Angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy compared to best medical treatment: One-year interim results of SPACE-2.

BACKGROUND: Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. METHODS: SPACE-2 is a randomized, controlled, multicenter, open study. A major secondary endpoint was the cumulative rate of any stroke (ischemic or hemorrhagic) or death from any cause within 30 days plus an ipsilateral ischemic stroke within one year of follow-up. Safety was assessed as the rate of any stroke and death from any cause within 30 days after CEA or CAS. Protocol changes had to be implemented. The results on the one-year period after treatment are reported. FINDINGS: It was planned to enroll 3550 patients. Due to low recruitment, the enrollment of patients was stopped prematurely after randomization of 513 patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113). The one-year rate of the major secondary endpoint did not significantly differ between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well as rates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-cause mortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of all strokes occurred in the peri-interventional period. Higher albeit statistically non-significant rates of restenosis occurred in the stenting group (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increased stroke rates. INTERPRETATION: The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.

State of Practice: Endovascular Treatment of Acute Aneurysmal SAH in Germany.

BACKGROUND AND PURPOSE: Acute aneurysmal SAH is a severe disease that requires prompt treatment. Endovascular coiling and neurosurgical clipping are established treatment options. Our intention was to determine the state of current practice in acute aneurysmal SAH treatment in Germany, with emphasis on logistic and temporal aspects. MATERIALS AND METHODS: We interviewed 74 German university and nonuniversity hospitals with an anonymous questionnaire comprising 15 questions concerning the practice of treatment and diagnostics of acute aneurysmal SAH at their respective institutions. The response rate was 74% among all institutions (55/74); among university hospitals, 77%; and among nonuniversity hospitals, 72%. RESULTS: The majority of all aneurysms were treated endovascularly (66% of acute aneurysmal SAH, 66% of unruptured aneurysms). Treatment on weekends was provided by 100% of endovascular and 96% of neurosurgical facilities. Average patients with acute aneurysmal SAH were not treated during the night (98%). Seventy percent of endovascular and 78% of neurosurgical treatments were not started later than 8:00 pm. Fifty-three percent of hospitals would not start a same-day diagnostic angiography in acute aneurysmal SAH if treatment was scheduled for the following day. Eighty-two percent of all centers performed DSA after clipping to evaluate the treatment results. CONCLUSIONS: Our survey gives a detailed summary of the current practice of endovascular treatment and related topics in acute aneurysmal SAH in Germany and also reveals considerable changes in practice in comparison with older data.

General Anesthesia Versus Conscious Sedation in Acute Stroke Treatment: The Importance of Head Immobilization.

PURPOSE: While today mechanical thrombectomy is an established treatment option for main branch occlusions in anterior circulation stroke, there is still an ongoing debate on the kind of anesthesia to be preferred. Introducing a simple method for head stabilization, we analyzed safety and duration of endovascular recanalization procedures under general anesthesia (GA) and conscious sedation (CS). METHODS: We retrospectively identified 84 consecutive patients who underwent mechanical thrombectomy owing to acute anterior circulation stroke. Fifty-three were treated under GA and 31 under CS equipped with a standard cervical collar to reduce head movement. We evaluated recanalization results, in-house time to start recanalization, procedure times, technical and clinical complication rates, and conversion rates from CS to GA. RESULTS: Recanalization of mTICI ≥2b was achieved in 80 % under CS and in 81 % under GA. Median in-house time to start recanalization for CS was 60 min (IQR 28; 44-72) and 77 min (IQR 23; 68-91) for GA (P = 0.001). Median procedure time under CS was 35 min (IQR 43; 69-25) and 41 min (IQR 43; 66-23) for GA (P = 0.9). No major complications such as ICH occurred in either group, and no conversions from CS to GA were necessary. CONCLUSION: Mechanical thrombectomy can be performed faster and safely under CS in combination with simple head immobilization using a standard cervical collar.

Polypharmacology of dopamine receptor ligands.

Most neurological diseases have a multifactorial nature and the number of molecular mechanisms discovered as underpinning these diseases is continuously evolving. The old concept of developing selective agents for a single target does not fit with the medical need of most neurological diseases. The development of designed multiple ligands holds great promises and appears as the next step in drug development for the treatment of these multifactorial diseases. Dopamine and its five receptor subtypes are intimately involved in numerous neurological disorders. Dopamine receptor ligands display a high degree of cross interactions with many other targets including G-protein coupled receptors, transporters, enzymes and ion channels. For brain disorders like Parkinsons disease, schizophrenia and depression the dopaminergic system, being intertwined with many other signaling systems, plays a key role in pathogenesis and therapy. The concept of designed multiple ligands and polypharmacology, which perfectly meets the therapeutic needs for these brain disorders, is herein discussed as a general ligand-based concept while focusing on dopaminergic agents and receptor subtypes in particular.

Assessment and treatment planning of lateral intracranial dural arteriovenous fistulas in 3 T MRI and DSA: A detailed analysis under consideration of time-resolved imaging of contrast kinetics (TRICKS) and ce-MRA sequences.

OBJECTIVES: The current gold standard in the assessment of lateral intracranial dural arteriovenous fistulas (LDAVF) is digital subtraction angiography (DSA). However, magnetic resonance imaging (MRI) is a non-invasive emerging tool for the evaluation of such lesions. The aim of our study was to compare the DSA to our 3 T MR-imaging protocol including a highly spatial resolved (ce-MRA) and a temporal resolved ("time-resolved imaging of contrast kinetics", TRICKS) contrast-enhanced MR angiography to evaluate if solely DSA can remain the gold-standard imaging modality for the treatment planning of LDAVF. METHODS: We retrospectively reviewed matched pairs of DSA and 3 T MRI examinations of 24 patients with LDAVF (03/2008-04/2014) by the same list of relevant criteria for an endovascular LDAVF treatment planning. In particular, we determined intermodality agreement for the Cognard classification, the identifeication of arterial feeders, and the detailed assessment of each venous drainage pattern. RESULTS: Intermodality agreement for the Cognard classification was excellent (ĸ = 1.0). Whereas MRI failed in identifying small arterial feeders, it was superior to the DSA in the assessment of the sinus and the venous drainage pattern. CONCLUSIONS: The combination of MRI and DSA is the new gold standard in LDAVF treatment planning. KEY POINTS: • DSA is superior to the MRI in detecting LDAVF arterial feeders. • MRI excellently evaluates the venous side of an LDAVF. • MRI can replace DSA in initial diagnosis and monitoring of LDAVF. • MRI and DSA combined are the new gold standard in LDAVF treatment planning.

Stent Retriever Thrombectomy in Patients Who Are Ineligible for Intravenous Thrombolysis: A Multicenter Retrospective Observational Study.

BACKGROUND AND PURPOSE: Intravenous thrombolysis with rtPA is the standard of care for patients with acute ischemic stroke within 4.5 hours after symptom onset. However, a considerable number of patients are ineligible for IV thrombolysis due to various contraindications. Recent studies have proved the superiority of mechanical thrombectomy for patients with large-vessel occlusions in combination with IV rtPA compared with IV rtPA alone. We aimed to demonstrate the efficacy of mechanical thrombectomy for patients who are ineligible for IV rtPA. MATERIALS AND METHODS: Patients from the stroke registries of 4 dedicated centers who were treated with mechanical thrombectomy from January 2010 to October 2014 were retrospectively evaluated. Inclusion criteria were the following: acute stroke due to proved large-artery occlusion, ineligibility for IV thrombolysis, and a timeframe of ≤4.5 hours between stroke and the start of mechanical thrombectomy. Recanalization success, periprocedural complications, clinical outcome, and hemorrhages were evaluated. RESULTS: One hundred thirty endovascular recanalization procedures were identified. The locations were the following: proximal ICA in 17 (13.1%), terminus ICA in 25 (19.2%), M1 segment in 77 (59.2%), and M2 segment in 11 (8.5%). TICI 2b/3 results were achieved in 101 (77.7%), and an mRS score of 0-2 in 47 patients (37.9%). There was a significant correlation between TICI 2b/3 results and good clinical outcomes (87.2% versus 6.8%; P = .048). A good clinical result was most frequent when recanalization was achieved within 4.5 hours (37/74 = 50% versus 10/50 = 20.0%; P = .001). Symptomatic hemorrhage occurred in 13.1% of patients; mortality was 24.2%. Periprocedural complications were recorded in 10 patients (7.7%). CONCLUSIONS: Mechanical thrombectomy can achieve good clinical outcomes in patients with acute large-artery occlusion ineligible for IV thrombolysis, in particular when recanalization is reached early.

Spectrum and Prevalence of Pathological Intracranial Magnetic Resonance Imaging Findings in Acute Bacterial Meningitis.

PURPOSE: Aim of this study was to determine the spectrum and prevalence of pathological intracranial magnetic resonance imaging (MRI) findings in patients with acute bacterial meningitis. METHODS: We retrospectively identified all consecutive patients with cerebral spinal fluid proven bacterial meningitis who presented at our neurology department between 2007 and 2012. Pathogenic agents and clinical symptoms were noted. MR-examinations were evaluated regarding presence and localization of pathological signal alterations in the different sequences by two neuroradiologists in consensus. RESULTS: A total of 136 patients with purulent bacterial meningitis were identified. In 114 cases the bacterial pathogen agent was proven and in 75 patients an MRI was available. In 62 of the 75 (82.7 %) patients meningitis-associated pathologic imaging findings were evident on MRI. Overall, intraventricular signal alterations, i.e., signs of pyogenic ventriculitis, were present in 41 cases (54.7 %), while sulcal signal changes were found in 22 cases (29.3 %). Intraparenchymatous signal alterations affected the cortex in 15 cases (20 %), and the white matter in 20 patients (26.7 %). The diffusion-weighted imaging and fluid attenuated inversion recovery sequences were most sensitive in the detection of these changes and showed any pathologic findings in 67.6 and 79.6 %, respectively. Patients with streptococcal meningitis showed significantly more often (n = 29 of 34, 85.3 %) intraventricular and/or sulcal diffusion restrictions than patients with meningitis caused by other agents (n = 12 of 37, 32.4 %) (p< 0.0001). CONCLUSION: Pathological MR findings are frequently found in patients with acute bacterial meningitis. Intraventricular diffusion restrictions, i.e., signs of pyogenic ventriculitis, are more often found in patients with streptococcal, especially pneumococcal, infection.

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.

Diffusion tensor imaging of the trigeminal nerve in patients with trigeminal neuralgia due to multiple sclerosis.

INTRODUCTION: Neurovascular compression (NVC) is the most common cause of trigeminal neuralgia (TN), leading to microstructural changes in the affected nerve detectable using diffusion tensor imaging (DTI). But TN may also emerge as a symptom of multiple sclerosis (MS). The aim of this study was to evaluate if patients with MS-related TN feature the same DTI characteristics as patients with TN caused by NVC. METHODS: Twelve patients with MS-related TN, 12 age-matched patients with NVC-related TN, and 12 healthy controls were included. Using 3T-DTI, mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated for each affected and contralateral trigeminal nerve in patients with MS and NVC-related TN as well as healthy controls. Furthermore, presence of NVC was evaluated for patients with TN. RESULTS: There was no significant difference concerning FA or ADC when comparing the affected and the non-affected sides in patients with MS. FA was significantly lower and ADC higher in patients with MS on the TN affected as well as on the non-affected side compared to the non-affected side of patients with idiopathic TN or healthy controls. Likewise, FA was significantly lower on the affected side compared to the non-affected side in patients with idiopathic TN or healthy controls. NVC was evident in 41.7/0% on the affected/contralateral side in MS patients and 100/8% in the patients with NVC-related TN. CONCLUSION: In patients with MS-related TN, DTI reveals microstructural changes within the trigeminal nerve not only on the affected side but also on the clinically non-affected side.