Hamed Asadi

Diffusion Tensor Imaging in Huntington’s disease reveals distinct patterns of white matter degeneration associated with motor and cognitive deficits

White matter (WM) degeneration is an important feature of Huntington’s disease (HD) neuropathology. To investigate WM degeneration we used Diffusion Tensor Imaging and Tract-Based Spatial Statistics to compare Fractional Anisotropy, Mean Diffusivity (MD), parallel diffusivity and perpendicular diffusivity (λ⊥) in WM throughout the whole brain in 17 clinically diagnosed HD patients and 16 matched controls. Significant WM diffusivity abnormalities were identified primarily in the corpus callosum (CC) and external/extreme capsules in HD patients compared to controls. Significant correlations were observed between motor symptoms and MD in the CC body, and between global cognitive impairment and λ⊥ in the CC genu. Probabilistic tractography from these regions revealed degeneration of functionally relevant interhemispheric WM tracts. Our findings suggest that WM degeneration within interhemispheric pathways plays an important role in the deterioration of cognitive and motor function in HD patients, and that improved understanding of WM pathology early in the disease is required.

A longitudinal diffusion tensor imaging study in symptomatic Huntington's disease

Objective The striatum and its projections are thought to be the earliest sites of Huntingtons disease (HD) pathology. This study aimed to investigate progression of striatal pathology in symptomatic HD using diffusion tensor imaging. Method Diffusion weighted images were acquired in 18 HD patients and in 17 healthy controls twice, 1 year apart. Mean diffusivity (MD) was calculated in the caudate, putamen, thalamus and corpus callosum, and compared between groups. In addition, caudate width was measured using T1 high resolution images and correlated with caudate MD. Correlation analyses were also performed in HD between caudate/putamen MD and clinical measures. Results MD was significantly higher in the caudate and putamen bilaterally for patients compared with controls at both time points although there were no significant MD differences in the thalamus or corpus callosum. For both groups, MD did not change significantly in any region from baseline to year 1. There was a significant negative correlation between caudate width and MD in patients at baseline but no correlation between these parameters in controls. There was also a significant negative correlation between Mini-Mental State Examination scores and caudate MD and putamen MD at both time points in HD. Conclusions It appears that microstructural changes influence cognitive status in HD. Although MD was significantly higher in HD compared with controls at both time points, there were no longitudinal changes in either group. This finding does not rule out the possibility that MD could be a sensitive biomarker for detecting early change in preclinical HD.

Machine learning for outcome prediction of acute ischemic stroke post intra-arterial therapy.

Introduction Stroke is a major cause of death and disability. Accurately predicting stroke outcome from a set of predictive variables may identify high-risk patients and guide treatment approaches, leading to decreased morbidity. Logistic regression models allow for the identification and validation of predictive variables. However, advanced machine learning algorithms offer an alternative, in particular, for large-scale multi-institutional data, with the advantage of easily incorporating newly available data to improve prediction performance. Our aim was to design and compare different machine learning methods, capable of predicting the outcome of endovascular intervention in acute anterior circulation ischaemic stroke. Method We conducted a retrospective study of a prospectively collected database of acute ischaemic stroke treated by endovascular intervention. Using SPSS®, MATLAB®, and Rapidminer®, classical statistics as well as artificial neural network and support vector algorithms were applied to design a supervised machine capable of classifying these predictors into potential good and poor outcomes. These algorithms were trained, validated and tested using randomly divided data. Results We included 107 consecutive acute anterior circulation ischaemic stroke patients treated by endovascular technique. Sixty-six were male and the mean age of 65.3. All the available demographic, procedural and clinical factors were included into the models. The final confusion matrix of the neural network, demonstrated an overall congruency of ∼80% between the target and output classes, with favourable receiving operative characteristics. However, after optimisation, the support vector machine had a relatively better performance, with a root mean squared error of 2.064 (SD: ±0.408). Discussion We showed promising accuracy of outcome prediction, using supervised machine learning algorithms, with potential for incorporation of larger multicenter datasets, likely further improving prediction. Finally, we propose that a robust machine learning system can potentially optimise the selection process for endovascular versus medical treatment in the management of acute stroke.

Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke

BACKGROUND Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin‐specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. METHODS We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. RESULTS Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90‐day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. CONCLUSIONS Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND‐IA TNK ClinicalTrials.gov number, NCT02388061.)

Advances in Medical Revascularisation Treatments in Acute Ischemic Stroke

Urgent reperfusion of the ischaemic brain is the aim of stroke treatment and there has been ongoing research to find a drug that can promote vessel recanalisation more completely and with less side effects. In this review article, the major studies which have validated the use and safety of tPA are discussed. The safety and efficacy of other thrombolytic and anticoagulative agents such as tenecteplase, desmoteplase, ancrod, tirofiban, abciximab, eptifibatide, and argatroban are also reviewed. Tenecteplase and desmoteplase are both plasminogen activators with higher fibrin affinity and longer half-life compared to alteplase. They have shown greater reperfusion rates and improved functional outcomes in preliminary studies. Argatroban is a direct thrombin inhibitor used as an adjunct to intravenous tPA and showed higher rates of complete recanalisation in the ARTTS study with further studies which are now ongoing. Adjuvant thrombolysis techniques using transcranial ultrasound are also being investigated and have shown higher rates of complete recanalisation, for example, in the CLOTBUST study. Overall, development in medical therapies for stroke is important due to the ease of administration compared to endovascular treatments, and the new treatments such as tenecteplase, desmoteplase, and adjuvant sonothrombolysis are showing promising results and await further large-scale clinical trials.

Advances in endovascular treatment of acute ischaemic stroke

Over the past decade, there have been rapid advancements in ischaemic stroke reperfusion treatments. However, clear clinical benefit is yet to be shown in large clinical trials. In this review, the major studies in different types of endovascular treatments including intra‐arterial thrombolysis, aspiration devices, mechanical clot retrievers and the new stent retrievers are discussed. First‐generation mechanical thrombectomy devices such as the MERCI Retriever (Stryker, Kalamazoo, MI, USA) and Penumbra aspiration device (Penumbra Inc., Alameda, CA, USA) demonstrated safety and higher rates of recanalisation in the MERCI and Penumbra Pivotal Stroke Trial; however, there was no significant improvement in clinical outcome. Second‐generation endovascular stent retrieval devices Solitaire (ev3 Neurovascular, Irvine, CA, USA) and Trevo (Stryker) have shown promising results. In preliminary trials, SOLITAIRE with the Intention for Thrombectomy (SWIFT) and Thrombectomy Revascularization of Large Vessel Occlusions (TREVO), both showed rates of recanalisation close to 90% and significantly improved clinical outcomes compared with the MERCI study, but the recent landmark studies for endovascular treatment (Interventional Management of Stroke (IMS III), Mechanical Retrieval and Recanalisation of Stroke Clots Using Embolectomy (MR‐RESCUE) and SYNTHESIS) did not show any clinical benefit from endovascular treatment compared with standard intravenous therapy. However, moving forward, the recent Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands (MR‐CLEAN) study results have shown marked improvements in recanalisation, reperfusion and functional outcome in patients receiving endovascular treatment (97% using stent retrievers) within 6 h in addition to standard medical care. Overall, although evidence regarding the efficacy of endovascular treatment in acute stroke has been equivocal, recent publications of large multicentre randomised controlled trials indicate benefit of intra‐arterial stent retriever reperfusion in patients selected by appropriate imaging and treated early by experienced operators, and it will likely remain an important adjunct to established medical treatment with intravenous tPA.

Changing Management of Acute Ischaemic Stroke: the New Treatments and Emerging Role of Endovascular Therapy.

Opinion statementUrgent reperfusion of the ischaemic brain is the aim of stroke treatment, and the last two decades have seen a rapid advancement in the medical and endovascular treatment of acute ischaemic stroke. Intravenous tissue plasminogen activator (tPA) was first introduced as a safe and effective thrombolytic agent followed by the introduction of newer thrombolytic agents as well as anticoagulant and antiplatelet agents, proposed as potentially safer drugs with more favourable interaction profiles. In addition to chemo-thrombolysis, other techniques including transcranial sonothrombolysis and microbubble cavitation have been introduced which are showing promising results, but await large-scale clinical trials. These developments in medical therapies which are undoubtedly of great importance due to their potential widespread and immediate availability are paralleled with gradual but steady improvements in endovascular recanalisation techniques which were initiated by the introduction of the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) and Penumbra systems. The introduction of the Solitaire device was a significant achievement in reliable and safe endovascular recanalisation and was followed by further innovative stent retrievers. Initial trials failed to show a solid benefit in endovascular intervention compared with IV-tPA alone. These counterintuitive results did not last long, however, when a series of very well-designed randomised controlled trials, pioneered by MR-CLEAN, EXTEND-IA and ESCAPE, emerged, confirming the well-believed daily anecdotal evidence. There have now been seven positive trials of endovascular treatment for acute ischaemic stroke. Now that level I evidence regarding the superiority of endovascular recanalisation is abundantly available, the clinical challenge is how to select patients suitable for intervention and to familiarise and educate stroke care providers with this recent development in stroke care. It is important for the interventional services to be provided only in comprehensive stroke centres and endovascular interventions attempted by experienced well-trained operators, at this stage as an adjunct to the established medical treatment of IV-tPA, if there are no contraindications.

Systematic Review and Single-Center Experience for Endovascular Management of Visceral and Renal Artery Aneurysms

PURPOSE To report a systematic review of endovascular management of visceral and renal artery aneurysms (VRAA) and results at a tertiary referral center. MATERIALS AND METHODS A literature review was performed via a comprehensive electronic search of PubMed, MEDLINE, EMBASE, and Cochrane databases, followed by retrospective analysis of all VRAAs treated at a tertiary referral center from January 1999 to December 2015. RESULTS The systematic review included 22 studies published between 2005 and 2016 describing endovascular treatment of VRAA. In the systematic review cohort, 646 aneurysms (432 true, 151 false, 63 unclassified) were treated using endovascular methods with 93.2% technical success, 99.3% visceral preservation, 3.5% major complication (classified based on Society of Interventional Radiology criteria), 1.5% 30-day periprocedural mortality, and 4.6% reintervention rates. In the local cohort, 19 aneurysms (12 true, 7 false) were treated with 100% technical success, 94.7% visceral preservation, and 10.5% major complication rates. There was no periprocedural mortality. Over mean follow-up of 31.9 months (range, 2-170 months), there were 2 aneurysm reperfusions, which required no further treatment. Results incorporating data from the systematic review and local cohorts (665 aneurysms) showed 93.6% technical success, 99.1% visceral preservation, 3.7% major complication, 1.5% periprocedural mortality, and 4.4% reintervention rates. CONCLUSIONS Endovascular treatment of VRAA is associated with excellent technical success and visceral preservation rates. Major complication and periprocedural mortality rates are comparatively low. A few VRAA (4.4%) required future reintervention suggesting that imaging follow-up is essential after initial treatment.

Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study

Background and hypothesis Intravenous thrombolysis with alteplase remains standard care prior to thrombectomy for eligible patients within 4.5 h of ischemic stroke onset. However, alteplase only succeeds in reperfusing large vessel arterial occlusion prior to thrombectomy in a minority of patients. We hypothesized that tenecteplase is non-inferior to alteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy. Study design EXTEND-IA TNK is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint non-inferiority study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale≤3 (no upper age limit), large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal computed tomography and absence of contraindications to intravenous thrombolysis. Patients are randomized to either IV alteplase (0.9 mg/kg, max 90 mg) or tenecteplase (0.25 mg/kg, max 25 mg) prior to thrombectomy. Study outcomes The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified treatment in cerebral infarction 2 b/3 or the absence of retrievable thrombus. Secondary outcomes include modified Rankin Scale at day 90 and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. Trial registration ClinicalTrials.gov NCT02388061

Endovascular Therapy Research in Lower Limb Peripheral Arterial Disease Published Over a 5-Year Period: Who is Publishing and Where?

IntroductionPeripheral arterial disease (PAD) is being increasingly managed by endovascular therapies. In this study, we identified the clinical services publishing research as well as the journals of publication over a 5-year period.MethodsTwenty keywords and phrases related to endovascular intervention were identified, and a literature search was performed through the PubMed database from January 2009 to January 2014. Inclusion criteria were English language, study population more than five patients, and matching the keyword search. Eligible studies were collated into a database and classified by journal of publication, PubMed number, article title, publishing clinical service, type of publication, country of origin, and authors.Results825 studies from 114 different journals were identified. 297 papers were excluded. Of the 528 included papers, 204 (39%) were published by Vascular Surgery (VS), 157 (30%) by Interventional Radiology (IR), 101 (19%) by Cardiology, 43 (8%) by Angiology, 6 (1%) by Vascular Medicine, and 17 (3%) from miscellaneous services. 283 (54%) studies originated from Europe, 157 (30%) from North America, 76 (14%) from Asia, 6 from Australia, 3 each from South America and Africa. IR published the most papers on PAD endovascular intervention in Europe with VS second while this trend was reversed in the USA. The 528 papers were published in 98 different journals with retrospective case series (72%), the majority.ConclusionIR continues to play a significant research role in endovascular intervention in PAD, particularly in Europe, and specifically in below the knee intervention, pedal intervention, and drug-eluting technologies.