Edoardo Boccardi

Endovascular Treatment for Acute Ischemic Stroke

BACKGROUND In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed. METHODS We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months. RESULTS A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate. CONCLUSIONS The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA. (Funded by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.).

Midterm and long-term follow-up of cerebral aneurysms treated with flow diverter devices: a single-center experience

OBJECT The introduction of flow diverter devices is revolutionizing the endovascular approach to cerebral aneurysms. Midterm and long-term results of angiographic, cross-sectional imaging and clinical follow-up are still lacking. The authors report their experience with endovascular treatment of intracranial aneurysms using both the Pipeline embolization device and Silk stents. METHODS From October 2008 to July 2011 a consecutive series of 104 intracranial aneurysms in 101 patients (79 female, 22 male; average age 53 years) were treated. Three of the 104 aneurysms were ruptured and 101 were unruptured. Silk stents were implanted in 47 of the aneurysms and Pipeline stents in the remaining 57. In 14 cases a combination of flow diverter devices and coils were used to treat larger aneurysms (maximum diameter > 15 mm). Patients underwent angiographic follow-up examination at 6 months after treatment, with or without CT or MRI, and at 1 year using CT or MRI, with or without conventional angiography. RESULTS In all cases placement of flow diverter stents was technically successful. The mortality and morbidity rates were both 3%. Adverse events without lasting clinical sequelae occurred in 20% of cases. Angiography performed at 6 months after treatment showed complete aneurysm occlusion in 78 of 91 cases (86% of evaluated aneurysms) and subocclusion in 11 (12%); only in 2 cases were the aneurysms unchanged. Fifty-three aneurysms were evaluated at 1 year after treatment. None of these aneurysms showed recanalization, and 1 aneurysm, which was incompletely occluded at the 6-month follow-up examination, was finally occluded. Aneurysmal sac shrinkage was observed in 61% of assessable aneurysms. CONCLUSIONS Parent artery reconstruction using flow diverter devices is a feasible, safe, and successful technique for the treatment of endovascular treatment of cerebral aneurysms.

WEB-DL Endovascular Treatment of Wide-Neck Bifurcation Aneurysms: Short- and Midterm Results in a European Study

Short- and midterm results of endovascular aneurysm treatment with the new WEB-DL device were assessed in 45 patients from 12 European centers. Of these, 42 aneurysms were unruptured and most were located either in the MCA bifurcation or the posterior circulation. Adequate occlusion was observed in 81% and 90% of aneurysms at 6 and 13 months, respectively. Results suggest that WEB endovascular treatment of wide-neck bifurcation aneurysms offers stable occlusion in a class of aneurysms that are historically unstable. BACKGROUND AND PURPOSE: Flow disruption with the WEB-DL device has been used safely for the treatment of wide-neck bifurcation aneurysms, but the stability of aneurysm occlusion after this treatment is unknown. This retrospective multicenter European study analyzed short- and midterm data in patients treated with WEB-DL. MATERIALS AND METHODS: Twelve European neurointerventional centers participated in the study. Clinical data and pre- and postoperative short- and midterm images were collected. An experienced interventional neuroradiologist independently analyzed the images. Aneurysm occlusion was classified into 4 grades: complete occlusion, opacification of the proximal recess of the device, neck remnant, and aneurysm remnant. RESULTS: Forty-five patients (34 women and 11 men) 35–74 years of age (mean, 56.3 ± 9.6 years) with 45 aneurysms treated with the WEB device were included. Aneurysm locations were the middle cerebral artery in 26 patients, the posterior circulation in 13 patients, the anterior communicating artery in 5 patients, and the internal carotid artery terminus in 1 patient. Forty-two aneurysms were unruptured. Good clinical outcome (mRS < 2) was observed in 93.3% of patients at the last follow-up. Adequate occlusion (complete occlusion, opacification of the proximal recess, or neck remnant) was observed in 30/37 patients (81.1%) in short-term follow-up (median, 6 months) and in 26/29 patients (89.7%) in midterm follow-up (median, 13 months). Worsening of the aneurysm occlusion was observed in 2/28 patients (7.1%) at midterm follow-up. CONCLUSIONS: The results suggest that the WEB endovascular treatment of wide-neck bifurcation aneurysms offers stable occlusion in a class of aneurysms that are historically unstable. Additionally, our data show that opacification of the WEB recess can be delineated from true neck or aneurysm remnants.

Utilisation behaviour consequent to bilateral SMA softening.

The case of patient CU, who presented with severe utilisation behaviour, eventually unaccompanied by psychometric signs of frontal involvement, is reported. He suffered from a bilateral stroke within the territory of the anterior cerebral artery. His arterial system was characterised by a unique variant, whereby the right anterior cerebral artery was missing and three trunks originated from the left anterior cerebral artery, each bifurcating into right and left branches. An occlusion of the middle trunk immediately before its partition gave rise to a symmetrical bilateral parasagittal lesion that damaged the supplementary motor areas (medial part of Brodmanns area 6), sparing the lateral regions including the premotor cortices, the corpus callosum and the gyri cinguli. The hypothesis is put forward that utilisation behaviour should be conceived as a double anarchic hand, and its interpretation should rest on the damaged balance between the premotor cortices, responsive to environmental triggers, and the supplementary motor areas, which modulate actions and inhibit them. The imbalance due to the lesion would result in the patients being left at the mercy of environmental stimuli, unable to inhibit inappropriate actions. This intra-frontal hypothesis accounts for the data presented and those from the literature better than the previously held fronto-parietal equipoise.

Hypercoagulability in acute stroke Prognostic significance

To evaluate the clinical significance of hemostatic abnormalities in acute stroke, we studied coagulation and platelet function in 70 patients with recent cerebral infarction or hemorrhage and in 45 age-matched controls. Higher levels of one-stage factor VIII coagulant activity, fibrinopeptide A (FPA), and beta-thromboglobulin were associated with the occurrence of stroke. All hemostatic test results were remarkably similar in patients with ischemic and hemorrhagic stroke. FPA levels and size of the lesion on CT were the only variables independently predicting mortality in a multivariate regression analysis. Our findings demonstrate that hypercoagulability is an important prognostic factor in stroke and lend support to clinical trials of drugs interfering with the coagulation system in the early phase of cerebral ischemia.

Hemorrhage After an Acute Ischemic Stroke

Background and Purpose—Hemorrhagic transformation is frequently seen on CT scans obtained in the subacute phase of ischemic stroke. Its prognostic value is controversial. Methods—We analyzed 554 patients with acute ischemic stroke enrolled in the Multicenter Acute Stroke Trial–Italy (MAST-I) study in whom a second CT scan was performed on day 5. Presence of 1) intraparenchymal hemorrhages (hematoma or hemorrhagic infarction), 2) extraparenchymal bleeding (intraventricular or subarachnoid) and 3) cerebral edema (shift of midline structure, sulcal effacement or ventricular compression) alone or in association were evaluated. Death or disability at 6 months were considered as “unfavorable outcome.” Results—Patients who developed intraparenchymal hemorrhages, extraparenchymal bleeding, or cerebral edema had unfavorable outcome (83%, 100%, and 80%, respectively), but multivariate analysis demonstrated that only extraparenchymal bleeding (collinearity) and cerebral edema (OR=6.8; 95% CI, 4.5 to 10.4) were signi...

Reliability of Hemorrhagic Transformation Diagnosis in Acute Ischemic Stroke

BACKGROUND AND PURPOSE Diagnosis of hemorrhagic transformation (HT) could influence the prognosis and the management of acute ischemic stroke. The interobserver reliability of CT-scan HT classification is evaluated in the present study. METHODS Fifty 5-day CT scans of patients enrolled in the Multicenter Acute Stroke Trial-Italy (MAST-I) were reviewed independently by two neuroradiologists and one neurologist with CT training. They evaluated the presence and type of intraparenchymal HT (hemorrhagic infarction types I, II, and III and intracerebral hemorrhage) (five-item scale), as well as the presence of intraventricular and/or subarachnoid bleeding according to standardized definitions. RESULTS Agreement for exclusion of HT and intraventricular/ subarachnoid bleeding was good between the neuroradiologists (kappa = 0.70 and kappa = 0.72) and excellent between the neurologist and each neuroradiologist (kappa = 0.87 and kappa = 0.77, kappa = 0.83, and kappa = 0.81, respectively). The overall agreement for the five-item HT scale between the two neuroradiologists was good (kappa n = 0.65) because of discordance over the last three items. Better overall agreement was obtained with a three-item scale: no hemorrhage, petechial type I hemorrhagic infarction, and other HT (type II and type III hemorrhagic infarction and intracerebral hemorrhage) together (kappa w = 0.82 CONCLUSIONS Exclusion of HT is a reliable CT diagnosis when made by neuroradiologists and also by a neurologist with CT training. Five- and three-item scales of HT types showed good to excellent reliability. The validity of the scale for predicting short- and long-term outcome should be evaluated in future studies.

Protein C in acute stroke.

The plasma concentrations of protein C, an anticoagulant protein, and fibrinopeptide A were measured in 37 patients with acute hemispheric stroke and in age-matched controls with nonvascular neurologic diseases. In 11 stroke patients who died within 15 days after the onset (nonsurvivors) protein C antigen concentration on admission was lower than in the control group (p less than 0.005), with a mean value of 63% of the concentrations found in the 26 survivors (p less than 0.001). The difference in protein C concentrations was not associated with different prothrombin time ratios and serum albumin concentration in survivors and nonsurvivors of stroke and was independent of the size of the cerebral lesion. Increased fibrinopeptide A concentration on admission was found in all stroke patients (p less than 0.001), but it was higher in nonsurvivors than in survivors (p less than 0.01), suggesting that lower protein C concentrations in nonsurvivors might be due to increased thrombin-dependent protein C activation. In survivors, protein C concentration was slightly but significantly higher than in controls (p less than 0.05) and was unchanged 2 months after stroke, a time when fibrinopeptide A concentrations had returned to normal. These results show that protein C is involved in the hemostatic derangement caused by stroke and provide a rationale for clinical trials evaluating the therapeutic supplementation with protein C of patients with acute ischemic stroke.

Flow diverter devices in ruptured intracranial aneurysms: a single-center experience

OBJECTIVE In this single-center series, the authors retrospectively evaluated the effectiveness, safety, and midterm follow-up results of ruptured aneurysms treated by implantation of a flow diverter device (FDD). METHODS The records of 17 patients (12 females, 5 males, average World Federation of Neurosurgical Societies score = 2.9) who presented with subarachnoid hemorrhage (SAH) due to the rupture of an intracranial aneurysm treated with an FDD were retrospectively reviewed. Of 17 ruptured aneurysms, 8 were blood blister-like aneurysms and the remaining 9 were dissecting aneurysms. The mean delay between SAH and treatment was 4.2 days. Intraprocedural and periprocedural morbidity and mortality were recorded. Clinical and angiographic follow-up evaluations were conducted between 6 and 12 months after the procedure. RESULTS None of the ruptured aneurysms re-bled after endovascular treatment. The overall mortality rate was 12% (2/17), involving 2 patients who died after a few days because of complications of SAH. The overall morbidity rate was 12%: 1 patient experienced intraparenchymal bleeding during the repositioning of external ventricular drainage, and 1 patient with a posterior inferior cerebellar artery aneurysm developed paraplegia due to a spinal cord infarction after 2 weeks. The angiographic follow-up evaluations showed a complete occlusion of the aneurysm in 12 of 15 surviving patients; of the 3 remaining cases, 1 patient showed a remnant of the aneurysm, 1 patient was retreated due to an enlargement of the aneurysm, and 1 patient was lost at the angiographic follow-up. CONCLUSIONS FDDs can be used in patients with ruptured aneurysms, where conventional neurosurgical or endovascular treatments can be challenging.

Treatment of ruptured complex and large/giant ruptured cerebral aneurysms by acute coiling followed by staged flow diversion

OBJECT Flow-diversion treatment has been shown to be associated with high rates of angiographic obliteration; however, the treatment is relatively contraindicated in the acute phase following subarachnoid hemorrhage (SAH) as these patients require periprocedural dual antiplatelet therapy. Acute coiling followed by flow diversion has emerged as an intriguing and feasible treatment option for ruptured complex and giant aneurysms. In this study the authors report outcomes and complications of patients with ruptured aneurysms undergoing coiling in the acute phase followed by planned delayed flow diversion. METHODS This case series includes patients from 2 institutions. All patients underwent standard endovascular coiling in the acute phase after SAH with the intention and plan to proceed with flow diversion at a later date. Outcomes studied included angiographic occlusion, procedure-related complications, and long-term clinical outcome as measured using the modified Rankin Scale. RESULTS A total of 31 patients underwent coiling in the acute phase with the intention to undergo flow diversion at a later date. The mean aneurysm size was 15.8 ± 7.9 mm. Of the 31 patients undergoing coiling, 4 patients could not undergo further flow-diverter therapy: 3 patients (9.7%) died of complications of subarachnoid hemorrhage and 1 patient had permanent morbidity as a result of perioperative ischemic stroke (3.1%). Twenty-seven patients underwent staged placement of flow diverters after adequate recovery. The median time to treatment was 16 weeks. There was one case of aneurysm rebleeding following coil treatment. There were no cases of permanent morbidity or mortality resulting from flow-diverter treatment. Twenty-four patients underwent imaging follow-up; 18 of these patients had aneurysms that were completely or nearly completely occluded (58.1% on an intent-to-treat basis). At last follow-up (mean 18.3 months), 25 patients had mRS scores ≤ 2 (80.6% on an intent-to-treat basis). CONCLUSIONS Staged treatment of ruptured complex and giant intracranial aneurysms with coiling in the acute phase and flow-diverter treatment following recovery from SAH is both safe and effective. In this series, no cases of rebleeding occurred during the interval between coiling and flow diversion. This strategy should be considered as a valid option in patients presenting with these challenging ruptured aneurysms.