Omid Nikoubashman

Thalamus pathology in multiple sclerosis: from biology to clinical application

There is a broad consensus that MS represents more than an inflammatory disease: it harbors several characteristic aspects of a classical neurodegenerative disorder, i.e. damage to axons, synapses and nerve cell bodies. While the clinician is equipped with appropriate tools to dampen peripheral cell recruitment and, thus, is able to prevent immune-cell driven relapses, effective therapeutic options to prevent the simultaneously progressing neurodegeneration are still missing. Furthermore, while several sophisticated paraclinical methods exist to monitor the inflammatory-driven aspects of the disease, techniques to monitor progression of early neurodegeneration are still in their infancy and have not been convincingly validated. In this review article, we aim to elaborate why the thalamus with its multiple reciprocal connections is sensitive to pathological processes occurring in different brain regions, thus acting as a “barometer” for diffuse brain parenchymal damage in MS. The thalamus might be, thus, an ideal region of interest to test the effectiveness of new neuroprotective MS drugs. Especially, we will address underlying pathological mechanisms operant during thalamus degeneration in MS, such as trans-neuronal or Wallerian degeneration. Furthermore, we aim at giving an overview about different paraclinical methods used to estimate the extent of thalamic pathology in MS patients, and we discuss their limitations. Finally, thalamus involvement in different MS animal models will be described, and their relevance for the design of preclinical trials elaborated.

High mutation detection rates in cerebral cavernous malformation upon stringent inclusion criteria: one-third of probands are minors.

Cerebral cavernous malformations (CCM) are prevalent vascular malformations occurring in familial autosomal dominantly inherited or isolated forms. Once CCM are diagnosed by magnetic resonance imaging, the indication for genetic testing requires either a positive family history of cavernous lesions or clinical symptoms such as chronic headaches, epilepsy, neurological deficits, and hemorrhagic stroke or the occurrence of multiple lesions in an isolated case. Following these inclusion criteria, the mutation detection rates in a consecutive series of 105 probands were 87% for familial and 57% for isolated cases. Thirty‐one novel mutations were identified with a slight shift towards proportionally more CCM3 mutations carriers than previously published (CCM1: 60%, CCM2: 18%, CCM3: 22%). In‐frame deletions and exonic missense variants requiring functional analyses to establish their pathogenicity were rare: An in‐frame deletion within the C‐terminal FERM domain of CCM1 resulted in decreased protein expression and impaired binding to the transmembrane protein heart of glass (HEG1). Notably, 20% of index cases carrying a CCM mutation were below age 10 and 33% below age 18 when referred for genetic testing. Since fulminant disease courses during the first years of life were observed in CCM1 and CCM3 mutation carriers, predictive testing of minor siblings became an issue.

Radiation dose reduction in perfusion CT imaging of the brain: A review of the literature

Perfusion CT (PCT) of the brain is widely used in the settings of acute ischemic stroke and vasospasm monitoring. The high radiation dose associated with PCT is a central topic and has been a focus of interest for many researchers. Many studies have examined the effect of radiation dose reduction in PCT using different approaches. Reduction of tube current and tube voltage can be efficient and lead to a remarkable reduction of effective radiation dose while preserving acceptable image quality. The use of novel noise reduction techniques such as iterative reconstruction or spatiotemporal smoothing can produce sufficient image quality from low-dose perfusion protocols. Reduction of sampling frequency of perfusion images has only little potential to reduce radiation dose. In the present article we aimed to summarize the available data on radiation dose reduction in PCT imaging of the brain.

Neurothrombectomy in acute ischaemic stroke: a prospective single‐centre study and comparison with randomized controlled trials

In the last few months five multicentre, randomized controlled trials (RCTs) unequivocally showed the superiority of mechanical thrombectomy in large vessel occlusion acute ischaemic stroke compared to systemic thrombolysis. Despite varying inclusion criteria and time intervals from onset to revascularization overall increases of good functional outcome between 55% and 81% were reported. However, only a minority of screened patients (approximately 1%) were eligible for intra‐arterial (IA) therapy.

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.

Active push deployment technique improves stent/vessel-wall interaction in endovascular treatment of acute stroke with stent retrievers.

Background The optimal interaction between stent struts and thrombus is crucial for successful revascularization in endovascular stroke therapy with stent retrievers. Deploying the stent retriever by actively pushing it into the thrombus increases the radial force with which the stent struts expand into the thrombus. Objective To examine the active push deployment (APD) technique in an in vitro model and present our clinical experience with this technique. Methods In an in vitro experiment we investigated the configuration of a Solitaire and a Trevo ProVue device (both 4×20 mm), depending on whether the devices were deployed using the APD technique or simple unsheathing. We retrospectively assessed the effectiveness and safety of this technique by analyzing 130 patients with large vessel occlusions (carotid T or M1 segment of the middle cerebral artery), who received endovascular treatment with a Trevo device (4×20 mm) that was deployed using the APD technique. Results In vitro experiment: the APD technique improved apposition of the devices to the vessel wall. There was widening of 30% (Trevo) and 19% (Solitaire) at the cost of a shortening of 5% and 4%, respectively, when the devices were deployed in a carotid T model. Clinical study: the revascularization rate (Thrombolysis in Cerebral Infarction ≥2b) with the Trevo device was 90%. There were no retriever-associated dissections or perforations in 278 retrieval maneuvers. Conclusions The APD technique improves apposition of the tested devices to the vessel wall. The widening effect comes at the cost of minimal shortening of the devices. Our clinical experience shows that using the APD technique to deploy the Trevo device is effective and safe.

Optimizing endovascular stroke treatment: removing the microcatheter before clot retrieval with stent-retrievers increases aspiration flow.

Background Flow control during endovascular stroke treatment with stent-retrievers is crucial for successful revascularization. The standard technique recommended by stent-retriever manufacturers implies obstruction of the respective access catheter by the microcatheter, through which the stent-retriever is delivered. This, in turn, results in reduced aspiration during thrombectomy. In order to maximize aspiration, we fully retract the microcatheter out of the access catheter before thrombectomy—an approach we term the ‘bare wire thrombectomy’ (BWT) technique. We verified the improved throughput with systematic in vitro studies and assessed the clinical effectiveness and safety of this method. Methods We compared aspiration flow of water through various access catheters (5–8 F) with a Rebar microcatheter (0.18 inch and 0.27 inch) and a Trevo stent-retriever using the standard technique and the BWT technique in vitro. We also retrospectively analyzed 302 retrieval maneuvers in 117 patients who received endovascular treatment with a stent-retriever between February 2010 and April 2015. Results In the in vitro experiment, removal of the microcatheter in all tested settings resulted in significantly increased aspiration flow through the access catheter (p<0.001). This effect was particularly pronounced in access catheters with a diameter of ≤7 F. In the clinical study, the revascularization rate (Thrombolysis In Cerebral Infarction ≥2b) was 91%. There were no complications associated with the BWT technique in 302 retrieval maneuvers. Conclusions The BWT technique results in improved aspiration flow rates compared with the standard deployment technique. Our clinical data show that the BWT technique is effective and safe.

Metal artifact reduction for flat panel detector intravenous CT angiography in patients with intracranial metallic implants after endovascular and surgical treatment

Background Flat panel detector CT angiography with intravenous contrast agent injection (IV CTA) allows high-resolution imaging of cerebrovascular structures. Artifacts caused by metallic implants like platinum coils or clips lead to degradation of image quality and are a significant problem. Objective To evaluate the influence of a prototype metal artifact reduction (MAR) algorithm on image quality in patients with intracranial metallic implants. Methods Flat panel detector CT after intravenous application of 80 mL contrast agent was performed with an angiography system (Artis zee; Siemens, Forchheim, Germany) using a 20 s rotation protocol (200° rotation angle, 20 s acquisition time, 496 projections). The data before and after MAR of 26 patients with a total of 34 implants (coils, clips, stents) were independently evaluated by two blinded neuroradiologists. Results MAR improved the assessability of the brain parenchyma and small vessels (diameter <1 mm) in the neighborhood of metallic implants and at a distance of 6 cm (p<0.001 each, Wilcoxon test). Furthermore, MAR significantly improved the assessability of parent vessel patency and potential aneurysm remnants (p<0.005 each, McNemar test). MAR, however, did not improve assessability of stented vessels. Conclusions When an intravenous contrast protocol is used, MAR significantly ameliorates the assessability of brain parenchyma, vessels, and treated aneurysms in patients with intracranial coils or clips.

Retrieval of Migrated Coils with Stent Retrievers: An Animal Study

BACKGROUND AND PURPOSE: Coil migration is a potentially serious complication of endovascular aneurysm treatment. The aim of the study was to systematically investigate the effectiveness of coil retrieval with a stent retriever in an animal model. MATERIALS AND METHODS: A total of 148 coils of various types and sizes were placed into arteries of varying diameters in a porcine in vivo model. Coil retrieval was performed by placing a Trevo ProVue stent retriever over the coil and trying to trap a part of the platinum coil within the stent mesh by advancing the microcatheter over the stent or simply by retrieving the stent without trying to trap the coil by advancing the microcatheter. RESULTS: Coil retrieval was successful in 101 of 102 cases (99%), in which trapping of the coil within the stent retriever by advancing the microcathter was applied. When we only pulled back the stent without trapping the coil, retrieval was successful in only 5 of 46 cases (11%). Coil type, coil structure (2D versus 3D), actual coil shape in the affected vessel, investigator experience, aspiration, coil localization, and vessel diameter had no significant influence on retrieval outcome. There was no case of vessel perforation. CONCLUSIONS: Retrieval of migrated platinum coils with a stent retriever is an effective treatment option for migrated coils when the correct technique is applied.

Clinical Impact of Ventilation Duration in Patients with Stroke Undergoing Interventional Treatment under General Anesthesia: The Shorter the Better?

The authors investigated the impact of early extubation and ventilation duration in a cohort of 103 patients that underwent thrombectomy under general anesthesia. Prolonged ventilation was associated with pneumonia during hospitalization and unfavorable functional outcome (mRS greater than or equal to 3) and death at follow-up. According to ROC analysis, a cutoff after 24 hours predicted unfavorable functional outcome with a sensitivity and specificity of 60% and 78%, respectively. The authors conclude that short ventilation times are associated with a lower pneumonia rate and more favorable clinical outcome. BACKGROUND AND PURPOSE: Whether general anesthesia for neurothrombectomy in patients with ischemic stroke has a negative impact on clinical outcome is currently under discussion. We investigated the impact of early extubation and ventilation duration in a cohort that underwent thrombectomy under general anesthesia. MATERIALS AND METHODS: We analyzed 103 consecutive patients from a prospective stroke registry. They met the following criteria: CTA-proved large-vessel occlusion in the anterior circulation, ASPECTS above 6 on presenting cranial CT, revascularization by thrombectomy with the patient under general anesthesia within 6 hours after onset of symptoms, and available functional outcome (mRS) 90 days after onset. RESULTS: The mean ventilation time was 128.07 ± 265.51 hours (median, 18.5 hours; range, 1–1244.7 hours). Prolonged ventilation was associated with pneumonia during hospitalization and unfavorable functional outcome (mRS ≥3) and death at follow-up (Mann-Whitney U test; P ≤ .001). According to receiver operating characteristic analysis, a cutoff after 24 hours predicted unfavorable functional outcome with a sensitivity and specificity of 60% and 78%, respectively. Our results imply that delayed extubation was not associated with a less favorable clinical outcome compared with immediate extubation after the procedure. CONCLUSIONS: Short ventilation times are associated with a lower pneumonia rate and more favorable clinical outcome. Cautious interpretation of our data implies that whether patients are extubated immediately after the procedure is irrelevant for clinical outcome as long as ventilation does not exceed 24 hours.