Discussion

To our knowledge, the two cases presented here are the first examples of endovascular treatment of cerebral aneurysms associated with LDS. The genetic basis of LDS has recently been elucidated.2 The syndrome results from autosomal dominant missense mutations in TGFβR types I or II. These mutations are associated with increased phosphorylation and activity of Smad2, an intracellular mediator and promoter of TGFβ activity. The abnormal activity of TGFβ is thus enhanced by the overabundance of phosphorylated Smad2, and indeed the increase in immunohistochemically detected phosphorylated Smad2 is seen in a variety of collagen vascular disorders in which TGFβ plays a role.8 ,9 While the many effects of such increased signaling are poorly understood, an interaction between fibrillin and other vascular wall components with TGFβ signaling has been demonstrated in animal models.10 ,11 This provides additional evidence for the vascular consequences of increased TGFβ activity.

Histopathological analysis of aortic aneurysms in patients with LDS has shown decreased production and abnormal fragmentation of elastin, as well as abnormal collagen deposition in the tunica media.12 Compared with patients with Marfans syndrome, the aortas of LDS patients showed diffuse, rather than cystic, medial degeneration. In addition, significantly more abnormal collage deposition was seen in LDS patients. Although the significance of these differences is not known, it is postulated that the diffuse nature of the medial degeneration as well as high collagen concentration is responsible for the more aggressive nature of the arterial aneurysms and dissections observed in LDS.9

To our knowledge, this is the first report of the successful treatment of intracranial aneurysms in LDS via the endovascular approach. The above cases illustrate how intracranial stenting provided safe scaffolding for aneurysm coiling without the need for balloon remodeling or extensive microcatheter manipulation within the aneurysms. Because LDS is a rare entity, and intracranial aneurysms from LDS even rarer, the optimal neurosurgical management of LDS patients has yet to be established. Previous reports6 ,7 have noted a hesitancy to treat these aneurysms from an endovascular approach or to use temporary clipping in the open surgical approach due to the friability of the abnormal vessels and their propensity toward vasospasm and/or catastrophic vascular injury. These complications have been seen in the endovascular13–15 and surgical16 treatment of neurovascular pathology in patients with Ehlers–Danlos syndrome IV which is a similar TGFβ connective tissue disorder. However, treatment strategies for aortic manifestations of LDS have included open surgery, endovascular or hybrid approaches with good results, suggesting that the treatment of intracranial aneurysms in this syndrome may be safer than those in patients with Ehlers–Danlos syndrome IV.5 ,17

These concerns shaped the endovascular strategies used to treat these two patients. The advantages of stent assisted coiling in LDS patients remain theoretical. The authors hypothesize that in the diseased vasculature of LDS patients, balloon assisted coiling is to be avoided due to the risk of accidental intraluminal pressure increase and arterial rupture.18 It is postulated that stent assistance provides beneficial flow diversion effects,19 which may further reduce the rate of aneurysm formation in the diseased segments of these two patients' carotid arteries.

Advantages and disadvantages of primary coiling versus stent assistance were discussed with both patients prior to treatment. Both patients expressed a strong interest in maximizing treatment durability. Although the anatomy of the ICA aneurysms in patient No 1 did not demand stent usage, we chose this option for two reasons. The relatively small size as well as orientation of the aneurysms relative to the parent vessel suggested that repeat access might be needed for primary coiling. In aneurysms presumed highly fragile, we hoped to avoid more than one placement of the microcatheter. Similarly, we hoped to minimize the likelihood of recurrence by exploiting flow diversion and remodeling advantages provided by stents. As the aneurysms were fairly proximal, we judged the additional risk of stent placement to be modest and merited.

For patient No 2, the end hole anatomy of the anterior communicating artery aneurysm was deemed to raise the risk of recurrence. Also, to achieve a durable treatment with primary coiling, we felt tight coil packing of the neck would be necessary, an approach we were reticent to use in the presumed very fragile aneurysm. As with patient No 1, we also hoped to exploit flow diversion advantages by stent assistance. The ICA aneurysms in patient No 2 were quite small and we felt delayed treatment following ICA stent placement was best to avoid stent migration during coiling in the difficult access aneurysms. Also, pleased with the successful treatment of the larger more worrisome anterior communicating artery aneurysm, we simply did not wish to push our luck. The delay of 1 year was chosen based on the patient's schedule, as she was traveling from out of state to our center for treatment. The use of a stent in the ICA was chosen as a way to treat a challenging blister aneurysm and for potential diversion advantages. Our understanding of the LDS disease process did not dictate deviation from a standard antiplatelet regimen.

The diseased state of LDS blood vessels has led some authors to recommend open surgical clipping in all intracranial aneurysms in LDS and employ alternatives to traditional methods of proximal aneurysmal control, such as adenosine induced temporary cardiac arrest,6 ,7 as this avoids temporary clipping and further arterial manipulation. While these reports were successful, many other centers do not have the required experience with such complicated microsurgical and neuroanesthetic techniques to perform this procedure safely. In contrast, the two patients we report above were successfully treated with a careful stent coiling technique, which is more widely available in centers around the world.