Multicenter study of the safety and effectiveness of intracranial aneurysm treatment with the p64MW-HPC flow modulation device.

BACKGROUND AND PURPOSE: The new p64 flow diverter with hydrophilic polymer coating (HPC) was designed to reduce thrombogenicity. To date, it is unclear how antithrombogenic surface modifications affect neoendothelialization and thrombus formation in patients with unruptured intracranial aneurysms. The purpose of this study was to evaluate the safety and effectiveness of the p64MW-HPC in the treatment of unruptured aneurysms of small to giant size and of both the anterior and posterior circulation. MATERIALS AND METHODS: Between March 2020 and October 2022 all patients with unruptured intracranial aneurysms treated with the p64MW-HPC were included at five neurovascular centers. Demographic data, aneurysm characteristics, antiplatelet therapy, procedural complications, and clinical and angiographic outcomes were recorded. RESULTS: A total of 100 patients with 100 unruptured intracranial aneurysms met the inclusion criteria. Eighty-three aneurysms were classified as saccular, 12 aneurysms were fusiform, 4 aneurysms dissecting, and 1 aneurysm was blister-like. Dual antiplatelet therapy with Clopidogrel and Aspirin was given in 68 cases, and with Ticagrelor and Aspirin in 24 cases. Technical issues with deployment were encountered in 14 cases (torsion (n = 3), foreshortening (n = 8), and incomplete opening (n = 3)). Ischemic stroke occurred in a total of seven cases. In one patient a wire perforation and subsequent severe ICH occurred. Complete aneurysm occlusion at angiographic follow-up (mean time = 7 months) was seen in 73% and adequate occlusion in 93%. CONCLUSION: This study is the largest multicenter study to date documenting the safety and effectiveness of the new antithrombogenic p64MW-HPC in the treatment of unruptured intracranial aneurysms of the anterior and posterior circulation.

Periprocedural Safety and Feasibility of the New LVIS EVO Device for Stent-Assisted Coiling of Intracranial Aneurysms: An Observational Multicenter Study.

BACKGROUND AND PURPOSE: Stent-assisted treatment techniques can be an effective treatment option for intracranial aneurysms. The aim of this study was to evaluate the periprocedural feasibility and safety of the new LVIS EVO stent for the treatment of intracranial aneurysms. MATERIALS AND METHODS: Patients with intracranial aneurysms treated with the LVIS EVO in 11 European neurovascular centers were retrospectively reviewed. Patient and aneurysm characteristics, procedural parameters, immediate grade of occlusion, and technical and clinical complications were assessed. RESULTS: Fifty-seven patients with 59 aneurysms were treated with the LVIS EVO device; 57.6% of the aneurysms were incidental; 15.3% were acutely ruptured; 15.3% were recanalized or residual aneurysms; and 11.9% were treated for symptoms other than acute hemorrhage. The most frequent aneurysm locations were the middle cerebral artery (25.4%) and the anterior communicating artery (22.0%). The rate of immediate successful deployment was 93.2%. In 6.8% (n = 4) of cases, additional in-stent angioplasty was needed. The immediate complete occlusion rate was 54.2%, while there was a residual aneurysm in 35.6% and a residual neck in 10.2%. Periprocedural technical complications occurred in 7/59 treatments (11.9%; the most frequent technical complication [n = 3] was thrombus formation), which all resolved completely without clinical sequelae. Postprocedural neurologic complications occurred after 4/59 treatments (6.8%; 2 transient ischemic attacks, 1 minor stroke, 1 major stroke), of which only 1 persistent complication was directly related to the procedure (minor stroke in the vascular territory distal to the stent). CONCLUSIONS: The LVIS EVO stent is a safe, feasible device for the treatment of intracranial aneurysms.

The FRED for Cerebral Aneurysms of the Posterior Circulation: A Subgroup Analysis of the EuFRED Registry.

BACKGROUND AND PURPOSE: Flow diversion for the posterior circulation remains a promising treatment option for selected posterior circulation aneurysms. The Flow-Redirection Intraluminal Device (FRED) system has not been previously assessed in a large cohort of patients with posterior circulation aneurysms. The purpose of the present study was to assess safety and efficacy of FRED in this location. MATERIALS AND METHODS: Consecutive patients with posterior circulation aneurysms treated at 8 centers participating in the European FRED study (EuFRED) between April 2012 and January 2019 were retrospectively reviewed. Complication and radiographic and functional outcomes were evaluated. RESULTS: Eighty-four patients (median age, 54 years) with 84 posterior circulation aneurysms were treated with the FRED. A total of 25 aneurysms (29.8%) had previously ruptured, even though most aneurysms were diagnosed incidentally (45.2%). The intradural vertebral artery was the most common location (50%), and saccular, the most common morphology (40.5%). The median size was 7 mm. There were 8 (9.5%) symptomatic thromboembolic and no hemorrhagic complications. Thromboembolic complications occurred mostly (90.9%) in nonsaccular aneurysms. On last follow-up at a median of 24 months, 78.2% of aneurysms were completely occluded. Functional outcome at a median of 27 months was favorable in 94% of patients. All mortalities occurred in patients with acute subarachnoid hemorrhage and its sequelae. CONCLUSIONS: The largest cohort of posterior circulation aneurysms treated with the FRED to date demonstrated favorable safety and efficacy profiles of the device for this indication. Treatment in the setting of acute subarachnoid hemorrhage was strongly related to mortality, regardless of whether procedural complications occurred.

Impact of intravenous thrombolysis and emergent carotid stenting on reperfusion and clinical outcomes in patients with acute stroke with tandem lesion treated with thrombectomy: a collaborative pooled analysis.

BACKGROUND AND PURPOSE: Tandem anterior circulation lesions in the setting of acute ischemic stroke (AIS) are a complex endovascular situation that has not been specifically addressed in trials. We determined the predictors of successful reperfusion and good clinical outcome at 90 days after mechanical thrombectomy (MT) in patients with AIS with tandem lesions in a pooled collaborative study. METHODS: This was a retrospective analysis of consecutive patients presenting to 18 comprehensive stroke centers with AIS due to tandem lesion of the anterior circulation who underwent MT. RESULTS: A total of 395 patients were included. Successful reperfusion (modified thrombolysis in cerebral infarction score 2b-3) was achieved in 76.7%. At 90 days, 52.2% achieved a good outcome (modified Rankin Scale score 0-2), 13.8% suffered a parenchymal hematoma and 13.2% were dead. Lower National Institutes of Health Stroke Scale score [odds ratio (OR), 1.26; 95% confidence intervals (CI), 1.07-1.48, P = 0.004], Alberta Stroke Program Early CT Score ≥7 (OR, 2.00; 95% CI, 1.07-3.43, P = 0.011), intravenous thrombolysis (OR, 1.47; 95% CI, 1.01-2.12, P = 0.042) and stenting of the extracranial carotid lesion (OR, 1.63; 95% CI, 1.04-2;53, P = 0.030) were independently associated with successful reperfusion. Lower age (OR, 1.58; 95% CI, 1.26-1.97, P < 0.001), absence of hypercholesterolemia (OR, 1.77; 95% CI, 1.10-2.84, P = 0.018), lower National Institutes of Health Stroke Scale scores (OR, 2.04; 95% CI, 1.53-2.72, P < 0.001), Alberta Stroke Program Early CT Score ≥7 (OR, 2.75; 95% CI, 1.24-6.10, P = 0.013) and proximal middle cerebral artery occlusion (OR, 1.59; 95% CI, 1.03-2.44, P = 0.035) independently predicted a good 90-day outcome. CONCLUSIONS: Intravenous thrombolysis and emergent stenting of the extracranial carotid lesion were predictors of a successful reperfusion after MT of patients with AIS with tandem lesion of the anterior circulation.

European Multicenter Study for the Evaluation of a Dual-Layer Flow-Diverting Stent for Treatment of Wide-Neck Intracranial Aneurysms: The European Flow-Redirection Intraluminal Device Study.

BACKGROUND AND PURPOSE: Endoluminal reconstruction with flow-diverting stents represents a widely accepted technique for the treatment of complex intracranial aneurysms. This European registry study analyzed the initial experience of 15 neurovascular centers with the Flow-Redirection Intraluminal Device (FRED) system. MATERIALS AND METHODS: Consecutive patients with intracranial aneurysms treated with the FRED between February 2012 and March 2015 were retrospectively reviewed. Complications and adverse events, transient and permanent morbidity, mortality, and occlusion rates were evaluated. RESULTS: During the defined study period, 579 aneurysms in 531 patients (median age, 54 years; range, 13-86 years) were treated with the FRED. Seven percent of patients were treated in the acute phase (≤3 days) of aneurysm rupture. The median aneurysm size was 7.6 mm (range, 1-36.6 mm), and the median neck size 4.5 mm (range, 1-30 mm). Angiographic follow-up of >3 months was available for 516 (89.1%) aneurysms. There was progressive occlusion witnessed with time, with complete occlusion in 18 (20%) aneurysms followed for up to 90 ± 14 days, 141 (82.5%) for 180 ± 20 days, 116 (91.3%) for 1 year ± 24 days, and 122 (95.3%) aneurysms followed for >1 year. Transient and permanent morbidity occurred in 3.2% and 0.8% of procedures, respectively. The overall mortality rate was 1.5%. CONCLUSIONS: This retrospective study in real-world patients demonstrated the safety and efficacy of the FRED for the treatment of intracranial aneurysms. In most cases, treatment with a single FRED resulted in complete angiographic occlusion at 1 year.

Mechanical Thrombectomy with the Embolus Retriever with Interlinked Cages in Acute Ischemic Stroke: ERIC, the New Boy in the Class.

BACKGROUND AND PURPOSE: The Embolus Retriever with Interlinked Cages (ERIC) device is a novel stent retriever for mechanical thrombectomy. It consists of interlinked cages and could improve procedural benchmarks and clinical outcome compared with classic stent retrievers. This study compares the rates of recanalization, favorable clinical outcome, procedural adverse events, and benchmarks between the ERIC device and classic stent retrievers. MATERIALS AND METHODS: From 545 patients treated with thrombectomy between 2012 and 2015, 316 patients were included. The mean age was 69 ±13 years, the mean baseline NIHSS score was 17 ± 5, and 174 (55%) were men. The ERIC was used as the primary thrombectomy device in 59 (19%) patients. In a propensity score matched analysis including the NIHSS score, clot location, delay to groin puncture, neurointerventionalist, and anesthetic management, 57 matched pairs were identified. RESULTS: Patients treated with the ERIC device compared with classic stent retrievers showed equal rates of recanalization (86% versus 81%, P = .61), equal favorable 3-month clinical outcome (mRS 0-2: 46% versus 40%, P = .71), and procedural adverse events (28% versus 30%, P = 1.00). However, in patients treated with the ERIC device, thrombectomy procedures were less time-consuming (67 versus 98 minutes, P = .009) and a rescue device was needed less often (18% versus 39%, P = .02) compared with classic stent retrievers. CONCLUSIONS: Mechanical thrombectomy with the ERIC device is effective and safe. Rates of favorable procedural and clinical outcomes are at least as good as those with classic stent retrievers. Of note, the ERIC device might be time-saving and decrease the need for rescue devices. These promising results call for replication in larger prospective clinical trials.

Safety and Efficacy of Aneurysm Treatment with the WEB: Results of the WEBCAST 2 Study.

BACKGROUND AND PURPOSE: Flow disruption with the Woven EndoBridge (WEB) device is an innovative technique for the endovascular treatment of wide-neck bifurcation aneurysms. The initial version of the device (WEB Double-Layer) was evaluated in the WEB Clinical Assessment of IntraSaccular Aneurysm Therapy (WEBCAST) study, whereas the French Observatory study evaluated both WEB Double-Layer and Single-Layer versions of the device. WEBCAST 2 was designed to evaluate the WEB Single-Layer with Enhanced Visualization. MATERIALS AND METHODS: Patients with wide-neck bifurcation aneurysms for which WEB treatment was possible were included. Clinical data including adverse events and clinical status at 1 month and 1 year were collected and analyzed. A core laboratory evaluated anatomic results at 1 year following the procedure. RESULTS: Ten European neurointerventional centers included 55 patients (38 women; 27-77 years of age; mean, 54.4 ± 10.0 years) with 55 aneurysms. Aneurysm locations were the middle cerebral artery in 25 aneurysms (45.5%), the anterior communicating artery in 16 (29.1%), the basilar artery in 9 (16.4%), and the internal carotid artery terminus in 5 (9.1%). Procedural morbidity and mortality at 1 month were, respectively, 1.8% (1/55 patients) and 0.0% (0/55 patients). Morbidity and mortality at 1 year were, respectively, 3.9% (2/51 patients) and 2.0% (1/51 patients). At 1 year, complete occlusion was observed in 27/50 aneurysms (54.0%); neck remnant, in 13/50 (26.0%); and aneurysm remnant, in 10/50 (20.0%) (adequate occlusion in 40/50, 80.0%). CONCLUSIONS: WEBCAST 2 confirms the high safety and efficacy of WEB aneurysm treatment demonstrated in the WEBCAST and French Observatory studies.

First-In-Man Procedural Experience with the Novel EmboTrap® Revascularization Device for the Treatment of Ischemic Stroke-A European Multicenter Series.

PURPOSE: We describe safety and efficacy aspects of mechanical thrombectomy with the novel stent-type clot retrieval device EmboTrap for revascularization of large-artery occlusions in acute ischemic stroke. MATERIALS AND METHODS: A total of 40 patients with acute ischemic stroke due to large-artery occlusion were treated in five European centers. Clinical and procedural data were collected; self-reported angiographic results and neurologic outcome (discharge and 90 days) were assessed in a standardized manner. RESULTS: The median National Institutes of Health Stroke Scale at admittance was 16; no patient was treated after 12 h. Intravenous thrombolysis (IVT) was received by 65 % of patients. The territorial distribution was as follows: 87.5 % in the anterior circulation: 62.5 % middle cerebral artery and 25 % internal carotid artery (ICA) terminus, comprising 20 % tandem occlusions; and 12.5 % in the posterior circulation, all of which were vertebrobasilar. Revascularization of TICI 2b-3 was achieved in 38 of 40 (95 %) treatments. Additional devices were utilized in 11 of 40 (28 %) cases after a mean of 2.6 passes with EmboTrap prior to switching. The mean number of EmboTrap passes needed was 1.8, with a mean procedural time to reperfusion of 54 min. One patient (2.5 %), who had not received IVT, experienced symptomatic intracranial hemorrhage post-interventionally. Procedural complications were encountered in 2 of 40 cases (5 %); both patients exhibited ICA dissection that was treated conservatively without clinical sequelae. There were no device-related complications. Of 23 available patients, 8 (35 %) had a good outcome after 90 days. CONCLUSION: The procedural results from these five centers suggest that EmboTrap is technically safe. Successful recanalization rates can be expected to be within the range of other stent retrievers.

Preoperative Embolization to Improve the Surgical Management and Outcome of Juvenile Nasopharyngeal Angiofibroma (JNA) in a Single Center: 10-Year Experience.

PURPOSE: Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign neoplasm that occurs almost exclusively in the nasopharynx of adolescent male individuals. METHODS: We performed a retrospective study to determine the efficacy and safety of preoperative embolization and the surgical outcome in patients with JNA in a single-center institution. Fifteen cases undergoing embolization and surgical treatment between April 2003 and February 2013 were evaluated retrospectively. The demographic data, clinical presentation, and treatment were reviewed including the kind of preoperative embolization and different surgical approaches performed. The parameters investigated were the amount of blood loss, the tumor stage, and the rates of recurrence. Subsequently, a comparison was made between patients who had undergone Onyx® embolization versus those who had been embolized with the standard approach. RESULTS: In these 15 patients (mean age, 15 years), a total of 27 surgical procedures were performed. One patient was at stage Ia, two were at stage Ib, two were at stage IIa, six were at stage IIb, one was at stage IIc, and three were at stage IIIa based on the Radkowsky classification. All patients underwent preoperative embolization and subsequent surgery. The surgical approach and the embolization technique varied and evolved during time. The embolization procedure decreased the intraoperative blood loss to a minimum of 250 ml, and with the advent of intratumoral embolization, the rate of recurrence diminished. CONCLUSION: Preoperative Onyx® embolization facilitates the shift in the treatment to endoscopic excision in selected patients, which reduces recurrence rates and overall morbidity.

Enhancing brain lesions after endovascular treatment of aneurysms.

Complications of endovascular therapy of aneurysms mainly include aneurysm rupture and thromboembolic events. The widespread use of MR imaging for follow-up of these patients revealed various nonvascular complications such as aseptic meningitis, hydrocephalus, and perianeurysmal brain edema. We present 7 patients from 5 different institutions that developed MR imaging-enhancing brain lesions after endovascular therapy of aneurysms, detected after a median time of 63 days. The number of lesions ranged from 4-46 (median of 10.5), sized 2-20 mm, and were mostly in the same vascular territory used for access. Three patients presented with symptoms attributable to these lesions. After a median follow-up of 21.5 months, the number of lesions increased in 2, was stable in 1, decreased in 3, and disappeared in 1. The imaging and clinical characteristics suggested a foreign body reaction. We could find no correlation to a specific device, but a possible source may be the generic hydrophilic coating.

Use of flow-diverting devices in fusiform vertebrobasilar giant aneurysms: a report on periprocedural course and long-term follow-up.

BACKGROUND AND PURPOSE: Fusiform vertebrobasilar giant aneurysms are a rare (<1% of all intracranial aneurysms) but challenging aneurysm subtype. Little data are available on the natural history of this aneurysm subtype and the impact of the use of flow-diverting stents on the long-term clinical and imaging follow-up. In this article, we present our experience with the treatment of fusiform vertebrobasilar giant aneurysms by flow diverting stents. We aim to stimulate a discussion of the best management paradigm for this challenging aneurysm subtype. MATERIALS AND METHODS: We retrospectively identified 6 patients with fusiform vertebrobasilar giant aneurysms who had been treated with flow-diverting stents between October 2009 and March 2012 in our center. The available data were re-evaluated. The modified Rankin Scale score was assessed before intervention, during the stay in hospital, and at discharge. RESULTS: Six patients were identified (all male; age range, 49-71 years; median age, 60 years). Handling of material was successful in all cases. No primary periprocedural complications occurred. The mean follow-up was 13 months (15 days to 29 months). During follow-up, 3 of 6 patients had recurrent cerebral infarctions, but no patient experienced SAH. Two patients presented with acute thrombotic stent occlusion. The modified Rankin Scale score was not higher than 3 in any of the cases before intervention, whereas the best mRS score at the last follow-up was 5. Four of 6 patients died during follow-up. CONCLUSIONS: Endovascular treatment of fusiform vertebrobasilar giant aneurysms with flow-diverting devices is feasible from a technical point of view; however, changes in hemodynamics with secondary thrombosis are not predictable. We currently do not intend to treat fusiform vertebrobasilar giant aneurysms with flow-diverting devices until we have further understanding of the pathophysiology, natural history, and hemodynamic effects of flow diversion.

WEB-DL endovascular treatment of wide-neck bifurcation aneurysms: short- and midterm results in a European study.

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.

Update on acute endovascular and surgical stroke treatment.

Emergency stroke care has become a natural part of the emerging discipline of neurocritical care and demands close cooperation between the neurologist and neurointerventionists, neurosurgeons, and anesthesiologists. Endovascular treatment (EVT), including intra-arterial thrombolysis, mechanical thrombectomy and angioplasty/stenting, is under rapid development. Although EVT has yet to be shown in randomized controlled trials to improve clinical outcome compared to intravenous thrombolysis, it is far better in achieving recanalization of occluded large cerebral vessels, which is crucial for rescuing the penumbra. Moreover, decompressive craniectomy is now a well-established treatment option for malignant middle cerebral artery infarction and cerebellar stroke. Using a case-based approach, this article reviews recent achievements in advanced treatment options for patients with acute ischemic stroke.

Serial stereotactic biopsy of brainstem lesions in adults improves diagnostic accuracy compared with MRI only.

OBJECTIVE: The aim of the current prospective study was to analyse the validity of MRI based diagnosis of brainstem gliomas which was verified by stereotactic biopsy and follow-up evaluation as well as to assess prognostic factors and risk profile. METHODS: Between 1998 and 2007, all consecutive adult patients with radiologically suspected brainstem glioma were included. The MRI based diagnosis of the lesions was made independently by an experienced neuroradiologist. Histopathological evaluation was performed in all patients from paraffin embedded specimens obtained by multimodal image guided stereotactic serial biopsy technique. Histopathological results were compared with prior radiological assessment. Length of survival was estimated with the Kaplan-Meier method and prognostic factors were calculated using the Cox model. RESULTS: 46 adult patients were included. Histological evaluation revealed pilocytic astrocytoma (n = 2), WHO grade II glioma (n = 14), malignant glioma (n = 12), metastasis (n = 7), lymphoma (n = 5), cavernoma (n = 1), inflammatory disease (n = 2) or no tumour/gliosis (n = 3). Perioperative morbidity was 2.5% (n = 1). There was no permanent morbidity and no mortality. All patients with "no tumour" or "inflammatory disease" survived. Patients with low grade glioma and malignant glioma showed a 1 year survival rate of 75% and 25%, respectively; the 1 year survival rate for patients with lymphoma or metastasis was 30%. In the subgroup with a verified brainstem glioma, negative predictors for length of survival were higher tumour grade (p = 0.002) and Karnofsky performance score < or =70 (p = 0.004). CONCLUSION: Intra-axial brainstem lesions with a radiological pattern of glioma represent a very heterogeneous tumour group with completely different outcomes. Radiological features alone are not reliable for diagnostic classification. Stereotactic biopsy is a safe method to obtain a valid tissue diagnosis, which is indispensible for treatment decision.

Structural and functional MRIs disclose cerebellar pathologies in idiopathic downbeat nystagmus.

BACKGROUND: Neurologic disorders in which the etiology and pathogenesis are not yet understood are termed idiopathic. Downbeat nystagmus (DBN) is a frequent eye movement disorder that clinically manifests with oscillopsia and postural instability. Forty percent of patients with DBN are classified as having idiopathic DBN, because no underlying pathology can be demonstrated by conventional MRI or laboratory tests. METHODS: We evaluated gray matter brain volumes of 11 patients with idiopathic DBN and compared them to those of healthy controls using voxel-based morphometry. In a second, functional MRI experiment, patients and controls performed downward smooth pursuit eye movements (DOWN), which were then compared with straight-ahead fixation of a stationary target (MID). RESULTS: Small areas of localized gray matter atrophy were detected in the lateral cerebellar hemispheres (lobule VI) and ocular motor vermis of patients with idiopathic DBN, but not in the flocculus and paraflocculus. The functional imaging data, however, revealed reduced activation in the parafloccular lobule and in the ponto-medullary brainstem of the patients when they performed smooth pursuit eye movements downwards. CONCLUSIONS: The applied specialized imaging and data analysis techniques disclosed pathologies in an idiopathic eye movement disorder. The focal atrophy found in the vermal and lateral cerebellar regions in downbeat nystagmus (DBN) may lead to deficits in smooth pursuit eye movement initiation, which in turn causes hypofunction of the parafloccular lobe, associated with DBN. Our data are in line with experiments in primates showing that ablation of the floccular and parafloccular lobes disrupts smooth pursuit and causes DBN.

Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL.

OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy caused by mutations of the Notch3 gene. The disease is characterized by T2-hyperintense lesions (subcortical white matter lesions), T1-hypointense lesions (lacunar lesions), and T2*-weighted gradient-echo (GE) lesions (cerebral microhemorrhages [CMs]) visualized on clinical MRI sequences and is considered as a model of "pure" subcortical ischemic vascular dementia. Although numerous studies have investigated the impact of white matter lesions in patients with CADASIL, the clinical importance of lacunar lesions remains unknown. Our purpose was to examine the influence of the visible MRI markers in the disease, including the load of lacunar lesions on cognitive impairment and disability in CADASIL. METHODS: We collected clinical data from 147 consecutive patients enrolled in an ongoing two-center prospective cohort study. Degree of disability was assessed by modified Rankin scale and Barthel index. Degree of cognitive impairment was assessed by Mattis Dementia Rating Scale and Mini-Mental Status Examination. T1-weighted, fluid-attenuated inversion recovery, and GE images were obtained on a 1.5-T MRI. Volume and location of lacunar lesions, white matter hyperintensities (WMHs), and CMs were assessed. RESULTS: There was a significant independent association between age, volume of lacunar lesions, and global cognitive function scales when analyzed in a multivariable model. In contrast, WMHs and CMs had no independent influence on cognitive function. Disability in this cohort was associated with volume of lacunar lesions, CMs, systolic blood pressure, and age but not with WMHs. CONCLUSIONS: Among the lesions observed on conventional MRI in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the overall lacunar lesion burden seems to have the most important impact on cognitive function and disability. These findings suggest that preventive strategies to decrease the risk of lacunar lesions as observed on MRI may reduce disease-related impairment in CADASIL. These results suggest that lacunar lesions may also play a key role in disability and cognitive impairment in more common forms of small-vessel disease.

Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease causing stroke and subcortical vascular dementia. Recent studies in sporadic subcortical ischemic vascular disease have drawn attention to brain atrophy as a clinically important marker of disease progression. However, little is known about the role of brain atrophy and its clinical correlates in CADASIL. METHOD: The authors determined the normalized brain volume (NBV) and percent brain volume change (PBVC) over 2 years in 76 CADASIL subjects (45.1 +/- 9.7 years) using the SIENA (structural image evaluation using normalization of atrophy) software and its adaptation for cross-sectional measurements (SIENAX). Baseline assessments included systolic blood pressure (SBP), homocysteine levels, BMI, and APOE genotyping. T2-lesion volumes and clinical scales were assessed at both time points. RESULTS: The NBV significantly correlated with all clinical scores (Rankin, NIH Stroke Scale, Barthel, structured interview for the diagnosis of Alzheimer dementia and multi-infarct dementia, Mattis dementia rating scale) at both time points independently of age and sex. PBVC correlated with changes of all clinical scores (all p < 0.01) except for the Mattis dementia rating scale (p = 0.10). In a linear regression model, age (p < 0.001), male sex (p < 0.01), and SBP (p = 0.07) were the main risk factors for a lower NBV at baseline. Age (p < 0.001) and SBP (p = 0.01) were risk factors for brain volume loss during follow-up. Sample size estimates showed that the number of individuals needed to demonstrate a treatment effect in a trial can be reduced when PBVC is used as an endpoint. CONCLUSIONS: This study identifies brain atrophy as an important aspect of the disease process in CADASIL and establishes significant correlations with multiple clinical aspects including cognition. Age and systolic blood pressure are risk factors for brain volume loss during follow-up. Percent brain volume change seems promising as an adjunct outcome measure in future interventional trials.

O-(2-[18F]fluoroethyl)-L-tyrosine PET for monitoring the effects of convection-enhanced delivery of paclitaxel in patients with recurrent glioblastoma.

PURPOSE: Convection-enhanced delivery (CED) of paclitaxel is a new locoregional approach for patients with recurrent glioblastoma. The aim of this study was to evaluate O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) in monitoring the effects of this type of direct drug delivery. METHODS: Eight patients with recurrent glioblastoma underwent CED of paclitaxel, which was infused over stereotactically placed catheters into the tumour. FET PET and MRI were performed before and 4 weeks after therapy and then at 3-month intervals to document follow-up. For quantitative evaluation, SUV(max)(tumour)/SUV(mean)(background) ratios were calculated. RESULTS: At baseline all tumours showed gadolinium enhancement and high FET uptake (SUV(max)/BG 3.2+/-0.8). Four weeks after CED, a statistically significant decrease in FET uptake was seen (SUV(max)/BG-17%; p<0.01). During follow-up, no recurrence was observed within the CED area. Two out of eight patients with extended tumours died 4 and 5 months after treatment, most probably from local complications. Temporarily stable disease with stable FET uptake was observed in six of eight patients; this was followed by progression and increasing FET uptake ratios (+46%) distant from the CED area in five of the six patients 3-13 months after CED. One patient still presents stable FET uptake 10 months after CED. MRI showed unchanged/increasing contrast enhancement and oedema without ability to reliably assess disease progression. CONCLUSION: FET PET is a valuable tool in monitoring the effects of CED of paclitaxel. In long-term follow-up, stable or decreasing FET uptake, even in contrast-enhancing lesions, is suggestive of reactive changes, whereas increasing ratios appear always to be indicative of recurrence. Therefore, FET PET is more reliable than MRI in differentiating stable disease from tumour regrowth.

Neuronavigation based on CT angiography for surgery of intracranial aneurysms: primary experience with unruptured aneurysms.

Several reports have demonstrated the use of three-dimensional (3D) computed tomographic angiography (CTA) for preoperative planning in patients with intracranial aneurysms. Until now, there are no reports on the potential role of navigation systems in combination with CTA in aneurysm surgery. In the present study we report our experience with neuronavigation based on CTA in 16 patients with unruptured anterior circulation aneurysms for 1) planning craniotomy; 2) guided approach to the aneurysm; and 3) 3D presentation of the aneurysm and adjacent arteries in correct orientation. The reconstructed CTA images were analyzed preoperatively with regard to diameter of aneurysm neck and dome as well as projection and possible daughter aneurysms, and these parameters were compared with the intraoperative findings. In addition the accuracy of the navigator to locate the aneurysm neck was measured intraoperatively. Navigated approach planning resulted in variable keyhole craniotomies for the 7 middle cerebral artery aneurysms, but did not result in deviation from small standard craniotomies for the internal carotid and anterior communicating artery aneurysms. Precision of the indication of the navigator with regard to the aneurysm neck ranged from < 1 mm to 4 mm. Intraoperative assessment confirmed the CTA data with regard to aneurysm size and projection in all, and definition of daughter aneurysms and adjacent arteries in most cases. The computer assisted approach allowed a smaller, exactly placed craniotomy primarily in MCA aneurysms. 3D presentation of the aneurysms and the adjacent arteries in correct orientation facilitated identification and dissection the aneurysms. Current navigation systems are not precise enough to allow "blind" aneurysm clipping by placing a real clip on the virtual aneurysm neck.