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Cerebral aneurysm

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Synopsis
Terminology
Diagnosis
Treatment
Complications and Prognosis
Screening and Prevention

May.12.2023

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 ^r1
- 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 ^r2^r3
- 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 ^r1^r4
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 ^r2
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
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 occur within 2 to 8 weeks of the rupture ^r1^r6
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: 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 ^r2^c1
- Aneurysms smaller than 7 mm in diameter are the most frequently detected overall but are unlikely to cause symptoms ^r2
- 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) ^c3^c4^c5
  - 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%) ^r1^c7
  - 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 ^r1^r6^c9
    - 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%) ^r1^c10^c11
  - Loss of consciousness (53%); may progress to coma ^r1^c12^c13
  - Stiff neck (35%) ^r1^c14
  - Diplopia or vision loss ^c15^c16
  - 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 ^r2
- Unruptured aneurysm may cause a mass effect, presenting as 1 or more of the following: ^r2^r10
  - Cranial nerve palsy (most commonly a third nerve palsy) and/or unilaterally dilated pupil ^c18^c19^c20
  - Cerebellar signs ^c21
  - Syncope ^c22
  - Other focal neurologic findings, including stroke ^c23
  - Neurologic findings without rupture may occur in 11% of patients ^r13^c24
Ruptured intracranial aneurysm (subarachnoid hemorrhage)
- May present with 1 or more of the following:
  - Altered consciousness (up to loss of consciousness) ^c25^c26
    - Evaluation includes a standardized severity score such as: ^r1^r4
      - Intracerebral Hemorrhage Score
      - NIH Stroke Scale ^r14
      - Hunt and Hess Scale
  - Focal neurologic findings ^r15
    - Cranial nerve palsy and/or unilaterally dilated pupil ^c27^c28
    - Cerebellar signs ^c29
    - Syncope ^c30
    - Other focal neurologic findings, including stroke ^c31
  - Constricted pupils ^r15^c32
  - Nuchal rigidity ^r15^c33
  - Seizures may occur in up to 20% of patients ^r1^c34
    - 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 ^r2^r8^c36^c37^c38^c39^c40^c41
Growth rate of existing intracranial aneurysm is faster in younger people ^r2^c42^c43^c44^c45^c46

Sex

Overall incidence is higher in women, with 3 to 1 female to male ratio ^r2^r10^c47^c48
- 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 ^r2^r16^c49^c50

Genetics

Autosomal dominant inheritance pattern occurs in some patients ^r2^c51
Several genes or chromosomal regions have been identified in both familial and sporadic cases of intracranial aneurysm ^r2^r17
Incidence is approximately 7% to 20% in people with family members who have had an aneurysm ^r2^c52

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 ^r2^c53^c54^c55^c56^c57
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 ^r8^r18^c58^c59

Other risk factors/associations ^r2

For development of intracranial aneurysm
- Cigarette smoking ^c60^c61
  - 36% to 61% of patients with unruptured intracranial aneurysm are current smokers, and 19% to 33% are former smokers ^r2
- 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 ^r2
- 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: ^r2
  - Polycystic kidney disease (3- to 14-fold increased risk) ^r2^c64
  - Connective tissue and skin disorders, including Marfan syndrome, pseudoxanthoma elasticum, type IV Ehlers-Danlos syndrome, and fibromuscular dysplasia ^c65^c66^c67^c68^c69^c70
  - Vascular anomalies, including coarctation of the aorta, bicuspid aortic valve, and intracranial arteriovenous malformations ^c71^c72^c73^c74
  - Enzyme deficiencies including α1-antitrypsin deficiency and α-glucosidase deficiency ^c75^c76^c77
  - Hereditary hemorrhagic telangiectasia ^c78
  - Neurocutaneous disorders, including neurofibromatosis type 1, tuberous sclerosis, and pheochromocytoma ^c79^c80^c81^c82
  - Dysmorphic disorders, including Noonan syndrome and microcephalic osteodysplastic primordial dwarfism ^c83^c84
  - Klinefelter syndrome ^c85
For growth of existing intracranial aneurysm
- Characteristics of aneurysm ^r2
  - Location ^r19^r20
    - Aneurysms in the posterior circulation are more likely to grow ^c86
  - Shape ^r20
    - Aneurysms with lobulations are more likely to grow ^c87
  - Size ^r21
    - Aneurysms that are larger at diagnosis are more likely to grow than smaller aneurysms ^c88
  - Multiple aneurysms ^c89
- Cigarette smoking ^r2^c90
- Hypertension ^r2^c91
- Alcohol use ^r22^c92
- History of stroke or transient ischemic attack ^c93^c94
For rupture of intracranial aneurysm/subarachnoid hemorrhage
- Cigarette smoking ^r23^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 ^r2^c96
  - 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 ^c98^c99
  - Cocaine use is associated with hemorrhage of intracranial aneurysms at younger age and with smaller aneurysm than the overall population with hemorrhage ^r25^r26
    - 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 ('thunderclap' headache) ^r4^r27
- Physical findings, particularly: ^r15
  - Altered/deteriorating level of consciousness
  - Focal neurologic findings
  - Nuchal rigidity
- Perform urgent noncontrast head CT or MRI as initial imaging modality to establish presence and size of intracerebral hemorrhage ^r1^r3^r4^c101
  - CT is the most widely used modality ^r4
    - Serial CT after the initial scan can be useful to evaluate for development of hemorrhage expansion, hydrocephalus, or perihematomal edema ^r4
  - MRI with echo-planar gradient echo or susceptibility-weighted sequences is also highly accurate at detecting acute intracerebral hemorrhage ^r4
- After confirming hemorrhage, obtain intracranial vascular imaging to detect and characterize vascular abnormalities such ruptured cerebral aneurysms (cause of 80%-90% of nontraumatic hemorrhage) that require prompt intervention ^r1^r3
  - Can include catheter angiography, CT angiography, or magnetic resonance angiography ^c102
    - Catheter intra-arterial digital subtraction angiography is the gold standard diagnostic tool for detecting macrovascular causes of intracerebral hemorrhage such as aneurysms ^r3^r28
      - 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
- If imaging study results are negative, perform lumbar puncture for cerebrospinal fluid analysis to detect xanthochromia and confirm subarachnoid hemorrhage ^r1^c103
  - 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 ^r1^r27^r29^c104
      - 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 ^r1^c105
      - A negative result does not eliminate the need for cerebrospinal fluid analysis
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 ^r2
  - 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 ^r2^r3
    - 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 ^r2

Laboratory

Cerebrospinal fluid analysis ^r30^c106
- 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 ^r29
  - 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 ^r1^r3
    - 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) ^r2^c108
  - 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 ^r2
    - In 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 subarachnoid hemorrhage ^r1^r3
    - Able to identify very small aneurysms (smaller than 3 mm) and lesions (eg, perforating arteries in very small vessels) ^r2
    - 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 ^r2
  - Highest diagnostic yield as an adjunct or alternative to CT- or magnetic resonance–based vascular imaging in the following groups: ^r4
    - 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 the absence of both history of hypertension and signs of small vessel disease on imaging
    - Patients with intracerebral hemorrhage with CT or magnetic resonance evidence of a macrovascular lesion
    - Patients with primary intraventricular hemorrhage
- CT angiography ^c109
  - Advantages include rapid image acquisition, low motion susceptibility, availability, and relatively high spatial 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
    - After 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 ^r1^r27
    - Alternative (second line) to catheter angiography to detect and characterize ruptured cerebral aneurysm ^r3
    - Screening tool for unruptured aneurysms for at-risk populations ^r2^r3
- 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 ^r2^r3
- MRI ^c111
  - MRI with echo-planar gradient echo or susceptibility-weighted sequences is highly accurate at detecting acute intracerebral hemorrhage ^r4
  - 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

Procedures

Lumbar puncture ^c112

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 ^r1^r5
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 ^r10^c113^d1
- 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 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 ^r2^c114^c115^d2
- 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 ^r33^c116
- 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 ^r34^c117^d3
- Inflammation of the meninges
- 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 ^r35^r36^c118
- 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

Disposition

Admission criteria

Admit patients with suspected symptomatic unruptured intracranial aneurysm to the hospital for observation, diagnosis, and treatment ^r2

All ruptured intracranial aneurysms require immediate transfer to the emergency department ^r4

A multidisciplinary team determines whether a patient is a candidate for transfer to a stroke unit or to 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 ^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) ^r1^r2

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 ^r1
- Choice of intervention is determined by patient's age, comorbid conditions, aneurysm characteristics, and severity of hemorrhage and neurologic compromise ^r1^r4
- 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 ^r1^r4
  - Endovascular coiling is the most common approach to repair and has the highest level of evidence for benefit ^r28
- 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 ^r4
Use adjunctive medical therapies to prevent rebleeding ^r1
- 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 ^r1^r4
    - Optimal blood pressure to reduce risk of rebleeding in subarachnoid hemorrhage has not been established ^r1
    - Acute lowering of systolic blood pressure to less than 130 mm Hg in patients with intracerebral hemorrhage and elevated blood pressure is potentially harmful ^r4
- 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 ^r28
Treat seizures with anticonvulsants ^r4
- Seizure prophylaxis with anticonvulsants is not recommended
Provide ongoing general medical support ^r1^r4
- 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 ^r1^r37
- Place intermittent pneumatic compression for prevention of venous thromboembolism beginning the day of hospital admission

Treatment of an unruptured intracranial aneurysm ^r2^r10

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: ^r38^r39
- 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 ^r18
  - 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 ^r40^r41^r42
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 ^r2^r43^r44
- Treat any modifiable risk factors, such as hypertension, and counsel regarding smoking cessation and reduction in heavy alcohol consumption ^r18
  - 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 ^r2^r43
- Many experts also endorse routine treatment of aneurysms between 5 and 7 mm in size ^r43
- The optimal treatment modality for preventive repair has not been definitely established ^r18
  - Endovascular coiling ^r2^r10
    - 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 ^r18
    - Associated with lower morbidity and mortality but a higher risk of recurrence than surgical clipping ^r8
  - Microsurgical clipping ^r2^r10
    - 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 ^r18
  - Use of endoluminal flow diversion and liquid embolic agents are additional techniques in development but are not guideline recommended ^r2

Drug therapy

Calcium channel blockers ^r1
- Nicardipine ^c119
  - 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 ^c120
  - 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 ^r1
- Esmolol ^c121
  - 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 ^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, 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 ^r4
- Lorazepam ^c123
  - 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 ^c124
  - 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

Hydration with isotonic saline ^r1^c125

Infuse isotonic saline to maintain euvolemia to prevent delayed cerebral ischemia ^c126

Glucose management ^c127

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

Control of hyponatremia ^c128

Administer corticosteroids and infusion of 3% hypertonic saline to control hyponatremia

Procedures

Microsurgical clipping ^r10^c129

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 ^r2
- 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 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 ^r2

Complications

Failure of clipping, bleeding or rebleeding of aneurysm, seizures, stroke, infection, impaired cognition, and decreased independence with activities of daily living

Endovascular coiling ^r2^c130

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 ^r2
- Preferred for aneurysm in posterior circulation, size greater than 5 mm, and other aneurysm characteristics that may favor endovascular coiling over clipping ^r2^r10
- 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 ^r2
- Treatment of unruptured intracranial aneurysms in patients with family history of intracerebral aneurysm is indicated ^r2
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 ^r46^c131

General explanation

Placement of drain in lateral ventricle with external drainage

Indication

Elevated intracranial pressure secondary to acute hydrocephalus with decreased level of consciousness ^r4

Contraindications

Coagulopathy, thrombocytopenia

Complications

Bleeding, infection

Comorbidities ^c132

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 identified as incidental finding on vascular imaging
- Vascular imaging surveillance is recommended owing to potential for growth and rupture of untreated and unruptured aneurysms ^r48
- CT angiography and magnetic resonance angiography are the most appropriate modalities; CT angiography is less sensitive at detecting aneurysms smaller than 3 mm in size and those adjacent to osseous structures ^r48^c133^c134^c135
- 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 ^r2^r44
  - Most experts favor lifelong surveillance ^r44
- Follow-up imaging demonstrating aneurysm growth, aneurysm irregularity, or enhancement of the aneurysm wall suggests increased risk for rupture and treatment may be warranted ^r49
Follow-up imaging of previously treated cerebral aneurysms ^r2
- Long-term surveillance imaging is recommended after treatment to monitor for refilling of the treated aneurysm, integrity of the parent vessel, and development of new aneurysms ^r1^r48
  - There are no guideline recommendations for frequency of monitoring after surgical intervention
- Cervicocerebral arteriography is the reference standard imaging examination ^r48^c136^c137
- Magnetic resonance angiography is the most commonly used noninvasive examination ^r48
  - Magnetic resonance angiography or CT angiography may be used; however, the presence of metallic coils and other endovascular devices may limit the utility of these modalities

Complications and Prognosis

Complications

For unruptured aneurysm
- Growth that causes symptomatic impingement on cerebral structures or cranial nerves ^c138
- Rupture ^c139
For ruptured aneurysm
- Rebleeding ^c140
  - 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 ^r1^r50
  - Incomplete initial obliteration of the aneurysm is a risk factor for recurrent hemorrhage ^r1
- Hyponatremia ^r51^c141
  - 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 ^r52
- Angiographic vasospasm and delayed cerebral ischemia ^r53^r54^c142
  - 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 ^c143
  - Occur in approximately 6% to 18% of ruptured aneurysm cases ^r1
  - Delayed seizures occur in 3% to 7% of cases ^r1
- Hydrocephalus ^r11^r55^c144
  - Acute hydrocephalus can occur in approximately 20% to 67% of patients within 3 days after a ruptured aneurysm ^r11^r55
  - 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 ^r56^c145
- Anemia can occur in 18% of cases after aneurysmal subarachnoid hemorrhage ^r57^c146
- Heparin-induced thrombocytopenia occurs in 5% of patients with aneurysmal subarachnoid hemorrhage ^r1^c147
  - 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 ^r58^c148

Prognosis

Unruptured cerebral aneurysms can go unnoticed throughout a person's life
- Prevalence of unruptured intracerebral aneurysms is 2.8% ^r17
- Estimated rate of rupture of intracerebral aneurysm is 0.25% per year for the general population with aneurysm ^r2
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 ^r2

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 ^r2^r3^r8
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 ^r2^r8

Screening tests ^r2

Magnetic resonance angiography ^c149
CT angiography ^c150

Prevention

Preventive measures to decrease risk of aneurysm rupture leading to subarachnoid hemorrhage include the following: ^r1^r2
- Avoidance of tobacco ^r23^c151
- Avoidance of excessive alcohol consumption ^c152
- Treatment of hypertension may provide some decreased risk of aneurysm growth and rupture ^c153

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Cerebral Aneurysm

Synopsis

Key Points

Urgent Action

Pitfalls

Terminology

Clinical Clarification

Classification

Diagnosis

Clinical Presentation

History

Physical examination

Causes and Risk Factors

Causes

Risk factors and/or associations

Age

Sex

Genetics

Ethnicity/race

Other risk factors/associations r2

Diagnostic Procedures

Primary diagnostic tools

Laboratory

Imaging

Procedures

Lumbar puncture c112

General explanation

Indication

Contraindications

Complications

Interpretation of results

Differential Diagnosis

Most common

Treatment

Goals

Disposition

Admission criteria

Criteria for ICU admission

Recommendations for specialist referral r5

Treatment Options

Drug therapy

Nondrug and supportive care

Procedures

Microsurgical clipping r10c129

Endovascular coiling r2c130

Ventricular drain placement r46c131

Comorbidities c132

Special populations

Monitoring

Complications and Prognosis

Complications

Prognosis

Screening and Prevention

Screening

At-risk populations r2

Screening tests r2

Prevention

Other risk factors/associations ^r2

Lumbar puncture ^c112

Recommendations for specialist referral ^r5

Microsurgical clipping ^r10^c129

Endovascular coiling ^r2^c130

Ventricular drain placement ^r46^c131

Comorbidities ^c132

At-risk populations ^r2

Screening tests ^r2