Elias Atallah

Off-label uses of the Pipeline embolization device: a review of the literature

The Pipeline embolization device (PED) is the most widely used flow diverter in endovascular neurosurgery. In 2011, the device received FDA approval for the treatment of large and giant aneurysms in the internal carotid artery extending from the petrous to the superior hypophyseal segments. However, as popularity of the device grew and neurosurgeons gained more experience, its use has extended to several other indications. Some of these off-label uses include previously treated aneurysms, acutely ruptured aneurysms, small aneurysms, distal circulation aneurysms, posterior circulation aneurysms, fusiform aneurysms, dissecting aneurysms, pseudoaneurysms, and even carotid-cavernous fistulas. The authors present a literature review of the safety and efficacy of the PED in these off-label uses.

Flow diversion with the pipeline embolization device for patients with intracranial aneurysms and antiplatelet therapy: A systematic literature review

Flow diversion with the Pipeline Embolization Device (PED) is reported as a safe and efficient treatment for patients with intracranial aneurysms; however, literature discussing the antiplatelet (APT) regimen used before and after the PED is limited. Our aim was to systematically review and summarize available data regarding the APT regimen and the platelet function test (PFT) that was used. We also sought to provide an overview of the aneurysm morphologies and adverse event rates associated with the PED use. This systematic review was conducted according to the PRISMA statement and eligible studies were identified through search of the PubMed and Cochrane databases. We reviewed 28 studies, involving 1556 patients that underwent aneurysm treatment with the PED. The preprocedural aspirin (ASA) 300- 325mg (2-14days) combined with clopidogrel 75mg (3 to >10days) were used as a treatment strategy in 61.7% of patients and ASA 81mg with clopidogrel 75mg for 5-10days for 27%. Patients who received low versus high dose pre-PED ASA, were at less risk for a hemorrhagic event (0.7% versus 3.3%, p=0.053); however no statistical significance was reached. There was also lack of relationship between patients that received low versus high preprocedural ASA in terms of thromboembolic events. Regarding postprocedural APT, ASA (>6months) and clopidogrel (3- 12 months) was the regimen of choice for 93% of patients. Most studies conducted at least one PFT, most common being the VerifyNow. The most frequently reported target P2Y12 Reaction unit (PRU) and Aspirin Reaction Unit (ARU) values were <230 and <550 respectively. There was no statistically demonstrable difference in regards to thrombotic events between centers that conducted at least one PFT and centers that did not test their patients with a PFT. The overall rates of symptomatic thrombotic episodes were 6.6% and hemorrhagic were 3%. The pre- and post-PED APT dose and duration varies across different institutions. More prospective studies are needed to compare the efficacy of different APT agents and reach conclusions regarding use of PFT and platelet reaction values in order to decrease hemorrhagic and thromboembolic complications associated with the PED.

Acute Recanalization of a Partially Thrombosed Large Intracranial Aneurysm

BACKGROUND Thrombosed large intracranial aneurysms (TLIAs) are not continuously contemplated as stable lesions. Spontaneous recanalization of completely occluded large intracranial aneurysms has been described previously. CASE DESCRIPTION We report a middle-aged patient presenting with agitation, acute headache, visual field defects, and left hemiparesis. A large thrombosed posterior communicating (PCom) artery aneurysm was identified with an infarct at the same arterial territory on neuroimaging studies. Digital subtraction angiography (DSA) performed 1 week later demonstrated complete recanalization of the TLIA. It was treated endovascularly with coils. The patient returned several days later with augmenting headaches due to quadrigeminal system subarachnoid hemorrhage. Repeat DSA showed filling of the coiled aneurysm from the internal carotid artery injection. The PCom artery was catheterized and deconstructed. The patient was discharged to home with no additional neurologic deficits. CONCLUSIONS TLIAs are insidious vascular lesions. They can cause nerve or vessel damage by a mass effect or through ischemic stroke by emitting emboli into distal vasculature. We advise close periodic radiologic follow-up for TLIAs.

Aneurysms with persistent filling after failed treatment with the Pipeline embolization device

OBJECTIVEThe Pipeline embolization device (PED) has become a valuable tool in the treatment of cerebral aneurysms. Although failures with PED treatment have been reported, the characteristics and course of these aneurysms remain a topic of uncertainty.METHODSElectronic medical records and imaging studies were reviewed for all patients treated with the PED between July 2010 and March 2015 to identify characteristics of patients and aneurysms with residual filling after PED treatment.RESULTSOf 316 cases treated at a single institution, 281 patients had a long-term follow-up. A total of 52 (16.4%) aneurysms with residual filling were identified and constituted the study population. The mean patient age in this population was 58.8 years. The mean aneurysm size was 10.1 mm ± 7.15 mm. Twelve aneurysms were fusiform (23%). Of the aneurysms with residual filling, there were 20 carotid ophthalmic (CO) aneurysms (20% of all CO aneurysms treated), 10 other paraclinoid aneurysms (16.4% of all paraclinoid aneurysms), 7 posterior communicating artery (PCoA) aneurysms (21.9% of all PCoA aneurysms), 7 cavernous internal carotid artery (ICA) aneurysms (14.9% of all cavernous ICA aneurysms), 4 vertebrobasilar (VB) junction aneurysms (14.8% of all VB junction aneurysms), and 3 middle cerebral artery (MCA) aneurysms (25% of all MCA aneurysms). Eleven patients underwent placement of more than one PED (21.2%), with a mean number of devices of 1.28 per case. Eight of 12 aneurysms were previously treated with a stent (15.4%). Nineteen patients underwent re-treatment (36.5%); the 33 patients who did not undergo re-treatment (63.5%) were monitored by angiography or noninvasive imaging. In multivariate analysis, age older than 65 years (OR 2.65, 95% CI 1.33-5.28; p = 0.05), prior stent placement across the target aneurysm (OR 2.94, 95% CI 1.15-7.51; p = 0.02), aneurysm location in the distal anterior circulation (MCA, PCoA, and anterior choroidal artery: OR 2.72, 95% CI 1.19-6.18; p = 0.017), and longer follow-up duration (OR 1.06, 95% CI 1.03-1.09; p < 0.001) were associated with incomplete aneurysm occlusion.CONCLUSIONSWhile the PED can allow for treatment of large, broad-necked aneurysms with high efficacy, treatment failures do occur (16.4%). Aneurysm size, shape, and previous treatment may influence treatment outcome.

Pipeline-assisted coiling versus pipeline in flow diversion treatment of intracranial aneurysms

BACKGROUND AND PURPOSE Flow-diversion therapy (FDT) for large and complex intracranial aneurysms is effective and considered superior to primary coil embolization. Data evaluating common treatment with both FDT and coiling continues to emerge, but information on outcomes remains scarce. This study aims to examine further the efficiency and outcomes correlated with joint FDT using pipeline embolization device (PED) and coiling compared to PED-alone in treating intracranial aneurysms. MATERIALS AND METHODS Comparative review and analysis of aneurysm treatment with PED in 416 subjects were conducted. Joint modality, PED, and coiling were compared to PED-alone for aneurysm occlusion, recurrence, retreatment, thromboembolic or hemorrhagic events, and functional outcome using the modified Rankin Scale. Data on patient demographics, aneurysm characteristics, clinical and angiographic follow up, were also collected. Both univariate analysis and multivariate logistic regression modeling using mixed-effects were performed. RESULTS Total of 437 aneurysms were treated using PED of which 74 were managed with both PED and coiling. Average patient-age was 56 years, the majority were men (85%), an average aneurysm size was 9 mm, and the majority were saccular aneurysms (84%). Larger aneurysm size was associated with a poor outcome in patients with unruptured aneurysms (OR = 1.06). Adjusted regression analyses revealed no differences between treatment groups in thromboembolic or hemorrhagic events, aneurysm occlusion rate, residual flow on follow up angiography, or functional outcome. CONCLUSIONS Treatment of intracranial aneurysms with joint PED and coiling was safe with no increase in complications when compared to PED alone. Aneurysm occlusion rates and functional outcome with PED and coiling stays comparable to treatment with PED-alone.

Remote Thoracic Myelopathy From a Spinal Dural Arteriovenous Fistula at the Craniocervical Junction: Case Report and Review of Literature

BACKGROUND The craniocervical junction is a rare location for spinal dural arteriovenous fistulas (dAVFs). Typically, fistulas at this location present with findings related to intracranial cortical venous reflux or cervical myelopathy. We present a case of craniocervical junction dAVF with isolated clinical and radiographic findings of thoracolumbar myelopathy. CASE DESCRIPTION A 54-year-old man presented with subacute onset of lower extremity weakness, paresthesias, and gait dysfunction. Routine spine magnetic resonance imaging demonstrated edema of the conus medullaris and distal thoracic spinal cord and prominent dorsal venous flow voids, suggestive of a thoracolumbar dAVF. Spinal angiography performed at an outside institution failed to demonstrate a fistula. Noninvasive spinal angiographic imaging with time-resolved magnetic resonance angiography (TR-MRA) performed at our institution was able to demonstrate presence of the fistula at the craniocervical junction. Subsequent cerebral angiography identified feeding vessels arising from the posterior meningeal artery and ascending pharyngeal artery on the right side. The fistula was successfully embolized with onyx embolic material, with rapid resolution of his clinical symptoms. CONCLUSIONS Isolated lower extremity myelopathic symptoms are a rarely reported finding in patients harboring craniocervical junction dAVFs. At our institution, noninvasive imaging with TR-MRA is routinely used to aid localization of dAVFs. This results in decreased contrast dose and radiation exposure, and inclusion of the cervical spine should be performed when thoracolumbar imaging fails to identify a dAVF prior to proceeding to invasive angiography.

Spinal Glomus Arteriovenous Malformation Manifesting with a Subarachnoid Hemorrhage

BACKGROUND Spinal arteriovenous malformations (AVMs) are rare lesions that may cause serious neurologic morbidity. With developments in endovascular technology and embolic materials, endovascular management of spinal AVMs has gained popularity. CASE DESCRIPTION A 61-year-old woman presented with the worst headache of her life and an acute onset of nausea and vomiting and was shown to have a grade 2 subarachnoid hemorrhage (SAH) on computed tomography scan. A 6-vessel cerebral angiogram was negative for any vascular abnormalities. Magnetic resonance imaging and magnetic resonance angiography of the neck showed a flow-related enhancement compatible with a vascular abnormality at the level of C2. Cervical spinal angiography showed a cervical spinal cord glomus (type II) AVM at the level of C2 draining into perimedullary venous plexus. Transarterial Onyx embolization was performed and resulted in complete occlusion of the AVM. The patient made a complete neurologic recovery. CONCLUSIONS Spinal AVMs manifesting as intracranial SAH are uncommon. These lesions are frequently overlooked on cerebral angiography and account for a small proportion of angiogram-negative SAHs. A negative angiogram in the setting of SAH should prompt a comprehensive evaluation of the cervical segmental arterial supply to exclude a cervical spinal AVM. Endovascular embolization may be effective in treating spinal glomus AVMs with good clinical outcomes and with complete angiographic obliteration. Onyx embolic agent should be considered as the agent of choice to manage spinal glomus AVMs.

Transcirculation Pipeline embolization device deployment: a rescue technique

The Pipeline embolization device (PED) has become a very important tool in the treatment of nonruptured cerebral aneurysms. However, a patients difficult anatomy or vascular stenosis may affect the device delivery. The purpose of this article was to describe an alternate technique for PED deployment when ipsilateral anatomy is not amenable for catheter navigation. A 44-year-old woman with a symptomatic 6-mm right superior hypophyseal artery aneurysm and a known history of right internal carotid artery dissection presented for PED treatment of her aneurysm. An angiogram showed persistence of the arterial dissection with luminal stenosis after 6 months of dual antiplatelet treatment. The contralateral internal carotid artery was catheterized and the PED was deployed via a transcirculation approach, using the anterior communicating artery. Transcirculation deployment of a PED is a viable option when ipsilateral anatomy is difficult or contraindicated for this treatment.

Aspirin for the Prevention of Intracranial Aneurysm Rupture

∗Department of Neurosurgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania; ‡Department of Neurological Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers University, NewBrunswick, New Jersey; §Department of Neurosurgery, Miami Miller School of Medicine, Miami University Hospital, Miami, Florida; ¶Department of Neurosurgery, University of Iowa, Iowa City, Iowa

The use of alternatives to clopidogrel in flow-diversion treatment with the Pipeline embolization device

OBJECTIVEThromboembolic complications continue to be encountered with Pipeline embolization devices (PEDs) despite routine clopidogrel/aspirin antiplatelet therapy. This study examined the safety and efficacy of prasugrel in the management of clopidogrel-resistant patients treated for cerebral aneurysms.METHODSFour hundred thirty-seven consecutive patients were identified between January 2011 and May 2016. Patients allergic, or having less than 30% platelet inhibition, to a daily 75-mg dose of clopidogrel received 10 mg of prasugrel daily (n = 20) or 90 mg of ticagrelor twice daily (n = 2). The mean (± SD) follow-up duration was 15.8 ± 12.4 months. The primary outcome was the modified Rankin Scale (mRS) score registered before discharge and at each follow-up visit. To control confounding, multivariable mixed-effects logistic regression and propensity score conditioning were used.RESULTSTwenty-six (5.9%) of 437 patients presented with a subarachnoid hemorrhage (SAH). The mean patient age was 56.3 years, and 62 were women (14.2%). One of the 7 patients lost to follow-up received prasugrel. One patient was allergic to clopidogrel and prasugrel simultaneously. All patients receiving prasugrel or ticagrelor (n = 22) had an mRS score ≤ 2 on their latest follow-up visit (mean score 0.67 ± 1.15). In a multivariate analysis, clopidogrel did not affect the mRS score on last follow-up (p = 0.14). Multivariable logistic regression showed that clopidogrel was not associated with an increased long-term recurrence rate (OR 0.17, 95% CI 0.01-2.70, p = 0.21), an increased thromboembolic complication rate (OR 0.46, 95% CI 0.12-1.67, p = 0.24), or an increased hemorrhagic event rate (OR 0.39, 95% CI 0.91-1.64, p = 0.20). None of the patients receiving prasugrel or ticagrelor died or suffered a long-term recurrence or a hemorrhagic event; only 1 patient suffered from mild aphasia subsequent to a thromboembolic event. Three patients taking clopidogrel died during the study: 2 from acute SAH and 1 from intraparenchymal hemorrhage. Clopidogrel was not associated with an increased mortality rate (OR 2.18, 95% CI 0.11-43.27, p = 0.61). The same associations were present in propensity score-adjusted models.CONCLUSIONSIn a cohort of patients treated with PEDs, prasugrel (10 mg/day) was a safe alternative to clopidogrel-resistant or clopidogrel-allergic patients, or nonresponders.