The Need for Better Treatment Options
An aneurysm is an abnormal
localized bulging or ballooning of the wall of a blood vessel. Wide
neck aneurysms are less likely to rupture, but are harder to treat.
A cerebral aneurysm is an abnormal bulging or ballooning of an intercerebral
artery. The prevalence of cerebral aneurysms is in the range of 1-5%.
According to the National Institute of Neurological Disorders and Stroke
(NINDS) of NIH, the incidence of reported ruptured aneurysms is about 10
per 100,000 persons per year (about 27,000 per year in the U.S.)
Approximately one third to one half of people who suffer a ruptured cerebral
aneurysm die within one month and, among those who survive, approximately
one half suffer significant deterioration of brain function. The
vast majority of cerebral aneurysms form in the junction of arteries known
as the Circle of Willis where arteries come together and from which these
arteries send branches to different areas of the brain.
During the past three decades,
there has been a general trend away from surgical clipping and toward less-invasive
endovascular methods of treating aneurysms. Also, there has been
evolution in the less-invasive endovascular methods -- from balloons in
the aneurysm, to coils in the aneurysm, to stents in the parent vessel
before insertion of coils into the aneurysm (sometimes called "stent-assisted
coiling" or "jailing"), to specialized neurological stents that reconstruct
the parent vessel to address the hemodynamic conditions that contributed
to formation of the aneurysm in the first place.
However, the most common
methods of treating aneurysms are still surgical clipping (placing a clamp
on the aneurysm from outside the vessel) and endovascular coiling (inserting
flexible coils into the aneurysm from inside the vessel). Limitations
of clipping include: risks of invasive surgery; difficulty accessing aneurysms
in some areas; difficulty clipping fusiform or wide-neck aneurysms; and
failure to address parent vessel hemodynamics. Limitations of coiling
include: filling only a limited percentage of the aneurysm volume; coil
compaction and recanalization over time; difficulty coiling fusiform or
wide-neck aneurysms; prolapse of coils into the parent vessel; difficulty
clipping later if needed; and failure to address parent vessel hemodynamics.[3-8]
For these reasons, and as
confirmed by the literature, there remains a significant unmet clinical
need for development of new options to treat cerebral aneurysms:
"…there is still significant
room for improvement with respect to the endovascular treatment of aneurysms.
The fundamental shortcoming of coiling technology is that it aims to achieve
endosaccular occlusion of cerebral aneurysms without addressing the diseased
parent vessel that gave rise to the aneurysm. Although this approach is
very effective for many of the small, narrow-necked cerebral aneurysms
that are commonly encountered in practice, the technology fails with more
complex, difficult lesions. The failures of coil embolization are manifest
in two major ways: (1) incomplete treatment (the inability to achieve complete
angiographic occlusion of most lesions), and (2) aneurysm recanalization
(interval coil compaction with time [usually over months] leading to a
deterioration of the results achieved during the original treatment)."
of International Subarachnoid Aneurysm Trial patients documents higher
recurrence and rehemorrhage rates after endovascular coiling."
occurred in 20.8% (95% CI, 19.8% to 21.9%) and retreatment was performed
in 10.3% (95% CI, 9.5% to 11.0%)."
"Recurrences were found
in 33.6% of treated aneurysms that were followed up and that appeared at
a mean+/-SD time of 12.31+/-11.33 months after treatment. Major recurrences
presented in 20.7% and appeared at a mean of 16.49+/-15.93 months."
"Cumulative adverse outcome
rates for endovascular coiling and surgical clipping were 8.8% (95% CI
7.6%-10.1%) and 17.8% (95% CI 17.2%-18.6%)." 
"Initial acute angiographic
results in 1036 aneurysms demonstrated total occlusion in 731 patients
(70.5%), subtotal occlusion in 252 (24.3%), incomplete occlusion in 20
(1.9%), and failures in 33% (3.3%) aneurysms." 
1. Komotar et al., "Guidelines for
the Surgical Treatment of Unruptured Intracranial Aneurysms," Neurosurgery,
2008, 62(1), 183-93.
2. Cerebral Aneurysm Fact Sheet, National
Institute of Neurological Disorders and Stroke,
3. Fiorella, "Endovascular Treatment of
Cerebral Aneurysms. Current Devices, Emerging Therapies, and Future Technology
for the Management of Cerebral Aneurysms," Endovascular Today, June, 2008,
4. Raja et al., "Microsurgical Clipping
and Endovascular Coiling of Intracranial Aneurysms: A Critical Review of
the Literature," Neurosurgery, 62(6), June, 2008, 1187-202.
5. Ferns, S., "Coiling of Intracranial
Aneurysms: A Systematic Review on Initial Occlusion and Reopening and Retreatment
Rates," Stroke, Aug. 1, 2009, 40, e523-e529.
6. Guilbert et al., "Long-Term Angiographic
Recurrences after Selective Endovascular Treatment of Aneurysms with Detachable
Coils," Stroke, 2003, 34, 1398-1403.
7. Lee et al., "Aggregate Analysis of the
Literature for Unruptured Intracranial Aneurysm Treatment," American Journal
of Neuroradiology, Sep., 2005, 26(8), 1902-8.
8. Gallas et al., "Long-Term Follow-Up
of 1036 Cerebral Aneurysms Treated by Bare Coils: A Multicentric Cohort
Treated between 1998 and 2003," American Journal of Neuroradiology, Nov.
1, 2009, 30,1986-1992.