adults: 15 to 20 mg PE/kg IV load; may give an additional 5 to 10 mg PE/kg after the initial load; Max total load: 30 mg PE/kg.
    • Corticosteroids
      • Fludrocortisone c126
        • Fludrocortisone Acetate Oral tablet; Adults: 0.3 mg PO once daily. r37c127

    Nondrug and supportive care

    Hydration with isotonic saline r1r2c128

    • Infuse isotonic saline to maintain euvolemia to prevent delayed cerebral ischemia c129

    Glucose management c130

    • Target glucose level and optimal management of hyperglycemia in the setting of ruptured aneurysm remain to be clarified r2
    • Avoid hypoglycemia

    Control of hyponatremia c131

    • Administer corticosteroids and infusion of 3% hypertonic saline to control hyponatremia
    Procedures
    Microsurgical clipping r10c132
    General explanation
    • Aneurysm is dissected and a small metallic clip is placed at the neck of the aneurysm to isolate it from the parent blood vessel r10
    Indication
    • For unruptured intracranial aneurysm r4
      • Consider patient age; aneurysm location, size, shape, and risk of rupture; symptoms; and medical comorbidities into account when surgical clipping for an unruptured intracranial aneurysm is being considered
      • Preferred option for younger patients (younger than 50 years), smaller aneurysms (smaller than 10 mm), aneurysms in the anterior circulation, and when aneurysm shape or size makes complete occlusion by endovascular coiling unlikely
      • In the absence of prohibitive comorbidities, offer treatment to patients with unruptured intracranial aneurysm who have had enlargement documented during follow-up
      • Treatment of unruptured intracranial aneurysms in patients with family history of intracerebral aneurysm is indicated
    • For ruptured intracranial aneurysm r1
      • Surgical clipping or endovascular coiling is done to reduce rate of rebleeding after aneurysmal subarachnoid hemorrhage
      • Either endovascular coiling or neurosurgical clipping can be beneficial in aneurysmal subarachnoid hemorrhage
      • Individual characteristics will determine the best means of repair
    Contraindications
    • For unruptured aneurysm
      • Patient older than 60 years, history of ischemic cerebrovascular disease, mass effect of aneurysm, and medical comorbidities are associated with increased operative risk and so are relative contraindications r4
    Complications
    • Failure of clipping, bleeding or rebleeding of aneurysm, seizures, stroke, infection, impaired cognition, and decreased independence with activities of daily living
    Endovascular coiling r4c133
    General explanation
    • Coil is placed in neck of the aneurysm via microcatheter r10
    • Coil causes local thrombosis and isolation of the aneurysm from the parent artery
    Indication
    • For unruptured aneurysm
      • Consider patient age; aneurysm location, size, shape, risk of rupture; presence of symptoms; and medical comorbidities when endovascular coiling for an unruptured intracranial aneurysm is being considered r4
      • Preferred for aneurysm in posterior circulation, size greater than 5 mm, and other aneurysm characteristics that may favor endovascular coiling over clipping r4r10
      • Preferred over clipping in patients older than 70 years and those with medical comorbidities r10
      • In the absence of prohibitive comorbidities, offer treatment to patients with unruptured intracranial aneurysm who have had enlargement documented during follow-up r4
      • Treatment of unruptured intracranial aneurysms in patients with family history of intracerebral aneurysm is indicated r4
    • For ruptured aneurysm r1
      • Surgical clipping or endovascular coiling is done to reduce rate of rebleeding after aneurysmal subarachnoid hemorrhage
      • Individual characteristics will determine the best means of repair
      • Aneurysms treated with endovascular coiling are more likely to rebleed than those treated with surgical clipping
    Contraindications
    • Prior ischemic cerebrovascular disease, mass effect of aneurysm, and medical comorbidities are associated with increased operative risk and therefore are relative contraindications
    Complications
    • Failure of aneurysm occlusion, bleeding or rebleeding of aneurysm, seizures, stroke, infection, impaired cognition, and decreased independence with activities of daily living r10
    • Complications occur less frequently after coil insertion than with clipping r10
    Ventricular drain placement r46c134
    General explanation
    • Placement of drain in lateral ventricle with external drainage
    Indication
    • Elevated intracranial pressure secondary to acute hydrocephalus with decreased level of consciousness r2
    Contraindications
    • Coagulopathy, thrombocytopenia
    Complications
    • Bleeding, infection

    Comorbidities c135

    Special populations

    • Pediatric patients
      • Cerebral aneurysms (unruptured or ruptured) are rare and poorly understood in this population r47
      • Location, size, shape, presentation, and cause of pediatric brain aneurysms are different than those in adults r47

    Monitoring

    • Follow-up imaging of untreated, unruptured cerebral aneurysms
      • Typically incidental finding on vascular imaging
      • Best followed up using the same vascular imaging modality (CT angiography, magnetic resonance angiography, digital subtraction angiography) with which the initial diagnosis was made r3c136c137c138
        • If aneurysm appears stable after repeated CT angiography or digital subtraction angiography studies, consider using magnetic resonance angiography for further follow-up to reduce ionizing radiation dose to the patient
      • Optimal recommended interval and duration of follow-up is uncertain. Imaging 6 to 12 months after initial discovery of aneurysm, with subsequent follow-up every 1 to 2 years, may be reasonable r4r43
        • Most experts favor lifelong surveillance r43
      • Follow-up imaging demonstrating aneurysm growth, aneurysm irregularity, or enhancement of the aneurysm wall suggests increased risk for rupture and treatment may be warranted r48
    • Follow-up imaging of previously treated cerebral aneurysms r4
      • Obtain digital subtraction angiogram as preferred option for follow-up of treated aneurysms c139c140
        • Magnetic resonance angiogram is a noninvasive option for follow-up of treated aneurysms
      • Imaging after surgical intervention to document aneurysm obliteration is recommended r1
      • Long-term follow-up imaging after surgical intervention to monitor for aneurysm recurrence and new aneurysm formation
        • Long-term follow-up may be particularly important for incompletely obliterated aneurysm
        • There are no guideline recommendations for frequency of monitoring after surgical intervention

    Complications and Prognosis

    Complications

    • For unruptured aneurysm
      • Growth that causes symptomatic impingement on cerebral structures or cranial nerves c141
      • Rupture c142
    • For ruptured aneurysm
      • Rebleeding c143
        • Risk of rebleeding is maximal in the first 2 to 12 hours (4%-13.6% within the first 24 hours) r1
          • Early rebleeding is associated with worse outcome than later rebleeding r1
        • Risk of late rebleeding after aneurysm repair is 2.9% after endovascular repair and 0.9% after clipping r1r49
        • Incomplete initial obliteration of the aneurysm is a risk factor for recurrent hemorrhage r1
      • Hyponatremia r50c144
        • Common after a subarachnoid hemorrhage with 10% to 30% incidence r1
        • 73% of hyponatremia cases occur within the first 3 days after subarachnoid hemorrhage, with 12% by day 7 and 14% after 1 week r51
      • Angiographic vasospasm and delayed cerebral ischemia r52r53c145
        • Vasospasm results in decreased blood flow and ischemia
        • Neurologic deficits develop gradually over hours, and are usually characterized by impaired orientation and decreased level of consciousness preceding focal deficits
        • Occurs commonly after acute subarachnoid hemorrhage, most often 7 to 10 days after aneurysm rupture, and resolves spontaneously after 21 days r1
        • Large artery narrowing seen by angiography results in ischemic neurologic symptoms in 50% of cases r1
      • Seizures c146
        • Occur in approximately 6% to 18% of ruptured aneurysm cases r1
        • Delayed seizures occur in 3% to 7% of cases r1
      • Hydrocephalus r11r54c147
        • Acute hydrocephalus can occur in approximately 20% to 67% of patients within 3 days after a ruptured aneurysm r11r54
        • Subacute hydrocephalus can occur within the first 7 days after a ruptured aneurysm r11
        • Delayed hydrocephalus can occur 10 to 30 days after a ruptured aneurysm r11
      • Neurogenic pulmonary edema results in increased interstitial and alveolar fluid in the setting of an acute central nervous system injury, including subarachnoid hemorrhage r55c148
      • Anemia can occur in 18% of cases after aneurysmal subarachnoid hemorrhage r56c149
      • Heparin-induced thrombocytopenia occurs in 5% of patients with aneurysmal subarachnoid hemorrhage r1c150
        • Does not appear to be related to the use of heparin for deep venous thrombosis prophylaxis but rather to its use in multiple angiographic procedures
      • Deep vein thrombosis occurs in approximately 10% of cases with aneurysmal subarachnoid hemorrhage r57c151

    Prognosis

    • Unruptured cerebral aneurysms can go unnoticed throughout a person's life
      • Prevalence of unruptured intracerebral aneurysms is 2.8% r18
      • Estimated rate of rupture of intracerebral aneurysm is 0.25% per year for the general population with aneurysm r4
    • Ruptured cerebral aneurysms can lead to stroke, brain damage, or death r5
      • Cumulative mortality associated with subarachnoid hemorrhage is as follows for patients receiving medical care: r5
        • 25% to 30% after 1 day
        • 40% to 45% after 1 week
        • 50% to 60% after 1 month
        • 55% to 60% after 6 months
        • 65% after 1 year
        • 65% to 70% after 5 years
      • 12% of patients will die before getting medical attention r5
      • Including patients who die before medical attention, 43% of all subarachnoid hemorrhage patients die without recovering from the initial bleeding r5
      • Of patients who recover from an untreated ruptured aneurysm, one-third will die within 6 months owing to recurrent bleeding r5
        • Cumulative risk of rebleeding is 50% 6 months after rupture
      • Despite treatment, ruptured aneurysms are associated with fatality in one-third of cases and with severe disability in one-sixth of cases r5
      • Patients who are treated have a varied recovery period ranging from weeks to months, often with permanent neurologic impairment

    Screening and Prevention

    Screening

    At-risk populations r4

    • Noninvasive screening for intracerebral aneurysm is beneficial only in populations with a higher expected prevalence and higher risk of rupture
    • Offer screening by CT angiography or magnetic resonance angiography to patients with 2 or more family members with history of intracerebral aneurysm or subarachnoid hemorrhage r3r4r8
    • Consider offering screening in those with a history of autosomal dominant polycystic kidney disease, fibromuscular dysplasia, aortic aneurysms, coarctation of the aorta, and microcephalic osteodysplastic primordial dwarfism, particularly those with a positive family history r4r8

    Screening tests r4

    • Magnetic resonance angiography c152
    • CT angiography c153

    Prevention

    • Preventive measures to decrease risk of aneurysm rupture leading to subarachnoid hemorrhage include the following: r1r4
      • Avoidance of tobacco c154
      • Avoidance of alcohol abuse c155
      • Treatment of hypertension may provide some decreased risk of aneurysm growth and rupture c156
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