Modern Treatment Strategies for Cerebral Aneurysm: Advantages of Disease Orientation
By Jeffrey Thomas, M.D., FACS
Ruptured cerebral aneurysm is among the most lethal of medical conditions, carrying an immediate mortality of 20-30% and 30-day mortality of up to 50% (1). Among the causes of this high secondary mortality, rebleeding is the deadliest, nearly doubling the immediate mortality, and leading to a treatment paradigm that emphasizes early surgery (2). As a consequence, the standard of care in the United States is surgical intervention to eliminate the aneurysm, and the possibility of rebleeding, within 72 hours (3).
The impact of cerebral aneurysm rupture in the subarachnoid space is often catastrophic and brain reaction is severe. Although early surgery is generally advocated, the condition of the injured brain shortly after subarachnoid hemorrhage (SAH) may preclude early craniotomy (Figure 1). Under these circumstances, any advantage that can be gained by a multidisciplinary approach is significant. Most cerebrovascular centers maintain both microneurosurgical and endovascular capability to treat cerebral aneurysm, and the informed consent process for the patient harboring cerebral aneurysm now routinely includes discussion of both options, but the optimal procedure to treat the aneurysm in question is often not known beforehand. Since the procedures are usually carried out in different operating environments, in different departments of the treating hospital, this situation may lead to the need to transfer the critically ill patient between treatment areas of the same hospital, or to a different hospital entirely.
History of coil embolization
Coil embolization was first described by Dr. Sadek Hilal in 1988, greatly improved by implementation of the Guglielmi Detachable Coil (GDC) by Guido Guglielmi in 1990, and the first GDC embolization of a cerebral aneurysm in a human being was performed in 1991 (4,5). This was a transforming event in cerebrovascular neurosurgery, but followed a long history of endovascular procedures for this disease, and others, pioneered by Luessenhop (intracranial vascular catheterization), Mullan (electrical wire thrombosis of cerebral aneurysm), and Serbinenko (balloon embolization of cerebral aneurysm) (6,7) and also Dolenc (copper wire electrothrombosis of cerebral aneurysm) (8). Since 1991, a virtual explosion of digital and endovascular technology has resulted in a dramatic expansion in available neurointerventional treatment options. Endovascular treatments in the form of coils, intracranial stents and balloons now are used to treat over 50% of cerebral aneurysms, and other cerebrovascular disorders, at the California Pacific Neurological Institute.
Table 1: Hunt and Hess grading sccale for aneurysmal subacrachnoid hemorrhage. Percentage according to Hunt and Hess 1968.
Grade I: Asymptomatic or mild headache. Mortality Outcome=11%
Grade II: Moderate to severe headache, or with oculomotor palsy. Mortality Outcome=26%
Grade III: Confused, drowsy, or mild focal signs. Mortality Outcome=37%
Grade IV: Stupor (localized pain). Mortality Outcome=71%
Grade V: Coma (posturing or no motor response). Mortality Outcome=100%
Clinical grading scales used to evaluate the severity of SAH, such as the Hunt and Hess scale (Table 1) have traditionally served as a guideline to the timing of surgical therapy, as well as to prognosis (9). The differences in prognosis between low grade (Grades I and II) and high grade (Grades IV and V) are well-documented9. The impact of technology on this system of triage is significant, in that high-grade aneurysmal SAH patients may now be treated relatively early in order to eliminate rebleeding risk, while simultaneously exposing the critically ill patient to minimal time under general anesthesia and minimal physiological perturbation; importantly, retraction of the acutely damaged brain is entirely eliminated, an enormous advantage in SAH not attainable by the most skillful microneurosurgery. Thus the neurointerventional era has resulted in sometimes life-saving treatment options for the more severe Grade III, IV and even Grade V patients. 
Table 2: CPMC Stroke Volume Chart showing volume for 2007, 2008 and 2009.
2007
First Column = Hemorrhagic stroke transfers: 45
Second Column = Ischemic stroke transfers: 28
Third Column = Total stroke patients: 373
2008
First Column = Hemorrhagic stroke transfers: 67
Second Column = Ischemic stroke transfers: 58
Third Column = Total stroke patients: 444
2009
First Column = Hemorrhagic stroke transfers: 83
Second Column = Ischemic stroke transfers: 107
Third Column = Total stroke patients: 556
At California Pacific Neuroscience Institute, an average of 550 stroke and cerebrovascular patients are treated annually (Table 2). Some 75 of these are patients harboring cerebral aneurysms, among which 60% are treated by neurointerventional means (Table 2). The staggering complexity and variability of this disease has made the combining of surgical and endovascular treatments an invaluable part of the treatment paradigm. Not only is every patient considered for all available treatment options, but it is not uncommon for both neurointerventional and microneurosurgical treatments to be used in the same patient at different times for different aneurysms, in the same patient during a single treatment for multiple aneurysms, or even for the same aneurysm in a single patient. Among neurointerventional treatments alone, stent and balloon adjuncts are occasionally used for coil embolization; more often, as a direct result of the direct juxtaposition and immediate availability of microneurosurgical options, craniotomy and clipping are used as a simpler alternative to complex stacked, if clever, endovascular constructs.
Technique of coil embolization
Endovascular detachable coil embolization is performed with a microcatheter delivered into the target aneurysm over a hydrophilic microguidewire, by way of the bloodstream. The microsystem is introduced to the arterial system through a guiding catheter that is introduced through a 4-millimeter incision over the femoral artery. Other arterial access is occasionally used, such as the brachial artery; for prohibitively tortuous extracranial anatomy, direct surgical access can be made to the carotid or vertebral artery in the neck. The hybrid neurovascular operating suite combines neurointerventional and microneurosurgical capabilities in the same physical space, and is ideal for such combined procedures, as well as for treatment strategies that are changed to match clinical or anatomical circumstances. Unlike craniotomy and other surgery, systemic anticoagulation is used routinely, and both the guiding catheter and microcatheter are flushed constantly with heparinized, pressurized saline. This is a particularly helpful circumstance for patients presenting with other good medical reasons for anticoagulation, like deep vein thrombosis or myocardial ischemia and infarction.
Once microcatheterization is achieved, platinum or platinum composite microcoils are introduced into the aneurysm serially. This process requires estimation of the length, breadth and loop configuration (different for every coil) of the coils, based on the digital measurements made of the aneurysm. Generally the strategy of "basket filling" is used, in which the initial coil is used to create a frame that outlines the walls of the aneurysm, and secondary coils are used to fill in the interior. Each coil is detached electrolytically after it is deployed and determined to be in satisfactory position. Particular attention is paid to the manifest or potential intrusion of coil loops or strands upon the lumen of the parent vessel of the aneurysm. The progress of the embolization is monitored fluoroscopically (coil packing density), and also angiographically (angiography is performed after each coil is deployed, to determine the degree of residual intraaneurysmal filling as well as the condition of the neighboring vasculature). Although the nuances of embolization technique are beyond the scope of this paper, it is necessary to monitor many elements of the process to keep it as predictable as possible. Because thromboembolic phenomena are the principal complication of coil embolization, heparinization is usually performed concomitantly once microcatheterization (and often the framing coil deployment) have been achieved. Often, systemic heparinization is continued for up to 24 hours after the coiling.
In both microneurosurgical and neurointerventional vascular cases, intraoperative monitoring of cortical potential (somatosensory evoked potential, motor evoked potentials and EEG) is routinely used.
Case example 1: Uncomplicated coil embolization
53 year-old female patient presented with subarachnoid hemorrhage, Hunt & Hess Grade III. Cerebral angiography demonstrated an anterior communicating artery aneurysm that was bilobed (Figure 1a).
The patient demonstrated significant blood accumulation in the interhemispheric fissure as well as drowsiness on exam; despite the apparent anatomical complexity of the aneurysm, it was reasoned that she would benefit from coil embolization and the avoidance of brain retraction in the setting of significant brain injury. It was decided that the patient would benefit even from an incomplete coil
embolization, which would protect her against recurrent SAH and allow neurological recovery, pending a definitive procedure (clipping or coiling) as a well patient in the future.
The coil embolization was carried out uneventfully. Despite the complex architecture of the lesion, embolization was complete (Figure 1b). She had serial angiograms for the subsequent two years and demonstrated no residual aneurysm or need for further treatment.
Case example 2: Complication of coil embolization
A 36 year-old female presented with Grade II SAH from a ruptured left middle cerebral artery aneurysm. She was in good neurological condition but presented with morbid obesity (weight 125 kg.), and was felt to be a non-ideal candidate for craniotomy. Although middle cerebral artery (MCA) aneurysms are often best treated by clipping because of their intimate association with distal branches, the patient’s aneurysm was associated with the anterior temporal artery rather than the MCA bifurcation, and appeared to have a saccular configuration. It was decided to attempt coil embolization, which initially appeared successful; a few minutes after successful embolization, however, thrombus was visualized in the parent vessel MCA and carotid artery, followed quickly by thrombotic occlusion. Neurophysiologic cortical potentials (SSEP) began to show an amplitude change of 50% and an increase in latency. Interval angiography showed no residual filling of the ruptured aneurysm after coiling; therefore it was decided to proceed with intraarterial tPA thrombolysis. Although the tPA had the potential to reopen the occluded aneurysm, it was reasoned that this was less likely for a side wall aneurysm beyond the main flow stream of the MCA. Administration of 9.0 mg of intraarterial tPA delivered at the sites of clot deposition completely resolved the obstruction, without any observable effect on the occluded aneurysm. The patient demonstrated slight expressive dysphasia postoperatively, without weakness. She subsequently made a complete neurological recovery.
Special examples illustrating versatility of treatments and clinical decision-making
Case Example 3: Severe SAH, coil to clip
A 52 year-old female presented with massive SAH, coma and respiratory failure, PaO2 = 50, at a nearby community hospital. Myocardial ischemia was present. Clinical Grade V was established; emergency intervention was therefore limited to intubation and ventriculostomy. By the next day, however, she demonstrated responsiveness with GCS score of 2/4/1, and was hemodynamically stable
with no further evidence of myocardial ischemia; on this basis she was transferred to CPNI for further evaluation and treatment. At cerebral angiography a left posterior communicating artery was diagnosed and coiled. Coiling was limited to the fundus because of a perceived wide neck of the aneurysm. The patient went on to make a good neurological recovery (ambulatory and conversant) after VP shunting. One year later the aneurysm demonstrated significant recanalization of the aneurysm neck and was successfully treated by craniotomy and clipping of the remnant, making an excellent ultimate recovery.
Case example 4: Giant basilar apex aneurysm coiled and stented
The patient presented with progressive left hemiparesis and diplopia secondary to a giant aneurysm of the basilar artery. The aneurysm demonstrated calcification near its base on CT exam, making it appear particularly difficult for a surgical approach, but also demonstrated a wide neck with involvement of the right proximal posterior cerebral artery, making it also unsuitable for simple coil embolization. An important additional anatomical feature was that the
aneurysm was clearly embedded in the central nervous tissue of the brainstem. Because the lesion was unruptured, stent-assisted coil embolization was considered a reasonable option. This was offered to the patient, who also received consultation by a second neurosurgeon specifically regarding a clipping strategy.
The patient underwent the staged procedure of insertion of an intracranial stent that bridged the basilar and right posterior cerebral artery (PCA) beneath the aneurysm, followed several weeks later by coil embolization through the stent that obliterated the aneurysm. Immediately following surgery he experienced increased weakness in the right lower extremity.
This quickly improved over the subsequent 24 hours and he was discharged to rehabilitation, where he underwent vigorous treatment and experienced complete neurological recovery, with neither weakness nor diplopia. Subsequent angiograms demonstrated persistent complete occlusion of the aneurysm and preservation of all normal vasculature, including the stented segment. As is often demonstrated with aneurysms causing neurological injury by mass effect, that are coiled, elimination of the pulsatility of the aneurysm appears to have been responsible for the demonstrated neurological improvement.
Case example 5: Ruptured giant MCA aneurysm

66 year-old man presents with headache and SAH in the right Sylvian fissure. He underwent cerebral angiography to determine the optimal treatment option, under a plan to proceed immediately with either coiling or clipping, as is the standard practice at CPNI. Angiography revealed a
giant MCA aneurysm. Because the configuration of the aneurysm was unsuitable for coiling, the patient underwent clip reconstruction of this complex lesion,
with opening and exenteration of the partially thrombosed contents, with complete elimination of the aneurysm. Although a complex alternative of combined endovascular procedures might have been proposed, open microsurgery was a much simpler option for this highly complex, partially thrombosed lesion. This logical management strategy resulted in definitive and uncomplicated treatment of the lesion with excellent outcome.
Case example 6: Ruptured unsecured aneurysm with concomitant vasospasm
32 year-old female presents with high-grade SAH from a middle cerebral artery aneurysm, with concomitant cerebral vasospasm. In this case the patient’s delayed presentation to medical attention resulted in the establishment of cerebral vasospasm, which is usually delayed at least three days beyond SAH and represents a relative contraindication to craniotomy and clipping. If vasospasm is symptomatic its treatment, including induced hypertension and hypervolemia, is particularly hazardous if the ruptured aneurysm is still unsecured. The patient in question demonstrated relentlessly progressive vasospasm, with ischemic consequences for the brain. Consequently she was treated by limited cerebral balloon angioplasty to reestablish normal cerebral blood flow, followed by clipping of the ruptured right MCA aneurysm, the vasospasm contraindication having been removed by the endovascular procedure. Because the aneurysm arose from the MCA bifurcation, its anatomy had precluded coil embolization. Remarkably, by 90 days the patient had experienced a complete neurological recovery.
Case example 7: Nonlocalizing SAH with multiple aneurysms
A 35 year-old female presented with large-volume SAH, clinical Grade III. She was transferred to CPNI from the emergency department of the referring hospital, within several hours of her ictus. The patient demonstrated lethargy on her initial examination, which gradually improved. There was no interval development of hydrocephalus. CT demonstrated very dense SAH throughout the basal cisterns, with blood in the fourth ventricle that suggested a vertebrobasilar ruptured aneurysm. She underwent cerebral angiography that disclosed two aneurysms: one at the vertebrobasilar junction, the other near the right superior cerebellar artery. They were approximately the same size, and had similar saccular configurations, without telltale blips or excrescences. Given the distribution of SAH, either one of these lesions could have been the ruptured aneurysm. The
microsurgical approaches to the two locations were different, creating a 50% chance of operating on the incorrect (unruptured) aneurysm.
It was decided to proceed with coil embolization of the two aneurysms simultaneously. The aneurysms had anatomical configurations (fundus-to-neck ratio) that were favorable for coiling, and it was accomplished for both aneurysms without difficulty. Neither aneurysm showed residual filling. The patient made an excellent and rapid recovery. Although it cannot ever be determined which aneurysm bled, the elimination of both aneurysms eliminates the need to do so.
Conclusions
Neurointerventional treatments and technology have permanently changed the landscape of cerebrovascular neurosurgery. The capability of the sophisticated cerebrovascular treatment center to draw from both endovascular and microneurosurgical disciplines greatly enhances power to treat these patients with highly complex, highly variable and dangerous cerebrovascular lesions. This capability results naturally in a disease-oriented, as opposed to technique-oriented, cerebrovascular center. In many cases the techniques are complementary; in a surprising number, they can enable each other, resulting in a very positive trend of excellent clinical outcomes that would have been utterly impossible a few short years ago (case example 4). The combining of these microsurgical and neurointerventional environments into a single physical space, as exhibited by California Pacific Neuroscience Institute, is rare and adds an incalculable advantage in the treatment of these disorders for the modern cerebrovascular specialist.
References
- Prunell GF, Mathiesen T, Diemer NH, Svendgaard NA: Experimental Subarachnoid Hemorrhage: Subarachnoid blood volume, mortality rate, neuronal death, cerebral blood flow, and perfusion pressure in three different rat models. Neurosurgery 52:165-176, 2003.
- Laidlaw J, Siu K: Poor-grade aneurysmal subarachnoid hemorrhage: Outcome after treatment with urgent surgery. Neurosurgery 53: 1275-1282, 2003.
- Hilal SK, Khandji AG, Chi TL. Synthetic fibre-coated platinum coils successfully used for endovascular treatment of arteriovenous malformations, aneurysms and direct arteriovenous fistulas of CNS. AJNR Am J Neuroradiol 1988; 9: 1030.
- Guglielmi G, Vinuela F, Dion J et al., Electrothrombosis of saccular aneurysms via endovascular approach. Part 2: preliminary clinical experience. J Neurosurg 1991;75:8-14.
- Mullan S, Raimondi AJ, Dobben G, et al.: Electrically induced thrombosis in intracranial aneurysms. J Neurosurg 22: 539-47, 1965.
- Luessenhop AJ, Velasquez AC. Observations on the tolerance of the intracranial arteries to catheterization. J Neurosurg 1964; 21: 85-91.
- Serbinenko FA. Balloon catheterization and occlusion of major cerebral vessels. J Neurosurg 1974; 41: 125-45.
- Komotar R, Schmidt J, Starke R, Claassen J, Wartenberg K, Lee K, Badjatia N, Connolly ES Jr., Mayer S: Resuscitation and Critical Care of Poor-Grade Subarachnoid Hemorrhage. Neurosurgery 64:397-411, 2009.
- Debrun G, Aletich V, Kehrli P, Misra M, Ausman J, Charbel F. Selection of Cerebral Aneurysms for Treatment Using Guglielmi Detachable Coils: The Preliminary University of Illinois at Chicago Experience. Neurosurgery 1998: 43:6, pp 1281-1295.
