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    Cerebral aneurysm

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    Feb.26.2024

    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; and focal neurologic deficits (including cranial nerve palsies)
      • Patients with an unruptured intracranial aneurysm are frequently asymptomatic
    • Noncontrast head CT is first line diagnostic test when a ruptured aneurysm is suspected, followed by lumbar puncture to assess for xanthochromia if CT findings are inconclusive
      • After confirmation of hemorrhage, obtain further imaging 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 r1r2
      • Screening for intracerebral aneurysm is beneficial only in populations with a higher expected prevalence and higher risk of rupture
    • A ruptured intracranial aneurysm requires immediate attention, and treatment can involve surgical, endovascular, and drug therapies, including control of hypertension, hyponatremia, seizures, and vasospasm, as well as correction of coagulation factors and general medical support r3
    • 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 r1
    • Main complications of ruptured aneurysm include rebleeding, delayed cerebral ischemia from vasospasm, and hydrocephalus
    • Aneurysmal subarachnoid hemorrhage has a high early mortality rate, with approximately 23% of patients dying before being evaluated in the hospital and a 30-day case fatality rate of approximately 20% for those hospitalized r4

    Urgent Action

    • Aneurysmal subarachnoid hemorrhage is a medical emergency requiring immediate care and evaluation
    • Transfer to specialized care and/or a specialized facility on admission to the emergency department
    • Obtain emergent multidisciplinary consultation (neurosurgeon and interventional radiologist), as repair, if indicated, should be performed as soon as possible
    • Monitor all patients for clinical status using a validated assessment scale
    • 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 headaches occur within 2 to 8 weeks of rupture r5
    • Imaging findings, including results of 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 r6
      • Ruptured cerebral aneurysms can lead to stroke, brain damage, or death r7
    • 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 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: smaller 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 r1c1
      • Aneurysms smaller than 7 mm in diameter are most frequently detected overall but are unlikely to cause symptoms r1
      • Unruptured intracranial aneurysm can be found incidentally during evaluation for unrelated disorders/symptoms (eg, hemorrhage from another intracranial aneurysm, headache, stroke, transient ischemic attack) r13
      • Most common symptoms of 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)
      • Severe headache ("worst headache of my life") c7
        • "Thunderclap" headache (extremely sudden and immediately reaching maximum intensity) r14c8
        • Preceded by a warning or sentinel headache, caused by aneurysm leaking before frank rupture occurs, in 10% to 43% of cases r5r14c9
          • Majority of these severe headaches occur within 2 to 8 weeks of rupture
      • Headache may be accompanied by one or more signs and symptoms including:
        • Nausea and/or vomiting c10c11
        • Loss of consciousness; may progress to coma c12c13
        • Stiff neck c14
        • 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 the nose, sexual activity, defecation, vigorous exercise, or anger r8

    Physical examination

    • Unruptured aneurysm
      • Most often asymptomatic without abnormal physical findings r1
      • Unruptured aneurysm may cause a mass effect, presenting as one or more of the following: r1r10
        • 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 one or more of the following:
        • Altered consciousness (up to loss of consciousness) c25c26
          • Evaluation includes a standardized severity score such as: r3r14
            • Intracerebral Hemorrhage Score
            • NIH Stroke Scale r15
            • Hunt and Hess Scale
            • Ottawa Subarachnoid Hemorrhage Rule
        • 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 r17c34
          • Typically within first 24 hours. More commonly associated with intracerebral hemorrhage, hypertension, and aneurysms of middle- and anterior-communicating arteries

    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 fifth and sixth decades of life r1r8c36c37c38c39c40c41
    • Growth rate of existing intracranial aneurysm is faster in younger people r1c42c43c44c45c46
    Sex
    • Overall incidence is higher in females, with 3 to 1 female to male ratio r1r10c47c48
      • Males and females are equally affected before age of 40 years r8
    • Relative risk for growth is higher in females by a factor of 2.3 r1r18c49c50
    Genetics
    • Autosomal dominant inheritance pattern occurs in some patients r1c51
    • Several genes or chromosomal regions have been identified in both familial and sporadic cases of intracranial aneurysm r1r19
    • Incidence is approximately 7% to 20% in people with family members who have had an aneurysm r1c52
    Ethnicity/race
    • In the United States, American Indian, Alaska Native, Asian Pacific Islander, and Black populations have a higher mortality rate from ruptured aneurysms than the White population r1c53c54c55c56c57
    • Patients in Japan and Finland have an increased risk for aneurysm rupture; however, it is unclear whether this is attributable to ethnicity or a result of exposure to environmental risk factors in those geographic regions r8r20c58c59
    Other risk factors/associations r1
    • For development of intracranial aneurysm
      • Cigarette smoking c60c61
        • 36% to 61% of patients with an unruptured intracranial aneurysm are current smokers, and 19% to 33% are former smokers r1
      • Hypertension c62
        • Hypertension may be a risk factor for aneurysm development; however, there is little evidence that control of hypertension reduces risk of aneurysm development r1
      • Alcohol use c63
        • Excessive alcohol use (more than 150 g/week) increases risk of aneurysm formation independent of sex, age, cigarette smoking, and history of hypertension r7
      • Disorders associated with increased risk for aneurysm development, although together they represent less than 10% of patients presenting with an unruptured aneurysm, are as follows: r1
        • Polycystic kidney disease (3- to 14-fold increased risk) r1c64
        • 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 r1
        • Location r21r22
          • Aneurysms in posterior circulation are more likely to grow c86
        • Shape r21
          • Aneurysms with lobulations are more likely to grow c87
        • Size r23
          • Aneurysms that are larger at diagnosis are more likely to grow than smaller aneurysms c88
        • Multiple aneurysms c89
      • Cigarette smoking r1c90
      • Hypertension r1c91
      • Alcohol use r24c92
      • History of stroke or transient ischemic attack c93c94
    • For rupture of intracranial aneurysm/SAH (subarachnoid hemorrhage)
      • Cigarette smoking r25c95
        • Relative risk for SAH for current smokers is 2.2 to 3.1 compared with that for nonsmokers r7
        • 40% of aneurysms with SAH can be attributed to cigarette smoking r7
      • Hypertension r1c96
        • May be a risk factor for aneurysm rupture with an odds ratio of 1.5 to 2.4 r26
      • Alcohol use c97
        • Excessive alcohol use (more than 150 g/week) is a risk factor for aneurysm rupture r7
      • Illicit drug use c98c99
        • Cocaine use is associated with hemorrhage of intracranial aneurysms at younger age and with smaller aneurysms compared with overall population with hemorrhage r27r28
          • Mean age at rupture is 31 years r28

    Diagnostic Procedures

    Primary diagnostic tools

    • Suspected ruptured cerebral aneurysm (acute SAH [subarachnoid hemorrhage]) based on the following: c100
      • History of sudden-onset severe headache, maximal at onset, and dissimilar to previous headaches ("thunderclap" headache) r3r29
      • Physical findings such as altered/deteriorating level of consciousness, focal neurologic deficits, nuchal rigidity r16
      • Consider using the Ottawa Subarachnoid Hemorrhage Rule for patients with acute onset of severe headache and no new neurologic deficits to identify those who require evaluation for SAH r14
        • Subset of patients who meet none of the Ottawa Subarachnoid Hemorrhage Rule criteria are unlikely to have aneurysmal SAH and can therefore avoid imaging and additional workup
    • Perform urgent noncontrast head CT or MRI as initial imaging modality for patients with suspected SAH to establish presence and size of intracerebral hemorrhage r2r3r14c101
      • CT is most widely used modality r3
        • MRI with echo-planar gradient echo or susceptibility-weighted sequences is also highly accurate at detecting acute intracerebral hemorrhage r3
      • Serial CT after initial scan can be useful to evaluate for development of hemorrhage expansion, hydrocephalus, or perihematomal edema r3
      • Negative noncontrast head CT is likely sufficient to exclude SAH in patients presenting within 6 hours of headache onset who have no new neurologic deficits r14
    • Perform lumbar puncture to evaluate for xanthochromia if imaging study results are negative and patient has typical severe headache with onset more than 6 hours prior or a new neurologic deficit r14c102
      • Absence of xanthochromia on cerebrospinal fluid analysis excludes SAH
      • If lumbar puncture is not feasible, patient refuses it, or results are equivocal, can consider CT angiography after negative imaging study r29r30c103
        • A drawback of vascular imaging in this setting is discovery of aneurysms that are not the cause of the headache r29
    • After confirming hemorrhage, obtain intracranial vascular imaging to detect and characterize vascular abnormalities such as ruptured cerebral aneurysms (cause of 80%-90% of nontraumatic hemorrhages) that require prompt intervention r2r17
      • CT angiography is commonly performed, as it is widely available and noninvasive r14
        • Lower sensitivity for detecting small aneurysms (smaller than 3 mm) r2
        • Negative predictive value in this setting is poor r2
          • For patients with negative CT angiography study results, performing catheter angiography can result in detection of causative lesion in 15% of those with diffuse SAH and 9% of those with sulcal SAH r2
      • Magnetic resonance angiography has sensitivity similar to that of CT angiography, does not require IV contrast, and may be useful for certain patients (eg, those with renal dysfunction or iodine allergy) c104
      • Catheter intra-arterial digital subtraction angiography is the gold standard diagnostic tool for detecting macrovascular causes of intracerebral hemorrhage such as aneurysms r2r31
        • Best able to recognize small aneurysms
          • Small aneurysms (less than 3 mm in diameter) account for almost one-third of ruptured aneurysms r2
        • Indicated for evaluating diffuse SAH, regardless of CT angiography results
        • Indicated to exclude aneurysm if initial noninvasive imaging study is negative or inconclusive (ie, owing to small aneurysm size, aneurysm thrombosis, local vasospasm, incomplete study): r2r14
          • 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 symptoms or symptoms related to increasing size of the aneurysm compressing nearby brain structures r1
        • History and physical examination findings may suggest diagnosis
      • Imaging studies confirm diagnosis
        • Noninvasive CT angiography and magnetic resonance angiography are preferred for identification of unruptured intracranial aneurysm r1r2
          • 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 for some patients (eg, those with obesity or claustrophobia or those who have metal implants)
        • Digital subtraction angiography may be considered over noninvasive imaging if surgical or endovascular treatment is being considered r1

    Laboratory

    • Cerebrospinal fluid analysis r32c105
      • Diagnosis of SAH 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 SAH
          • Takes several hours to appear after bleeding begins (20% of patients at 6 hours) and can last for up to 2 weeks r30
        • Spectrophotometric analysis of centrifuged cerebrospinal fluid is more accurate than visual inspection in detecting xanthochromia r33

    Imaging

    • Imaging studies
      • Noncontrast CT c106
        • Initial imaging test of choice to evaluate for suspected SAH/ruptured intracerebral aneurysm r2r17
          • 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 r17
        • 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) r1c107
        • 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 r1
          • For patients with renal insufficiency or Ehlers-Danlos syndrome, risks with catheter angiography are higher; consider noninvasive imaging instead
        • Gold standard for diagnosis and localization of aneurysm in SAH r2r17
          • Able to identify very small aneurysms (smaller than 3 mm) and lesions (eg, perforating arteries in very small vessels) r1
          • Has sensitivity above 90% (falls to slightly greater than 80% in setting of acute SAH) r2
        • 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 for patients who have had previous aneurysm treatments) r2
          • Can be more useful than noninvasive imaging if surgical or endovascular treatment is being considered r1
        • Highest diagnostic yield as an adjunct or alternative to CT- or MRI–based vascular imaging in the following groups: r3
          • Patients younger than 70 years with lobar intracerebral hemorrhage
          • Patients younger than 45 years with deep or posterior fossa intracerebral hemorrhage
          • Patients aged 45 to 70 years with deep or posterior fossa intracerebral hemorrhage and absence of both history of hypertension and signs of small vessel disease on imaging
          • Patients with intracerebral hemorrhage and CT or MRI evidence of a macrovascular lesion
          • Patients with primary intraventricular hemorrhage
      • CT angiography c108
        • Advantages include rapid image acquisition, low motion susceptibility, availability, and relatively high spatial resolution r2
        • 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 setting of diffuse SAH r2
        • Importantly, sensitivity for smaller aneurysms (less than 3 mm in diameter) is much lower (around 55%); these can account for almost one-third of ruptured aneurysms r2
          • CT angiography may not accurately depict small vessel anatomy, which can be an important determinant of treatment decisions r34
        • Indications include
          • After nondiagnostic noncontrast head CT result, consider excluding aneurysmal SAH when lumbar puncture is difficult or not feasible, refused by patient, or results are equivocal r17r29
          • Alternative (second line) to catheter angiography to detect and characterize ruptured cerebral aneurysm r2
          • Screening tool for unruptured aneurysms for at-risk populations r1r2
      • Magnetic resonance angiography c109
        • 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 adherence, and longer study time r17
        • Comparable overall sensitivity to that of CT angiography in detection of intracranial aneurysms r2
          • Magnetic resonance angiography likely has slightly inferior specificity
          • Similar to CT angiography, shown to have difficulty with aneurysms smaller than 3 mm r2
          • No significant differences in 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 r2
          • Screening tool for unruptured aneurysms in at-risk populations r1r2
      • MRI c110
        • MRI with echo-planar gradient echo or susceptibility-weighted sequences is highly accurate at detecting acute intracerebral hemorrhage r3
        • MRI (fluid-attenuated inversion recovery, proton density, diffusion-weighted imaging, gradient echo sequences) may be reasonable for diagnosis of SAH in patients with a nondiagnostic CT scan result, although a negative result does not obviate need for cerebrospinal fluid analysis r17

    Procedures

    Lumbar puncture c111
    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 SAH (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 observed at least 12 hours after SAH r7r17
    • Within first 6 to 12 hours, 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 r33

    Other diagnostic tools

    • Ottawa Subarachnoid Hemorrhage Rule r14
      • Applies to alert patients older than 15 years with new severe nontraumatic headache that reached maximum intensity within 1 hour and no new neurologic deficit
        • Patients require additional investigation for SAH if they meet any of the following criteria:
          • Age 40 years or older
          • Neck pain or stiffness
          • Witnessed loss of consciousness
          • Onset during exertion
          • Thunderclap headache (in which pain instantly peaks)
          • Limited neck flexion on examination
        • Patients who do not meet any of the criteria have a very low likelihood of aneurysmal SAH

    Differential Diagnosis

    Most common

    • Migraine headache r10c112d1
      • Recurrent, episodic headache attacks that may or may not be preceded by a focal neurologic symptom (aura)
      • Migraine can cause moderate to severe localized, often unilateral pain, accompanied by nausea and vomiting 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 a headache
      • Noncontrast CT scan result will be normal with migraine
    • Stroke or transient ischemic attack r1c113c114d2
      • Patient may present with transient or fixed neurologic deficit, as with intracerebral aneurysm, but usually without headache
      • CT and MRI confirm absence of SAH (subarachnoid hemorrhage) or aneurysm. MRI may show evidence of transient ischemia during a transient ischemic attack
    • Cerebral venous sinus thrombosis r35c115
      • Acute thrombosis in dural venous sinuses causes headache, abnormal vision, and other cranial neuropathies; similar to symptoms of cerebral aneurysm
      • Seizures occur in 20% to 40% of cases r35
      • Headache is present in nearly 90% of cases r35
        • A minority of patients experience a more acute presentation with thunderclap headache
      • Patients may also present with papilledema or diplopia
      • Diagnosis is based on MRI/magnetic resonance venography or CT/computed tomographic venography
        • MRI/magnetic resonance venography is the recommended noninvasive study to confirm diagnosis
      • Differentiated by imaging results consistent with thrombus
    • Meningitis r36c116d3
      • Inflammation of meninges
      • Bacterial meningitis most commonly causes vomiting, headache, and nuchal rigidity similar to symptoms of cerebral aneurysm d4
      • Differentiated by presence of fever without thunderclap headache and cerebrospinal fluid results indicating bacterial infection
    • Cerebral vasoconstriction syndrome r37r38c117
      • Condition caused by arterial constriction and dilation
      • Can mimic SAH 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

    Disposition

    Admission criteria

    Admit patients with suspected symptomatic unruptured intracranial aneurysm to the hospital for observation, diagnosis, and treatment r1

    All ruptured intracranial aneurysms require immediate transfer to the emergency department r3

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

    Recommendations for specialist referral r7

    • Transfer patients to 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 35 cases annually) r1r14

    Treatment Options

    Treatment of ruptured intracranial aneurysm

    • Definitive treatment is urgent surgical or endovascular intervention
      • Increased time to treatment is associated with increased rates of preoperative rebleeding and poor outcome r14
      • Obtain emergent multidisciplinary consultation (neurosurgeon and interventional radiologist)
      • Determine aneurysm treatment with a multidisciplinary team, considering patient's individual requirements and aneurysm characteristics
      • 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
      • Choice of intervention is determined by patient's age, comorbid conditions, aneurysm characteristics, and severity of hemorrhage and neurologic compromise r3r14
      • If patient is a candidate for repair, proceed to surgical clipping or endovascular coiling of the ruptured aneurysm as soon as possible (ideally within 24 hours) to improve outcome r3r14
        • Endovascular coiling is most common approach to repair and has highest level of evidence for benefit r31
        • Surgical clipping may be considered preferable for patients younger than 40 years owing to durability of treatment
      • For patients with aneurysms unsuitable for endovascular coiling or surgical clipping, endovascular stents or flow diverters may be reasonable; these should not be used on saccular aneurysms amenable to coiling or clipping r14
    • Placement of a ventricular drainage catheter
      • Ventricular drainage as treatment for elevated intracranial pressure secondary to hydrocephalus is recommended, especially for patients with decreased level of consciousness r3
    • Adjunctive medical therapies r17
      • Prevention of rebleeding
        • Discontinue any antithrombotic agents and urgently reverse anticoagulation with appropriate reversal agents until aneurysm is definitively repaired r14
        • Treat severe hypertension with β-blockers or calcium channel blockers: labetalol, esmolol, and nicardipine r17
          • For systolic blood pressure over 180 to 200 mm Hg and without contraindication to acute blood pressure treatment, gradually lower systolic blood pressure while strictly avoiding hypotension r3r14
            • Elevated systolic blood pressure above 160 mm Hg and increased blood pressure variability have been associated with aneurysm rebleeding r39
            • Optimal blood pressure to reduce risk of rebleeding in SAH (subarachnoid hemorrhage) has not been established; systolic blood pressure below 140 mm Hg or below 160 mm Hg has been suggested r14
            • Acute lowering of systolic blood pressure to less than 130 mm Hg in patients with intracerebral hemorrhage and elevated blood pressure is potentially harmful r3
        • Replace coagulation factors for patients with a severe coagulation factor deficiency; replace platelets for patients with severe thrombocytopenia
        • Short-term treatment with antifibrinolytic agents is not routinely recommended; does not improve rate of rebleeding or functional outcomes r39r40
          • Possible role if definitive treatment of aneurysm is delayed r14
      • Oral nimodipine r14r31r39
        • Nimodipine has been shown to reduce all-cause mortality, delayed cerebral ischemia, and cerebral vasospasm and to improve functional outcomes r41
        • Administer to all patients with acute SAH
        • There is insufficient evidence to support use of other calcium channel blockers or other routes of administration r39
      • Other adjunctive medications r41
        • Cilostazol is associated with reduction in delayed cerebral ischemia and cerebral vasospasm and improved functional outcomes; however, there is no clear guidance for or against its use
        • Other medications such as statins, endothelin-1 antagonists, magnesium, and phospholipase A2 inhibitors have uncertain effects and are not recommended r14
    • Ongoing general medical support r3r39
      • Manage patients with SAH in an ICU or dedicated stroke unit with constant hemodynamic, cardiac, and neurologic monitoring
      • Assess clinical condition initially and continuously with use of a validated scale (eg, Intracranial Hemorrhage Scale, NIH Stroke Scale, Hunt and Hess Scale)
      • Maintain oxygenation without hyperventilation and periodically assess with oximetry and measurement of arterial blood gases
      • Closely monitor fluid volume status and manage fluids to maintain euvolemia
        • Hydration with isotonic saline is preferred
      • Manage glucose level to prevent hypo- and hyperglycemia
      • Treat headache and other pain with acetaminophen and short-acting opiates
      • Treat seizures with anticonvulsants r3
        • Prophylactic administration of anticonvulsants is not recommended
      • Control fever with antipyretic medications
      • Monitor sodium level. Treat hyponatremia with infusion of 3% saline solution or fludrocortisone r42
      • Apply intermittent pneumatic compression for prevention of venous thromboembolism, beginning on day of hospital admission; pharmacologic venous thromboembolism prophylaxis can be commenced once aneurysm is definitively treated

    Treatment of an unruptured intracranial aneurysm r1r10

    • Preventive aneurysm repair eliminates risk of aneurysm rupture but carries approximately 6% to 10% risk of poor neurologic outcome. For most aneurysms, this is higher than risk of rupture
    • The decision of whether to perform preventive repair of an unruptured aneurysm should be undertaken by a multidisciplinary cerebrovascular team, taking into consideration risk factors for aneurysm rupture and risks associated with repair
    • Risk for aneurysm rupture can be predicted based on the following: r43r44
      • Aneurysm characteristics r44
        • Size (diameter, perpendicular height)
        • Shape
        • Location
        • Aneurysm to parent vessel size ratio
        • Growth on follow-up
      • Patient characteristics associated with increased risk for rupture r20
        • Presence of multiple aneurysms
        • Hypertension
        • History of SAH
        • 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 with North America and Europe) r45
    • 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 risk of aneurysm rupture r45r46r47
    • Generally, conservative management (ie, regular monitoring with imaging) is appropriate for patients with small asymptomatic aneurysms (smaller than 5-7 mm) who are not at increased risk of rupture, taking into consideration aneurysm-related symptoms, age, and comorbidities r1r48r49
      • Treat any modifiable risk factors, such as hypertension, and counsel regarding smoking cessation and reduction in heavy alcohol consumption r20
        • Daily low-dose aspirin is safe to use for patients with small unruptured aneurysms and may reduce aneurysm wall inflammation and risk of rupture r50
    • 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 r1r48
      • Many experts also endorse routine treatment of aneurysms between 5 and 7 mm in size r48
      • Optimal treatment modality for preventive repair has not been definitely established r20
        • Endovascular coiling r1r10
          • 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 for older patients or patients with comorbidities and for aneurysms involving posterior circulation r20
          • Associated with lower morbidity and mortality but higher risk of recurrence than surgical clipping r8
        • Microsurgical clipping r1r10
          • 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 r20
        • Use of endoluminal flow diversion and administration of liquid embolic agents are additional techniques in development but are not guideline recommended r1

    Drug therapy

    • Calcium channel blockers r39
      • Nicardipine c118
        • 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. Reduce to 3 mg/hour after response achieved.
      • Nimodipine c119
        • Nimodipine Oral capsule, liquid filled; Adults: 60 mg PO every 4 hours for 21 days, beginning within 96 hours of the onset of subarachnoid hemorrhage.
    • β-Blockers
      • Esmolol c120
        • 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.
      • Labetalol c121
        • 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, followed by 0.5 to 2 mg/minute continuous IV infusion, initially. Titrate dose every 15 minutes until goal blood pressure is attained. May repeat or double bolus dose after 10 minutes and before starting infusion. Max: 10 mg/minute. Max cumulative dose: 300 mg.
    • Anticonvulsants r3
      • Lorazepam c122
        • Lorazepam Solution for injection; Adults: 0.1 mg/kg/dose (Max: 4 mg/dose) IV/IM as a single dose; may repeat dose once in 5 to 15 minutes.
      • Fosphenytoin c123
        • Fosphenytoin Sodium Solution for injection; Adults: 20 mg PE/kg/dose (Max: 1,500 mg PE/dose) IV as a single dose; may administer additional 5 to 10 mg PE/kg/dose IV as a single dose after 10 minutes if needed.

    Nondrug and supportive care

    c124

    c125

    Procedures
    Microsurgical clipping r10c126
    General explanation
    • Aneurysm is dissected, and a small metallic clip is placed at neck of aneurysm to isolate it from parent blood vessel r10
    Indication
    • For unruptured intracranial aneurysm r1
      • Take into account patient age; aneurysm location, size, shape, and risk of rupture; symptoms; and medical comorbidities when considering surgical clipping for an unruptured intracranial aneurysm
      • Preferred option for younger patients (younger than 50 years), smaller aneurysms (smaller than 10 mm), aneurysms in anterior circulation, and aneurysms with shape or size making complete occlusion by endovascular coiling unlikely
      • In 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 r14
      • Surgical clipping or endovascular coiling is done to reduce rate of rebleeding after aneurysmal SAH
      • Either endovascular coiling or neurosurgical clipping can be beneficial for patients with aneurysmal SAH
      • Individual characteristics will determine best means of repair
    Contraindications
    • For unruptured aneurysm
      • Age greater 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 r1
    Complications
    • Failure of clipping, bleeding or rebleeding of aneurysm, seizures, stroke, infection, impaired cognition, and decreased independence in activities of daily living
    Endovascular coiling r1c127
    General explanation
    • Coil is placed in neck of aneurysm via microcatheter r10
    • Coil causes local thrombosis and isolation of aneurysm from 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 r1
      • Preferred for aneurysm in posterior circulation, size greater than 5 mm, and other aneurysm characteristics that may favor endovascular coiling over clipping r1r10
      • Preferred over clipping for patients older than 70 years and those with medical comorbidities r10
      • In absence of prohibitive comorbidities, offer treatment to patients with unruptured intracranial aneurysm who have had enlargement documented during follow-up r1
      • Treatment of unruptured intracranial aneurysms in patients with family history of intracerebral aneurysm is indicated r1
    • For ruptured aneurysm r14
      • Surgical clipping or endovascular coiling is done to reduce risk of rebleeding after aneurysmal SAH
      • Individual characteristics will determine 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 in activities of daily living r10
    • Complications occur less frequently after coil insertion than after clipping r10
    Ventricular drain placement r51c128
    General explanation
    • Placement of drain in lateral ventricle with external drainage
    Indication
    • Elevated intracranial pressure secondary to acute hydrocephalus with decreased level of consciousness r3
    Contraindications
    • Coagulopathy, thrombocytopenia
    Complications
    • Bleeding, infection

    Comorbidities c129

    Special populations

    • Pediatric patients
      • Cerebral aneurysms (unruptured or ruptured) are rare and poorly understood in this population r52
      • Location, size, shape, presentation, and cause of brain aneurysms in pediatric patients are different than those in adults r52

    Monitoring

    • Follow-up imaging of untreated, unruptured cerebral aneurysms
      • Typically identified as incidental finding on vascular imaging
      • Vascular imaging surveillance is recommended owing to potential for growth and rupture of untreated and unruptured aneurysms r53
      • CT angiography and magnetic resonance angiography are most appropriate modalities; CT angiography is less sensitive at detecting aneurysms smaller than 3 mm and those adjacent to osseous structures r53c130c131c132
      • Optimal recommended interval and duration of follow-up are uncertain. Imaging 6 to 12 months after initial discovery of aneurysm, with subsequent follow-up every 1 to 2 years, may be reasonable r1r49
        • Most experts favor lifelong surveillance r49
      • Follow-up imaging demonstrating aneurysm growth, aneurysm irregularity, or enhancement of aneurysm wall suggests increased risk for rupture; treatment may be warranted r54
    • Follow-up imaging of previously treated cerebral aneurysms r1
      • Long-term surveillance imaging is recommended after treatment to monitor for refilling of treated aneurysm, integrity of parent vessel, and development of new aneurysms r17r53
        • There are no guideline recommendations for frequency of monitoring after surgical intervention
      • Cervicocerebral arteriography is the reference standard imaging examination r53c133c134
      • Magnetic resonance angiography is the most commonly used noninvasive examination r53
        • Magnetic resonance angiography or CT angiography may be used; however, presence of metallic coils and other endovascular devices may limit utility of these modalities

    Complications and Prognosis

    Complications

    • For unruptured aneurysm
      • Growth that causes symptomatic impingement on cerebral structures or cranial nerves c135
      • Rupture c136
    • For ruptured aneurysm
      • Early brain injury r55
        • Global cerebral edema, metabolic distress, and inflammation occurring during first 72 hours after aneurysmal rupture are common
      • Rebleeding c137
        • Risk of rebleeding is maximal in first 2 to 12 hours (4%-13.6% within first 24 hours) r17
          • Early rebleeding is associated with worse outcome than later rebleeding
        • Risk of late rebleeding after aneurysm repair is 2.9% after endovascular repair and 0.9% after clipping r56
      • Hydrocephalus and elevated intracranial pressure r11r55r57c138
        • Hydrocephalus occurs in 12% to 31% of patients
      • Delayed cerebral ischemia r58r59c139
        • Delayed cerebral ischemia occurs in approximately 30% of patients, most often 4 to 14 days after aneurysm rupture r14
        • Primary cause is large vessel vasospasm resulting in decreased blood flow and ischemia r55
      • Hyponatremia r60c140
        • Common after a SAH (subarachnoid hemorrhage)
        • 73% of hyponatremia cases occur within first 3 days after SAH, with 12% by day 7 and 14% after 1 week r61
      • Seizures c141
        • Occur in approximately 7% to 15% of ruptured aneurysm cases r14
        • Onset may be at time of hemorrhage, during hospitalization, or later as a long-term consequence r55
        • Increased incidence among patients with surgically clipped aneurysms, high-grade aneurysms, location of aneurysm in middle cerebral artery, and hydrocephalus r14
      • Cardiac dysfunction
        • Includes cardiac biomarker, electrocardiographic, or cardiac wall-motion abnormalities r55
        • Develops in about 20% of patients after SAH r62
      • Anemia can occur in 18% of cases after aneurysmal SAH r63c142
      • Neurogenic pulmonary edema results in increased interstitial and alveolar fluid in setting of an acute central nervous system injury, including SAH r64c143
      • Deep vein thrombosis occurs in 10% of cases with aneurysmal SAH r65c144

    Prognosis

    • Unruptured cerebral aneurysms can go unnoticed throughout a person's life
      • Prevalence of unruptured intracerebral aneurysms is 2.8% r19
      • Estimated rate of rupture of intracerebral aneurysm is 0.25% per year for the general population with aneurysm r1
    • Ruptured cerebral aneurysms can lead to stroke, brain damage, or death r7
      • Aneurysmal SAH (subarachnoid hemorrhage) has a high early mortality rate, with approximately 23% of patients dying before being evaluated in the hospital r4
        • Among hospitalized patients, case fatality rate is approximately 20% at 30 days r4
      • Late mortality is increased among SAH survivors compared with the general population: a Swiss national registry showed a mortality rate of 22% at 1 year r66
      • Patients who are treated have a varied recovery period ranging from weeks to months, often with permanent neurologic impairment
        • Up to one-third of patients report diminished quality of life, attentional deficits, cognitive impairment, depression, and reduced independence in activities of daily living r55
        • In a Swiss registry, almost 60% of patients who survived SAH were living independently at 1-year follow-up r66
        • Endovascular coiling was associated with better health-related quality of life compared with neurosurgical clipping r67

    Screening and Prevention

    Screening

    At-risk populations r1

    • 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 r1r2r8
    • Consider offering screening to 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 r1r8

    Screening tests r1

    • Magnetic resonance angiography c145
    • CT angiography c146

    Prevention

    • Preventive measures to decrease risk of aneurysm rupture leading to subarachnoid hemorrhage include the following: r1
      • Avoidance of tobacco r25c147
      • Avoidance of excessive alcohol consumption c148
      • Treatment of hypertension; may provide some decreased risk of aneurysm growth and rupture c149
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