John D. Nerva

Treatment outcomes of unruptured arteriovenous malformations with a subgroup analysis of ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-eligible patients.

BACKGROUND The design and conclusions of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) trial are controversial, and its structure limits analysis of patients who could potentially benefit from treatment. OBJECTIVE To analyze the results of a consecutive series of patients with unruptured brain arteriovenous malformations (BAVMs), including a subgroup analysis of ARUBA-eligible patients. METHODS One hundred five patients with unruptured BAVMs were treated over an 8-year period. From this series, 90 adult patients and a subgroup of 61 patients determined to be ARUBA eligible were retrospectively reviewed. A subgroup analysis for Spetzler-Martin grades I/II, III, and IV/V was performed. The modified Rankin Scale was used to assess functional outcome. RESULTS Persistent deficits, modified Rankin Scale score deterioration, and impaired functional outcome occurred less frequently in ARUBA-eligible grade I/II patients compared with grade III to V patients combined (P = .04, P = .04, P = .03, respectively). Twenty-two of 39 patients (56%) unruptured grade I and II BAVMs were treated with surgery without and with preoperative embolization, and all had a modified Rankin Scale score of 0 to 1 at the last follow-up. All patients treated with surgery without and with preoperative embolization had radiographic cure at the last follow-up. CONCLUSION The results of ARUBA-eligible and unruptured grade I/II patients overall show that excellent outcomes can be obtained in this subgroup of patients, especially with surgical management. Functional outcomes for ARUBA-eligible patients were similar to those of patients who were randomized to medical management in ARUBA. On the basis of these data, in appropriately selected patients, we recommend treatment for low-grade BAVMs.

Pipeline Embolization Device as primary treatment for blister aneurysms and iatrogenic pseudoaneurysms of the internal carotid artery

Background Blood blister type aneurysms (BBAs) and pseudoaneurysms create a unique treatment challenge. Despite many advances in open surgical and endovascular techniques, this subset of patients retains relatively high rates of morbidity and mortality. Recently, BBAs have been treated with flow-diverting stents such as the Pipeline Embolization Device (PED) with overall positive results. Methods Four patients presented with dissecting internal carotid artery (ICA) aneurysms treated with the PED (two BBAs presenting with subarachnoid hemorrhage (SAH), two pseudoaneurysms after injury during endoscopic trans-sphenoidal tumor surgery). Results Three patients had a successful angiographic and neurological outcome. One patient with a BBA re-ruptured during initial PED placement, again in the postoperative period, and later died. Primary PED treatment involved telescoping stents in two patients and coil embolization supplementation in one patient. Conclusions The PED should be used selectively in the setting of acute SAH. Dual antiplatelet therapy can complicate hydrocephalus management, and the lack of immediate aneurysm occlusion creates the risk of short-term re-rupture. PED treatment for iatrogenic ICA pseudoaneurysms can provide a good angiographic and neurological outcome.

Cerebral Aneurysms Treated with Flow-Diverting Stents: Computational Models with Intravascular Blood Flow Measurements

BACKGROUND AND PURPOSE: Computational fluid dynamics modeling is useful in the study of the hemodynamic environment of cerebral aneurysms, but patient-specific measurements of boundary conditions, such as blood flow velocity and pressure, have not been previously applied to the study of flow-diverting stents. We integrated patient-specific intravascular blood flow velocity and pressure measurements into computational models of aneurysms before and after treatment with flow-diverting stents to determine stent effects on aneurysm hemodynamics. MATERIALS AND METHODS: Blood flow velocity and pressure were measured in peri-aneurysmal locations by use of an intravascular dual-sensor pressure and Doppler velocity guidewire before and after flow-diverting stent treatment of 4 unruptured cerebral aneurysms. These measurements defined inflow and outflow boundary conditions for computational models. Intra-aneurysmal flow rates, wall shear stress, and wall shear stress gradient were calculated. RESULTS: Measurements of inflow velocity and outflow pressure were successful in all 4 patients. Computational models incorporating these measurements demonstrated significant reductions in intra-aneurysmal wall shear stress and wall shear stress gradient and a trend in reduced intra-aneurysmal blood flow. CONCLUSIONS: Integration of intravascular dual-sensor guidewire measurements of blood flow velocity and blood pressure provided patient-specific computational models of cerebral aneurysms. Aneurysm treatment with flow-diverting stents reduces blood flow and hemodynamic shear stress in the aneurysm dome.

Accuracy of Computational Cerebral Aneurysm Hemodynamics Using Patient-Specific Endovascular Measurements

Computational hemodynamic simulations of cerebral aneurysms have traditionally relied on stereotypical boundary conditions (such as blood flow velocity and blood pressure) derived from published values as patient-specific measurements are unavailable or difficult to collect. However, controversy persists over the necessity of incorporating such patient-specific conditions into computational analyses. We perform simulations using both endovascularly-derived patient-specific and typical literature-derived inflow and outflow boundary conditions. Detailed three-dimensional anatomical models of the cerebral vasculature are developed from rotational angiography data, and blood flow velocity and pressure are measured in situ by a dual-sensor pressure and velocity endovascular guidewire at multiple peri-aneurysmal locations in 10 unruptured cerebral aneurysms. These measurements are used to define inflow and outflow boundary conditions for computational hemodynamic models of the aneurysms. The additional in situ measurements which are not prescribed in the simulation are then used to assess the accuracy of the simulated flow velocity and pressure drop. Simulated velocities using patient-specific boundary conditions show good agreement with the guidewire measurements at measurement locations inside the domain, with no bias in the agreement and a random scatter of ≈25%. Simulated velocities using the simplified, literature-derived values show a systematic bias and over-predicted velocity by ≈30% with a random scatter of ≈40%. Computational hemodynamics using endovascularly measured patient-specific boundary conditions have the potential to improve treatment predictions as they provide more accurate and precise results of the aneurysmal hemodynamics than those based on commonly accepted reference values for boundary conditions.

Outcomes of Multimodality Therapy in Pediatric Patients With Ruptured and Unruptured Brain Arteriovenous Malformations

BACKGROUND Brain arteriovenous malformations (BAVMs) are a frequent cause of pediatric hemorrhagic stroke, which frequently results in significant morbidity and mortality. OBJECTIVE To analyze the results of multimodality treatment for a consecutive series of pediatric patients with ruptured and unruptured BAVMs at a single institution. METHODS Forty patients <18 years of age were retrospectively reviewed. Results were divided by hemorrhage status, ie, ruptured or unruptured, and the intended curative treatment modality, ie, surgical resection or stereotactic radiosurgery. RESULTS Twenty-seven patients (68%) presented with hemorrhage, and 13 patients (32%) presented without hemorrhage. Among ruptured patients, 19 (70%) underwent surgery and 8 (30%) underwent stereotactic radiosurgery. In surviving patients who presented with hemorrhage, 23 of 26 (88%) had a modified Rankin Scale (mRS) score of 0 to 2 at the last follow-up, and 24 of 26 (92%) obtained radiographic cure. For unruptured BAVMs, all 6 patients with grade I to III BAVM obtained radiographic cure and had an mRS score of 0 to 1 at the last follow-up, whereas 1 of 5 patients (20%) with grade IV and V BAVM had BAVM obliteration and a mean mRS score of 1.8 at the last follow-up. In a total of 93.6 years of follow-up from date of presentation to last clinical follow-up, there was 1 hemorrhage (1.1%/y). Of 30 patients with radiographic obliteration, 2 patients had radiographic recurrence (7% incidence). CONCLUSION The majority of ruptured patients had an mRS score of 0 to 2 at the last follow-up and obtained radiographic cure. Unruptured patients with grade I to III BAVMs had superior outcomes compared with those with grade IV and V AVMs. Treatment of grade I to III BAVMs appears safe, and additional study is needed to determine optimal strategies for the management of unruptured grade IV and V BAVMs.

Computational fluid dynamics of cerebral aneurysm coiling using high-resolution and high-energy synchrotron X-ray microtomography: comparison with the homogeneous porous medium approach

Background Computational modeling of intracranial aneurysms provides insights into the influence of hemodynamics on aneurysm growth, rupture, and treatment outcome. Standard modeling of coiled aneurysms simplifies the complex geometry of the coil mass into a homogeneous porous medium that fills the aneurysmal sac. We compare hemodynamics of coiled aneurysms modeled from high-resolution imaging with those from the same aneurysms modeled following the standard technique, in an effort to characterize sources of error from the simplified model. Materials Physical models of two unruptured aneurysms were created using three-dimensional printing. The models were treated with coil embolization using the same coils as those used in actual patient treatment and then scanned by synchrotron X-ray microtomography to obtain high-resolution imaging of the coil mass. Computational modeling of each aneurysm was performed using patient-specific boundary conditions. The coils were modeled using the simplified porous medium or by incorporating the X-ray imaged coil surface, and the differences in hemodynamic variables were assessed. Results X-ray microtomographic imaging of coils and incorporation into computational models were successful for both aneurysms. Porous medium calculations of coiled aneurysm hemodynamics overestimated intra-aneurysmal flow, underestimated oscillatory shear index and viscous dissipation, and over- or underpredicted wall shear stress (WSS) and WSS gradient compared with X-ray-based coiled computational fluid dynamics models. Conclusions Computational modeling of coiled intracranial aneurysms using the porous medium approach may inaccurately estimate key hemodynamic variables compared with models incorporating high-resolution synchrotron X-ray microtomographic imaging of complex aneurysm coil geometry.

Traumatic Fracture of a Polymethyl Methacrylate Patient-Specific Cranioplasty Implant

OBJECTIVE To present a case of a traumatic fracture of a polymethyl methacrylate (PMMA) patient-specific implant (PSI) for cranioplasty. METHODS A 14-year-old boy with a history of right decompressive hemicraniectomy and reconstructive cranioplasty with a PMMA PSI presented after an unhelmeted bicycle accident with somnolence, confusion, seizures, left hemiparesis, and an obviously deformed cranium. RESULTS Computed tomography scan showed a comminuted, depressed fracture of the implant and cerebral contusions. The implant was seen to be shattered, resulting in displaced, overriding fragments and significant damage to underlying brain. The patient remained neurologically stable. To minimize the number of operations, intervention was delayed while a polyetheretherketone PSI was fabricated. During surgery, it was noted that the fractured pieces of the implant had caused dural lacerations, and some pieces were embedded in brain parenchyma. The fractured PMMA was removed, and the new implant was placed. The patient remained hemiparetic and was later transferred to an inpatient rehabilitation facility. CONCLUSIONS PMMA PSIs are commonly used for large defects and generally have good outcomes with low rates of revision. The case report described involves a shattered PMMA PSI after a traumatic impact, which resulted in hemiparesis. The question arises if this type of complication can be easily avoided with the addition of titanium onlay to restrict displacement in the event of fracture. This onlay represents a minor change of technique that could prevent migration of fracture fragments.

Dolichoectatic aneurysms of the vertebrobasilar system: clinical and radiographic factors that predict poor outcomes

OBJECTIVE Fusiform dolichoectatic vertebrobasilar aneurysms are rare, challenging lesions. The natural history of these lesions and medium- and long-term patient outcomes are poorly understood. The authors sought to evaluate patient prognosis after diagnosis of fusiform dolichoectatic vertebrobasilar aneurysms and to identify clinical and radiographic predictors of neurological deterioration. METHODS The authors reviewed multiple, prospectively maintained, single-provider databases at 3 large-volume cerebrovascular centers to obtain data on patients with unruptured, fusiform, basilar artery dolichoectatic aneurysms diagnosed between January 1, 2000, and January 1, 2015. RESULTS A total of 50 patients (33 men, 17 women) were identified; mean clinical follow-up was 50.1 months and mean radiographic follow-up was 32.4 months. At last follow-up, 42% (n = 21) of aneurysms had progressed and 44% (n = 22) of patients had deterioration of their modified Rankin Scale scores. When patients were dichotomized into 2 groups- those who worsened and those who did not-univariate analysis showed 5 variables to be statistically significantly different: sex (p = 0.007), radiographic brainstem compression (p = 0.03), clinical posterior fossa compression (p < 0.001), aneurysmal growth on subsequent imaging (p = 0.001), and surgical therapy (p = 0.006). A binary logistic regression was then created to evaluate these variables. The only variable found to be a statistically significant predictor of clinical worsening was clinical symptoms of posterior fossa compression at presentation (p = 0.01). CONCLUSIONS Fusiform dolichoectatic vertebrobasilar aneurysms carry a poor prognosis, with approximately one-half of the patients deteriorating or experiencing progression of their aneurysm within 5 years. Despite being high risk, intervention-when carefully timed (before neurological decline)-may be beneficial in select patients.

Timing of cranioplasty: a 10.75-year single-center analysis of 754 patients

OBJECTIVE Despite their technical simplicity, cranioplasty procedures carry high reported morbidity rates. The authors here present the largest study to date on complications after cranioplasty, focusing specifically on the relationship between complications and timing of the operation. METHODS The authors retrospectively reviewed all cranioplasty cases performed at Harborview Medical Center over the past 10.75 years. In addition to relevant clinical and demographic characteristics, patient morbidity and mortality data were abstracted from the electronic medical record. Cox proportional-hazards models were used to analyze variables potentially associated with the risk of infection, hydrocephalus, seizure, hematoma, and bone flap resorption. RESULTS Over the course of 10.75 years, 754 cranioplasties were performed at a single institution. Sixty percent of the patients who underwent these cranioplasties were male, and the median follow-up overall was 233 days. The 30-day mortality rate was 0.26% (2 cases, both due to postoperative epidural hematoma). Overall, 24.6% percent of the patients experienced at least 1 complication including infection necessitating explantation of the flap (6.6%), postoperative hydrocephalus requiring a shunt (9.0%), resorption of the flap requiring synthetic cranioplasty (6.3%), seizure (4.1%), postoperative hematoma requiring evacuation (2.3%), and other (1.6%). The rate of infection was significantly higher if the cranioplasty had been performed < 14 days after the initial craniectomy (p = 0.007, Holm-Bonferroni-adjusted p = 0.028). Hydrocephalus was significantly correlated with time to cranioplasty (OR 0.92 per 10-day increase, p < 0.001) and was most common in patients whose cranioplasty had been performed < 90 days after initial craniectomy. New-onset seizure, however, only occurred in patients who had undergone their cranioplasty > 90 days after initial craniectomy. Bone flap resorption was the least likely complication for patients whose cranioplasty had been performed between 15 and 30 days after initial craniectomy. Resorption was also correlated with patient age, with a hazard ratio of 0.67 per increase of 10 years of age (p = 0.001). CONCLUSIONS Cranioplasty performed between 15 and 30 days after initial craniectomy may minimize infection, seizure, and bone flap resorption, whereas waiting > 90 days may minimize hydrocephalus but may increase the risk of seizure.

Radiographic and clinical outcomes in cavernous carotid fistula with special focus on alternative transvenous access techniques

Carotid cavernous fistulae (CCF) are dangerous entities that may cause progressive cranial neuropathy, headache and blindness. Endovascular therapy for CCF is the treatment of choice and can be accomplished with minimal morbidity, but optimal treatment strategies vary according to CCF anatomy. We aimed to define a tailored endovascular treatment algorithm for CCF with a focus on traditional and aberrant venous anatomy. Retrospective cohort analysis of data for 57 patients (age range, 18-90 years, mean 53 years) with CCF (35 direct, 22 indirect) was performed. Treatment was transarterial (n=31), transvenous (n=18), combined (n=2), or observation (n=6). Non-conventional transvenous access (that is, via the facial vein, pterygoid plexus, or via direct puncture of the inferior ophthalmic or frontal vein) was employed in five patients. Mean follow-up period was 12 months. Radiographic cure rate in treated CCF was 96%. Forty-five patients presented with ophthalmic symptoms (chemosis, proptosis, eye pain); all resolved within 6 weeks of successful treatment. Forty-three patients presented with cranial nerve III, IV and/or VI palsy; complete recovery was seen in 54% and partial recovery in 18%. Five patients presented with blindness and five with declining visual acuity. No patient with blindness regained sight after treatment, but all five patients with declining vision recovered some visual acuity. The complication rate was 10.6% (one transient abducens nerve palsy, two symptomatic cerebral infarctions, and three groin hematomas). The permanent complication rate was 3.5%. Multimodal treatment of CCF, including non-traditional routes of transvenous access, results in excellent outcomes and low morbidity.