Coil or clip? Current trends in the treatment of intracranial aneurysms

A 27-year-old female developed a severe headache while reaching to adjust her 3-year-old daughter's car seat. She took some ibuprofen (Motrin) and asked a neighbor to watch her child while she took a nap. Three hours later, the neighbor found the woman unconscious and unresponsive and called paramedics. The woman was rushed to a local hospital. Subarachnoid blood was seen on noncontrast CT. The woman was promptly transported via helicopter to a major university medical center.

CT/CT arteriography (CTA) confirmed the diagnosis of hydrocephalus, subarachnoid blood in the anterior fossa, and showed a 7-mm aneurysm on the anterior communicating artery. An external ventricular drain was placed, and 30 cc of CSF was removed. The woman regained sufficient consciousness to be able to follow commands. Digital subtraction angiography further defined the aneurysm morphology. Surgical clipping was deemed the most suitable treatment modality because the aneurysm had a broad neck appearance (see Figure 1).

On postbleed day 3, the patient's sodium level dropped from 141 mEq/L to 128 mEq/L. Treatment was IV administration of 3% sodium chloride and fluid replacement. Results of a vasospasm check on postbleed day 6 indicated moderate to severe vasospasm in the anterior cerebral artery. The patient was given 5 mg of intra-arterial verapamil with good radiographic results. She was discharged on postbleed day 14 to a skilled nursing facility with significant cognitive impairment.

EPIDEMIOLOGY AND RISK FACTORS

SAH commonly occurs in young and middle-age adults. Peak incidence range is age 40 to 60 years.2,3 Of the 25,000 cases of SAH reported in the United States each year, more than 18,000 (72%) patients either die or are left severely disabled.1,2 Rupture of ICAs account for approximately 80% of all cases of SAH.2 Other causes of SAH are trauma, arteriovenous malformation hemorrhage, and dural fistula hemorrhage; however, a cause for SAH may not be determined in all cases.2

Modifiable risk factors for ICA include hypertension and smoking. Nonmodifiable risk factors include advancing age, female gender, and African-American race.1,4 Some diseases are proven to predispose persons to an increased risk of ICA1,5,6 (see “Diseases associated with increased risk of intracranial aneurysm”). However, these diseases account for less than 1% of ICAs.

Population study findings suggest that genetics play a role in risk of aneurysm formation. First-degree relatives of persons with ICAs are four times more likely to develop an ICA than are nonrelatives.1 The Familial Intracranial Aneurysm Study compares DNA samples in families where two or more first-degree relatives (siblings or parent-offspring pairs) have been identified as having ICA. Investigators hope to identify genetic markers for ICA. The influence of factors such as hypertension, smoking, alcohol consumption, and use of birth control pills is also under investigation. More than 450 families have been enrolled. Preliminary evidence links smoking and hypertension to a 20% incidence of ICA formation in persons who are first-degree relatives of a person with an ICA and are older than 30 years.1

At least 1% of the general adult population has intracranial or berry aneurysms,2 many of which do not rupture and are never detected. A diagnosed ICA has a 1% to 2% risk of rupture within 1 year, a 20% risk of rupture within 10 years, and a 35% risk of rupture within 20 years.7 Apart from rupture, some aneurysms are discovered incidentally during a workup for headache, tinnitus, vertigo, or some other condition that prompts cranial imaging studies. Larger ICAs (greater than 2 cm) may exert a mass effect on a nerve, causing cranial nerve palsy, and thereby may be discovered. However, most ICAs remain silent until they rupture.2

Ehlers-Danlos syndrome (incidence, 1 case per 20,000 persons) is a disease of the connective tissues. Characteristics include joint hypermobility and fragile, hyperextensible skin. Ehlers-Danlos syndrome has 11 identified types. Patients with type IV, which is extremely rare but severe, lack type 3 collagen; this causes vascular fragility and increased risk of aneurysm formation.

Marfan syndrome (incidence, 2-3 cases per 10,000 persons) is characterized by abnormal height and cardiac and ocular complications. Patients with Marfan syndrome have a defect in the gene that produces fibrillin, a component of the microfibrils that give connective tissues elasticity. The defect increases the risk of both saccular and fusiform aneurysms of the proximal internal carotid artery.

Autosomal dominant polycystic kidney disease (incidence, 1-2 cases per 1,000 persons) (ADPKD) is the most frequent life-threatening heritable disease. Characterized by enlarged kidneys that form cysts, extra renal complications include intracranial aneurysm formation. The risk for intracranial aneurysm formation in persons with ADPKD is found to be 4% to 11.7%. Ruptured intracranial aneurysm accounts for up to 7% of deaths in patients with ADPKD.

Data from Greenberg MS;3 Schievnick WI;4 Pfohman M and Criddle LM;5 and Schrier RW, Belz MM, Johnson AM, et al. Repeat imaging for intracranial aneurysms in patients with autosomal dominant polycystic kidney disease with initially negative studies: a prospective ten-year follow-up. J Am Soc Nephrol. 2004;15(4):1023-1028.

ANATOMY AND PATHOPHYSIOLOGY

The brain demands 25% of cardiac output. Blood enters the cranial vault under high pressure through the left and right internal carotid arteries and the left and right vertebral arteries. The vertebral arteries join to form the basilar artery; this is the posterior circulation. Each internal carotid artery divides to become anterior cerebral arteries and middle cerebral arteries; this is the anterior circulation. The anterior and posterior circulations join via the posterior communicating arteries at the circle of Willis, which lies at the base of the brain, within the subarachnoid space. ICAs can occur at any of the cerebral vasculature branch points; however, 90% of ICAs occur at the circle of Willis.3

The brain is encased in a sac called the dura mater (literally translated as tough mother). The brain itself is covered with a delicate layer of cells called the pia. The arachnoid consists of filaments that connect the pia and dura mater; the subarachnoid space refers to the CSF-filled space between the brain and the dura mater. The cranial arteries are also within this space. The relative lack of supporting structure, combined with high pressure and numerous branch points, can lead to the formation of ICAs.

An ICA rupture is usually a catastrophic event; it corresponds to the well-known “thunderclap” or sentinel headache.3 The brain is bathed in blood that is leaking into the CSF. Initial bleeding may be controlled by a protective thrombus that forms in the aneurysm lumen. However, ischemia or an infarction may occur in the vessel watershed area; the resultant condition is a decreased global level of consciousness or focal deficit.3,7 SAH is typically associated with a 40% mortality rate and 40% morbidity rate; only 20% of SAH victims return to lives of meaningful function.2

IMAGING MODALITIES

Many imaging modalities are used to diagnose ICA and SAH; however, noncontrast CT is the first-line test for diagnosing acute SAH because it is extremely sensitive to the presence of subarachnoid blood, which shows up as bright white3 (see Figure 2). In addition to being inexpensive and noninvasive, CT allows for a lifesaving diagnosis of occult SAH in the patient with atypical presentations.

CTA illustrates both arterial and venous cerebral vessels. Magnetic resonance arteriography (MRA) may be comparable to CTA, but MRA is more expensive and focuses solely on arterial circulation. Digital subtraction angiography (DSA) is the gold standard for examining cerebral vessels.3,7 DSA is more expensive and more invasive than CTA or MRA but yields significantly more precise and detailed images. Singleplane DSA can construct a 3-dimensional digital model of the aneurysm. Catheter neurointervention with biplane fluoroscopy provides two-plane visualization.

COMPLICATIONS

Hydrocephalus Blood in the subarachnoid space may clot and form a mechanical obstruction of the normal CSF circulation, especially at the sylvian aquaduct. Blood may also interfere with normal reabsorption of CSF at the arachnoid granulation.3 Combined with the edema of ischemic brain parenchyma, blood in the subarachnoid space may cause significantly elevated intracranial pressure (ICP). Normal ICP ranges from 0 to 15 mm Hg. In the patient with SAH, ICP is significantly elevated, which is associated with global obtundation.2,3

The external ventricular drain is used to drain excess cerebral fluid and control ICP. A burr hole is drilled in the skull, and a catheter is inserted into the frontal horn of the lateral ventricle. Fluid is drained into a collecting chamber; raising or lowering the chamber controls the pressure at which the CSF is drawn off. Unconscious or obtunded SAH patients may become awake, alert and orientated ×3 as the ICP returns to normal levels. The external ventricular drain is also indispensable in the ICU because it allows for continuous monitoring of ICP.3

Cerebral salt-wasting syndrome (CSWS) Hyponatremia afflicts 30% to 40% of patients with SAH and is common in patients with intracranial pathology. The condition is implicated in worsening vasospasm and increased ICP, and is a contributing factor to cerebral edema. Hyponatremia may also interfere with normal nerve cell function.8,9

First described by Peters and colleagues in 1950, CSWS is characterized by both a negative sodium balance and volume depletion.10 Hyponatremia occurs in patients with CSWS because the kidneys actively excrete water and sodium. However, hyponatremia occurs in patients with symptoms of inappropriate diuretic hormone (SIADH) because the kidneys retain water and sodium. In patients with cerebral insult, the clinician must not assume that hyponatremia is caused by CSWS because of opposite treatment goals. Rehydration and sodium replenishment are the mainstays of CSWS treatment, whereas fluid restriction is the key in SIADH treatment (see Table 1).Thus, mistaking CSWS for SIADH can have a dire consequence. In one study, 21 of 26 hyponatremic patients with CSWS were treated for SIADH and went on to have a stroke.11

Cerebral vasospasm Endemic to SAH, cerebral vasospasm is thought to be caused by the exposure of arterial vessels in the subarachnoid space to toxic byproducts of blood breakdown. Cerebral vasospasm generally occurs 4 to 14 days postbleed; it may be associated with focal or global deficit or may be clinically silent.3,12 Clinical presentation roughly correlates to the territory of spasm: vasospasm of the right middle cerebral artery manifests as left leg weakness, whereas spasm of the vessels feeding the frontal portion of the brain results in the diminution of thought and personality.

In patients with SAH, cerebral vasospasm is a major cause of morbidity and mortality and, if left unchecked, may lead to stroke or death. Radiographic evidence of vasospasm is seen in 70% of patients with SAH, whereas 30% of patients show clinical signs of the condition.2,3

Therefore, many institutions routinely perform spasmcheck angiography at the peak of occurrence, usually postbleed days 6 to 81,3,12,13 (see Figure 3). This practice allows vasospasm to be anticipated and treated before permanent damage through ischemic stroke can occur.

Treatment usually consists of selective injection of the vessel with verapamil. Nicardipine (Cardene) and nitroglycerin are also commonly used.3,12 Vessels refractory to these agents may require intracranial angioplasty.

Medical management of vasospasm and CSWS is achieved by maintaining a state of hypertension, hemodilution, and hydration, called triple H therapy. Hypertension is artificially induced to raise the mean arterial pressure in an effort to raise the cerebral perfusion pressure. Hemodilution (a hematocrit of 30%-35%) optimizes blood viscosity for oxygen transport. Hyponatremic patients with CSWS require replacement of both salt and water; therefore, adequate hydration must be maintained. Although the effectiveness of this therapy is somewhat controversial, triple H therapy is widely employed.2,3

SURGICAL CLIPPING VS ENDOVASCULAR COILING

Every attempt needs to be made to identify an ICA and secure it. Approximately 80% of all cases of SAH result from ICA rupture. Thrombus formation within the aneurysm lumen halts the initial hemorrhage; however, the fragile structure is at high risk for rebleed, especially within the first 24 to 48 hours.3 Definitive treatment of ICA has evolved in the past 70 years. Current treatment trends are a blend of the old modalities and new technology.

In 1937, Walter Dandy, MD, was the first to successfully place a surgical clip across the neck of an ICA. Dr Dandy deduced the existence of the aneurysm based on the patient's third nerve palsy.14 Surgical clipping remains a mainstay of treatment for ICA. Although the crudely fashioned silver clip used by Dr Dandy has been replaced with nonferromagnetic (MRI safe) titanium clips that are available in a dizzying variety of shapes and sizes, the surgical clip technique remains essentially the same: place a metal clip across the aneurysm neck to cure the condition.

The Guglielmi detachable platinum coil received FDA approval for embolization of brain aneurysms in 1991. Under fluoroscopic guidance, a catheter is advanced through the femoral artery to either the carotid or vertebral artery and into the lumen of the aneurysm. The coil is a metal filament attached, end to end, to a longer guidewire. The filament is advanced through the catheter. The filament coils into a predictable shape that fills the aneurysm as it escapes the catheter tip. Once the filament completely fills the aneurysm, a microcurrent melts the connection between the guidewire and the coil, and the coil-packed aneurysm is considered cured.

Whether the clip or coil is the better method has been a matter of considerable debate. Interventional neuroradiologists argue that coiling is less invasive, involves a shorter hospital stay, and is equally effective in securing the aneurysm. Neurosurgeons argue that a surgical clip has better long-term durability; furthermore some aneurysms will never be suitable for coiling because of their shape.

The International Subarachnoid Aneurysm Trial (ISAT) was a landmark study that compared neurosurgical clipping with endovascular coiling. A cohort of 2,143 patients with ruptured ICA believed to be treatable with either method was randomized. The study was terminated prematurely because coiling reduced the risk of dependency or death by 6.9%, compared to clipping. However, the percentage of incompletely occluded aneurysms was higher in the coiled group than in the clipped group (34% versus 18%). ISAT investigators thereby concluded that endovascular treatment of ruptured ICA is ongoing management rather than a definitive cure. Nevertheless, endovascular treatment can offer lower morbidity and mortality than surgery.15

CONCLUSION

An estimated 1% of the adult population has one or more ICAs and is at risk for SAH.2 The patient introduced in the case study may never regain any further cognition. However, the occurrence of tragic sequelae such as this can be reduced through anticipatory management of the characteristic complications of SAH such as elevated ICP, hyponatremia, and cerebral vasospasm. Careful monitoring and control of ICP with an external ventricular drain, treating hyponatremia in patients with CSWS, and aggressive treatment of cerebral vasospasm are measures that have been proven effective in reducing mortality and morbidity in patients with ICAs. Although surgical and endovascular techniques to secure aneurysms are promising, ongoing scientific studies hold the promise of increasing our understanding and treatment of ICA and SAH. JAAPA

Robert Brach practices at Brigham and Women's Hospital, Children's Hospital Boston, and Harvard Medical School, all in Boston, Massachusetts. He has indicated no relationships to disclose relating to the content of this article.

REFERENCES

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