Impact of maternal diabetes exposure on soluble adhesion molecules in the offspring.

BACKGROUND AND AIMS: Soluble adhesion molecules are associated with cardiovascular disease and increased in individuals with diabetes. This study assesses the impact of diabetes exposure in utero on the abundance of circulating adhesion molecules in cord serum and soluble adhesion molecules released from human umbilical vein endothelial cells (HUVEC) exposed to high glucose concentrations. METHODS AND RESULTS: Women with and without diabetes were recruited. DM was diagnosed based on the American Diabetes Association criteria. Primary cultures of HUVEC were cultured in 5 mM and 25 mM glucose with 25 mM mannitol osmotic control. The soluble adhesion molecules, intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and E-selectin were measured by ELISA in the cord blood serum and conditioned HUVEC media. The mothers with DM were older with higher BMI (p = 0.027 and 0.008, respectively). In a fully adjusted model, VCAM was significantly increased in the cord serum of infants born to mothers with diabetes (p = 0.046), but ICAM and E-selectin were not different. ICAM was also significantly correlated with maternal HbA1c (r2 = 0.16, p = 0.004) and cord serum non-esterified fatty acids (r2 = 0.08, p = 0.013). From the HUVEC media, the abundance of adhesion molecules was not different based on DM or high glucose exposure; however, VCAM abundance in the HUVEC supernatant was significantly correlated with ICAM (r2 = 0.27, p = 0.010) and cord serum c-peptide (R2 = 0.19, p = 0.043). CONCLUSIONS: Alterations in soluble adhesion molecule abundance in infants exposed to the diabetic milieu of pregnancy may reflect early alterations in vascular function predicting future cardiovascular disease.

A DELPHI consensus statement on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of mechanical thrombectomy.

PURPOSE: There is little data and lack of consensus regarding antiplatelet management for intracranial stenting due to underlying intracranial atherosclerosis in the setting of endovascular treatment (EVT). In this DELPHI study, we aimed to assess whether consensus on antiplatelet management in this situation among experienced experts can be achieved, and what this consensus would be. METHODS: We used a modified DELPHI approach to address unanswered questions in antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. An expert-panel (19 neurointerventionalists from 8 countries) answered structured, anonymized on-line questionnaires with iterative feedback-loops. Panel-consensus was defined as agreement ≥ 70% for binary closed-ended questions/≥ 50% for closed-ended questions with > 2 response options. RESULTS: Panel members answered a total of 5 survey rounds. They acknowledged that there is insufficient data for evidence-based recommendations in many aspects of antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. They believed that antiplatelet management should follow a standardized regimen, irrespective of imaging findings and reperfusion quality. There was no consensus on the timing of antiplatelet-therapy initiation. Aspirin was the preferred antiplatelet agent for the peri-procedural period, and oral Aspirin in combination with a P2Y12 inhibitor was the favored postprocedural regimen. CONCLUSION: Data on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT are limited. Panel-members in this study achieved consensus on postprocedural antiplatelet management but did not agree upon a preprocedural and intraprocedural antiplatelet regimen. Further prospective studies to optimize antiplatelet regimens are needed.

Role of metformin in epigenetic regulation of placental mitochondrial biogenesis in maternal diabetes.

Adverse maternal environments, such as diabetes and obesity, impair placental mitochondrial function, which affects fetal development and offspring long-term health. The underlying mechanisms and effective interventions to abrogate such effect remain unclear. Our previous studies demonstrated impaired mitochondrial biogenesis in male human placenta of diabetic mothers. In the present studies, epigenetic marks possibly related to mitochondrial biogenesis in placentae of women with diabetes (n = 23) and controls (n = 23) were analyzed. Effects of metformin were examined in human placental explants from a subgroup of diabetic women and in a mouse model of maternal high fat diet feeding. We found that maternal diabetes was associated with epigenetic regulation of mitochondrial biogenesis in human placenta in a fetal sex-dependent manner, including decreased histone acetylation (H3K27 acetylation) and increased promoter methylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In male placenta, the levels of H3K27 acetylation and PGC-1α promoter methylation correlated significantly with the activity of AMP-activated protein kinase (AMPK). Metformin treatment on male diabetic placental explant activated AMPK and stimulated PGC-1α expression, concomitant with increased H3K27 acetylation and decreased PGC-1α promoter methylation. In vivo, we show that maternal metformin treatment along with maternal high fat diet significantly increased mouse placental abundance of PGC-1α expression and downstream mitochondrial transcription factor A (TFAM) and inhibited maternal high fat diet-impaired placental efficiency and glucose tolerance in offspring. Together, these findings suggest the capability of metformin to stimulate placental mitochondrial biogenesis and inhibit the aberrant epigenetic alterations occurring in maternal diabetes during pregnancy, conferring protective effects on offspring.

Posterior circulation perforator aneurysms: a proposed management algorithm.

INTRODUCTION: Subarachnoid hemorrhage (SAH) from posterior circulation perforator aneurysms (PCPAs) is rare and its natural history is unknown. Diagnosis may be difficult, acute management is poorly defined, and long-term recurrent SAH rates and clinical outcome data are lacking. METHODS: We searched our institution's records for cases of PCPA rupture and analyzed patient demographics, Hunt and Hess (HH) grades, diagnostic imaging, management, and clinical outcomes. We conducted telephone interviews to calculate modified Rankin Scale (mRS) scores. RESULTS: We identified 9 patients (6 male, 3 female) with a ruptured PCPA who presented to the University of Virginia Health System (Charlottesville, VA, USA) between 2010 and 2016. Median and mean ages were 62 and 63 years, respectively. Median HH grade was 3. Seven of nine (78%) PCPAs were angiographically occult on initial imaging and median time to diagnosis was 5 days. Three conservatively managed patients had a mean mRS score of 0.67 (range 0-1) at mean follow-up of 35.3 months. Antifibrinolytic therapy was administered to all conservatively managed patients without thrombotic complication. Six patients receiving endovascular treatment had a mean mRS score of 2.67 (range 0-6) at mean follow-up of 49.2 months. No cases of recurrent SAH were seen in the study. CONCLUSIONS: The rarity of PCPA has precluded long-term clinical follow-up until now. Our experience suggests low recurrent SAH rates. Until further studies are performed, conservative management, possibly combined with antifibrinolytic therapy, may be a viable treatment with acceptable long-term outcome.

Transorbital Approach for Endovascular Occlusion of Carotid-Cavernous Fistulas: Technical Note and Review of the Literature.

Carotid-cavernous fistulas (CCFs) pose an anatomically and physiologically challenging problem for clinicians. The most common method of treatment for these lesions is transvenous endovascular embolization via the inferior petrosal sinus or the facial vein. When transvenous access is not possible, an alternate approach must be devised. We describe a case example with bilateral Barrow Type B CCFs, which were inaccessible using the traditional transvenous approach. Hence, a direct transorbital approach, performed under fluoroscopic guidance, was employed to successfully obliterate the CCF. At five months follow-up, the patient was recovering without complications. This case delineates the technical aspects of transorbital CCF embolization and demonstrates that this approach is a viable alternative to conventional transvenous methods for appropriately selected CCF cases. We supplement our case example and technical note with a literature review of this approach.

Preoperative Embolization of Cerebral Arteriovenous Malformations with Silk Suture and Particles: Technical Considerations and Outcomes.

OBJECTIVE: Embolization of cerebral arteriovenous malformations (AVMs) is commonly performed prior to surgical resection in order to reduce intraoperative bleeding and improve the safety of resection. Although most modern embolization procedures utilize permanent embolic agents, silk suture and polyvinyl alcohol (PVA) particles may offer unique advantages for preoperative devascularization. The aims of this retrospective cohort study are to describe the technical considerations and determine the outcomes for preoperative silk suture and PVA particle embolization (SPE) of AVMs. MATERIALS AND METHODS: We performed a retrospective review of our AVM embolization database. AVM patients who underwent preoperative SPE and subsequent surgical resection were included for analysis. Baseline patient demographics, AVM characteristics, embolization and operative records, and post-treatment outcomes were reviewed. RESULTS: A total of 11 patients who underwent 12 preoperative SPE procedures were included for analysis. Five AVMs were ruptured (45%), and the median nidus volume was 3.0 cm3 (range: 1.3-42.9 cm3). The Spetzler-Martin grade was I-II in seven patients (64%) and III-IV in four patients (36%). The degree of nidal obliteration was less than 25% in two procedures (17%), 25-50% in one procedure (8%), 50-75% in eight procedures (67%), and greater than 75% in one procedure (8%). The rates of post-embolization AVM hemorrhage and mortality were 8% and 0%, respectively. The postoperative angiographic obliteration rate was 100%, and the modified Rankin Scale score improved or stable in 91% of patients (median follow-up duration 2 months). CONCLUSION: Preoperative AVM SPE affords a reasonable risk to benefit profile for appropriately selected patients.

An overview of antithrombotics in ischemic stroke.

The use of antithrombotic medications is an important component of ischemic stroke treatment and prevention. This article reviews the evidence for best practices for antithrombotic use in stroke with focused discussion on the specific agents used to treat and prevent stroke.

Prevalence of dural venous sinus stenosis and hypoplasia in a generalized population.

BACKGROUND AND PURPOSE: While recent literature has described the prevalence of transverse sinus stenosis in patients with idiopathic intracranial hypertension, tinnitus, and refractory headaches, it is unclear what the prevalence is in the general population. This study evaluates the prevalence of venous sinus stenosis and hypoplasia in the general patient population. MATERIALS AND METHODS: 355 of 600 consecutive patients who underwent CT angiography of the head met the inclusion criteria. The diameters of the dural venous sinuses were recorded. Each study was evaluated by a neuroradiologist for the presence of stenoses. Univariate and multivariate statistical analyses were performed by a statistician. RESULTS: The prevalence of unilateral transverse sinus stenosis or hypoplasia in a sample of patients representing the general population was 33%, the prevalence of bilateral transverse sinus stenosis was 5%, and the prevalence of unilateral stenosis with contralateral hypoplasia was 1%. A multivariate analysis identified arachnoid granulations as a predictor of stenosis (p<0.001). Gender trended toward significance (p=0.094). Race was not a significant predictor of stenosis (p=0.745). CONCLUSIONS: The prevalence of bilateral transverse sinus stenosis in the general population is not trivial. These data may be used as a reference for understanding the mechanistic role of stenoses in idiopathic intracranial hypertension, tinnitus, and refractory headaches.

Comparison of Three Risk Scores to Predict Outcomes of Severe Lower Gastrointestinal Bleeding.

BACKGROUND AND AIMS: Improved medical decisions by using a score at the initial patient triage level may lead to improvements in patient management, outcomes, and resource utilization. There is no validated score for management of lower gastrointestinal bleeding (LGIB) unlike for upper gastrointestinal bleeding. The aim of our study was to compare the accuracies of 3 different prognostic scores [Center for Ulcer Research and Education Hemostasis prognosis score, Charlson index, and American Society of Anesthesiologists (ASA) score] for the prediction of 30-day rebleeding, surgery, and death in severe LGIB. METHODS: Data on consecutive patients hospitalized with severe gastrointestinal bleeding from January 2006 to October 2011 in our 2 tertiary academic referral centers were prospectively collected. Sensitivities, specificities, accuracies, and area under the receiver operator characteristic curve were computed for 3 scores for predictions of rebleeding, surgery, and mortality at 30 days. RESULTS: Two hundred thirty-five consecutive patients with LGIB were included between 2006 and 2011. Twenty-three percent of patients rebled, 6% had surgery, and 7.7% of patients died. The accuracies of each score never reached 70% for predicting rebleeding or surgery in either. The ASA score had a highest accuracy for predicting mortality within 30 days (83.5%), whereas the Center for Ulcer Research and Education Hemostasis prognosis score and the Charlson index both had accuracies <75% for the prediction of death within 30 days. CONCLUSIONS: ASA score could be useful to predict death within 30 days. However, a new score is still warranted to predict all 30 days outcomes (rebleeding, surgery, and death) in LGIB.

Endovascular treatment of ophthalmic artery aneurysms: ophthalmic artery patency following flow diversion versus coil embolization.

BACKGROUND AND PURPOSE: The Pipeline Embolization Device (PED) has been shown to effectively treat complex internal carotid artery aneurysms while maintaining patency of covered side branches. The purpose of this retrospective matched cohort study is to evaluate the effect of flow diversion on the patency of the ophthalmic artery when treating ophthalmic artery aneurysms. METHODS: A retrospective review of our prospectively collected institutional database identified 19 ophthalmic artery aneurysms treated with a PED. These were matched according to aneurysm diameter in a 1:2 fashion to ophthalmic artery aneurysms treated via coil embolization, although it is important to note that there was a statistically significance difference in the neck diameter between the two groups (p=0.045). Clinical and angiographic outcomes were recorded and analyzed. RESULTS: On follow-up angiography, decreased flow through the ophthalmic artery was observed in 26% of the PED cohort and 0% of the coil embolization cohort (p=0.003). No ophthalmologic complications were noted in either cohort. Complete occlusion at 12 months was more common following PED treatment than coil embolization (74% vs 47%; p=0.089), although lower than reported in previous trials. This may be due to inflow into the ophthalmic artery keeping the aneurysm patent. Retreatments were more common following coil embolization than PED (24% vs 11%), but this was not significant (p=0.304). Permanent morbidity rates were not significantly different between the PED (11%) and coil embolization (3%) cohorts (p=0.255). CONCLUSIONS: Our results suggest that ophthalmic artery aneurysms may be adequately and safely treated with either the PED or coil embolization. However, treatment with the PED carries a higher risk of impeding flow to the ophthalmic artery, although this did not result in clinical sequelae in the current study.

Endovascular treatment of unruptured wide-necked intracranial aneurysms: comparison of dual microcatheter technique and stent-assisted coil embolization.

BACKGROUND: Endovascular treatment of wide-necked aneurysms is challenging. Stent-assisted coiling (SAC) is associated with increased complications and requires dual antiplatelet therapy. OBJECTIVE: To compare treatment of unruptured, wide-necked aneurysms with a dual-microcatheter technique (DMT) versus SAC. METHODS: Between 2006 and 2011, 100 patients with unruptured wide-necked intracranial aneurysms were treated with DMT and 160 with SAC. Over time there was a significant decrease in the use of SAC and a corresponding increase in DMT. The investigators matched 60 patients treated with DMT blinded to outcome in a 1:2 fashion based on maximal aneurysm dome diameter with 120 patients treated with SAC. Outcomes were determined with conditional (matched) multivariate analysis. RESULTS: There were no significant differences in patient or aneurysm characteristics between cohorts, including aneurysm diameter, neck width, or volume. Overall packing density and coil volume achieved was not significantly different between cohorts. There were higher rates of overall complications in those receiving SAC (19.2%) compared with DMT (5.0%; p=0.012), but no significant difference in major complications (8.3% vs 1.7%, respectively; p=0.103). At a mean follow-up of 27.0 ± 18.9 months, rates of retreatment did not differ between DMT (15.1%) and SAC (17.7%). Delayed in-stent stenosis occurred in five patients and in-stent thrombosis in four patients treated with SAC. There was no difference in favorable functional outcome (modified Rankin score 0-2) between those treated with DMT (90.6%) compared with SAC (91.2%). CONCLUSIONS: DMT and SAC are effective endovascular approaches for unruptured, wide-necked aneurysms; however, DMT may result in less morbidity. Further long-term studies are necessary to determine the optimal indications for these treatment options.

Stenting of symptomatic intracranial stenosis using balloon mounted coronary stents: a single center experience.

OBJECTIVE: Intracranial atherosclerotic disease is the cause of up to 10% of ischemic strokes and transient ischemic attacks. Intracranial stenting with off-label balloon mounted coronary stents (BMCS) may be a viable alternative for patients with symptomatic intracranial stenosis who fail best medical therapy. DESIGN: Between December 2005 and June 2012, 42 symptomatic intracranial stenoses were treated with a BMCS after failing medical management. Procedural records, clinical outcomes, and imaging follow-up were reviewed. Outcome measurements included technical success rate, morbidity and mortality, long term stent patency, and clinical outcomes, as measured by the modified Rankin Scale. RESULTS: The technical success rate was 98% (41 of 42 lesions). Morbidity within the first 30 days was 7.1% (three of 42 lesions). Overall morbidity, including both periprocedural and long term evaluation, was 9.5% (four of 42 lesions). There were no deaths. Follow-up imaging was available for 30 stents (71%) with an average follow-up time of 35.1 months. Restenosis (>50%) and retreatment were observed in 20% and 10% of cases, respectively. Clinical evaluation by a neurologist ≥ 30 days postprocedure was available in 40 of 42 cases (95%) with an average of 32.1 months. At presentation, 55% of patients had a modified Rankin Scale (mRS) score of ≤ 2. At follow-up, 74% of patients were found to have an mRS score of ≤ 2. CONCLUSIONS: This study suggests that BMCS may benefit patients with symptomatic intracranial stenosis who experience stroke or transient ischemic attack in spite of best medical therapy.

Single-center experience with a dual microcatheter technique for the endovascular treatment of wide-necked aneurysms.

OBJECT: The endovascular treatment of wide-necked aneurysms can be technically challenging due to distal coil migration or impingement of the parent vessel. In this paper, the authors illustrate an alternative method for the treatment of wide-necked intracranial aneurysms using a dual microcatheter technique. METHODS: The authors' first 100 consecutive patients who underwent coil embolization of a wide-necked aneurysm using a dual microcatheter technique are reported. With this technique, 2 microcatheters are used to introduce coils into the aneurysm. The coils are deployed either sequentially or concurrently to form a stable construct and prevent coil herniation or migration. Angiographic and clinical outcomes are reported. RESULTS: The technical success rate of the dual microcatheter technique is 91% with a morbidity and mortality of 1% and 2%, respectively. Clinical outcomes are excellent with 93% of patients demonstrating a modified Rankin Scale score of 0-2 at long-term follow-up regardless of their score at presentation. Retreatment rates are 18%. CONCLUSIONS: The dual microcatheter technique may be a safe and efficacious first line of treatment for widenecked aneurysms.

Balloon anchor technique for pipeline embolization device deployment across the neck of a giant intracranial aneurysm.

Treatment of giant intracranial aneurysms, via either surgical or endovascular approaches, is associated with a high level of technical difficulty as well as a high rate of treatment-related morbidity and mortality. Flow-diverting stents, such as the Pipeline embolization device (PED), have drastically altered the therapeutic strategies for the treatment of giant aneurysms. Gaining endovascular access using a microcatheter to the portion of the parent artery distal to the aneurysm neck is requisite for safe and effective stent deployment. Giant aneurysms are often associated with vascular tortuosity, which necessitates significant catheter support systems to enable maneuvering of PEDs across the aneurysm neck. This is also required in order to reduce the probability of stent herniation within giant aneurysms. We report on a case of a giant supraclinoid internal carotid artery (ICA) aneurysm which was treated successfully with a PED utilizing a balloon anchor technique to facilitate direct microcatheter access across the aneurysm neck.

DynaCT imaging for intraprocedural evaluation of flow-diverting stent apposition during endovascular treatment of intracranial aneurysms.

The treatment of large, complex intracranial aneurysms is being increasingly performed using flow-diverting stents (FDS) such as the Pipeline Embolization Device (PED; ev3, Irvine, CA, USA). Malapposition of a FDS to the parent artery wall decreases the likelihood of aneurysm obliteration and increases the risk of both immediate and delayed complications. DynaCT scanning (Siemens Medical Solutions, Erlangen, Germany) is a novel imaging modality which uses a flat plane detector to generate CT images using the same C-arm employed for digital subtraction angiography. We present a 40-year-old woman with an unruptured, 11 mm cavernous internal carotid artery aneurysm who was treated with endovascular obliteration using a PED. Intraprocedural DynaCT scan performed after PED deployment demonstrated incomplete stent apposition to the parent vessel which could not be detected on digital subtraction angiography alone. Balloon angioplasty was performed to improve apposition of the stent to the vessel wall. There were no procedural or clinical complications. The aneurysm shrank in size at follow-up angiography 6 months after the procedure and will be monitored for progressive occlusion. While gross stent malapposition is readily evident after stent deployment, minor instances of malapposition may be undetectable by standard angiography. Therefore the use of DynaCT imaging may improve intraprocedural stent visualization and potentially avert long-term endovascular aneurysm treatment complications associated with inadequate stent apposition.

Endovascular treatment of recurrent intracranial aneurysms following previous microsurgical clipping with the Pipeline Embolization Device.

The treatment of intracranial aneurysms with microsurgical clipping is associated with a very low rate of recurrence. However, in cases of aneurysm recurrence after previous clipping, microsurgical dissection due to adhesions and fibrosis may be challenging, and it may be difficult to safely occlude the recurrent lesion without the risk of significant morbidity. Flow-diverting stents have drastically changed the landscape of endovascular neurosurgery. We present two patients with large, recurrent supraclinoid internal carotid artery (ICA) aneurysms which were previously clipped 17 and 23 years ago at outside institutions. Both recurrent lesions were treated with the Pipeline Embolization Device (PED; ev3 Endovascular, Irvine, CA, USA) without radiographic or clinical complications. In the first patient, the 15 mm aneurysm significantly decreased in size at 6 month angiographic follow-up. The 21 mm aneurysm in the second patient was completely occluded 7 months following PED treatment. The moderate degree of in-stent stenosis present on initial follow-up imaging resolved on angiography 11 months post-treatment. The management of recurrent aneurysms after clipping is sparsely reported in the literature due to its infrequent occurrence. In carefully selected cases, flow-diverting stents may be used for complex aneurysms of the distal ICA, even for those which have recurred following microsurgical clipping.

Intraprocedural retrieval of migrated coils during endovascular aneurysm treatment with the Trevo Stentriever device.

Coil migration during endovascular treatment of intracranial aneurysms occurs in 2-6% of cases. As endovascular coiling of aneurysms has become increasingly popular and as endovascular technology continues to rapidly evolve, the prevalence of intraprocedural coil migration will invariably rise. Since coil masses are highly thrombogenic, migration out of the aneurysm sac into the parent artery may result in large territory infarcts which subsequently manifest as significant neurological morbidity. Therefore safe and timely retrieval of migrated coils is essential to avoiding poor angiographic and clinical outcomes. A 66-year-old woman with an unruptured 5 × 3mm, wide-necked posterior communicating artery aneurysm was referred for endovascular treatment. During coiling with the dual catheter technique, both initially deployed coils dislodged from the aneurysm sac and migrated distally into the middle cerebral artery. After failed retrieval with an Alligator device (Chestnut Medical Technologies, Menlo Park, CA, USA), we used two Trevo devices (Concentric Medical, Mountain View, CA, USA) in succession to successfully retrieve the migrated coils. The aneurysm was then occluded with stent-assisted coil embolization. There were no post-procedural angiographic or clinical complications. The patient was subsequently discharged home without neurological deficit. This case illustrates the first use of the Trevo device for retrieval of migrated coils during endovascular treatment of an intracranial aneurysm to our knowledge. Due to the lack of guidelines defining the standard management of intraprocedural coil migration, current strategies are based on retrospective review of published reports and expert opinion. We present a unique and effective method for endovascular retrieval of displaced coils using a Trevo Stentriever device.