Julian Maingard

Future Directions for Intra-Arterial Therapy for Acute Ischaemic Stroke: Is There Life after Three Negative Randomized Controlled Studies

Background: The three randomised controlled trials, Interventional Management of Stroke III (IMS3), Mechanical Retrieval and Revascularization of Stroke Clots Using Embolectomy (MR RESCUE) and Synthesis Expanasion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischaemic Stroke (SYNTHESIS EXP) showed no significant difference in clinical outcomes comparing intra-arterial (IA) therapy with intravenous thrombolysis. This article will explore the reasons for failure to show superiority of IA therapy. Summary: There are many reasons for the disappointing results of the three randomised controlled trials. Opposing views on IA therapy exist. Critics argue that only a small percentage of patients will be eligible for IA therapy and that it will never be cost-effective. Additionally, current trials have failed to address superior recanalization rates of new generation devices and lack of patient selection by advanced imaging. Time-to-treatment is longer in these randomised controlled trials and stroke outcomes were worse than anticipated. The current randomised controlled trials also took long periods to complete. There is emerging evidence that general anesthetic negatively influences outcome. Next generation trials will attempt to address these issues. Key Messages: There are disparate explanations for the disappointing results from the three IA therapy randomized controlled studies. Poor recanalisation rates with first generation endovascular devices, lack of advanced neuroimaging to aid in patient selection, lack of data surrounding the use of general anaesthesia, and prolonged time-to-treatment are potential contributors to negative results. The new generation of trials has the potential of addressing these pressing issues.

Endovascular Thrombectomy Alone versus Combined with Intravenous Thrombolysis

BACKGROUNDnTo date, no randomized trial has directly addressed the question of whether intravenous (IV) tissue plasminogen activator (tPA) improves outcomes in IV tPA-eligible patients who will eventually undergo endovascular therapy (EVT), or whether a direct EVT strategy is equally effective. We performed a systematic review and meta-analysis to compare the efficacy and safety of direct EVT versus endovascular treatment with IV tPA (EVT+IV tPA) in adults with acute ischemic stroke.nnnMETHODSnWe performed electronic searches of 6 databases from their inception to January 2017. Data were extracted and analyzed according to predefined clinical endpoints.nnnRESULTSnTwelve comparative studies, comprising 1275 patients in the EVT-only arm and 1340 patients in the combined EVT+IV tPA arm, were included. The rates of good functional outcomes (modified Rankin Scale score ≤2) and 90-day mortality were not statistically significantly different between the EVT and EVT+IV tPA arms (44% vs. 48%; odds ratio [OR], 0.80; 95% confidence interval [CI], 0.64-1.002; Pxa0= 0.052 and 20.4% vs. 19.4%, OR 1.19; 95% CI, 0.83-1.71; Pxa0= 0.34, respectively). The rate of symptomatic intracranial hemorrhage also was not significantly different between the EVT and EVT+IV tPA arms (3.7% vs. 3.8%; OR, 0.98; 95% CI, 0.65-1.48; Pxa0= 0.91). There were no between-group differences in the rates of other complications.nnnCONCLUSIONSnNo significant differences between the 2 groups were found in terms of favorable functional outcome, mortality rate, or complications based on contemporary endovascular therapies.

Combined Vertebral Augmentation and Radiofrequency Ablation in the Management of Spinal Metastases: an Update

Opinion statementSpinal metastases are the most commonly encountered tumour of the spine, occurring in up to 40% of patients with cancer. Each year, approximately 5% of cancer patients will develop spinal metastases. This number is expected to increase as the life expectancy of cancer patients increases. Patients with spinal metastases experience severe and frequently debilitating pain, which often decreases their remaining quality of life. With a median survival of less than 1xa0year, the goals of treatment in spinal metastases are reducing pain, improving or maintaining level of function and providing mechanical stability. Currently, conventional treatment strategies involve a combination of analgesics, bisphosphonates, radiotherapy and/or relatively extensive surgery. Despite these measures, pain management in patients with spinal metastases is often suboptimal. In the last two decades, minimally invasive percutaneous interventional radiology techniques such as vertebral augmentation and radiofrequency ablation (RFA) have shown progressive success in reducing pain and improving function in many patients with symptomatic spinal metastases. Both vertebral augmentation and RFA are increasingly being recognised as excellent alternative to medical and surgical management in carefully selected patients with spinal metastases, namely those with severe refractory pain limiting daily activities and stable pathological vertebral compression fractures. In addition, for more complicated lesions such as spinal metastasis with soft tissue extension, combined treatments such as vertebral augmentation in conjunction with RFA may be helpful. While combined RFA and vertebral augmentation have theoretical benefits, comparative trials have not been performed to establish superiority of combined therapy. We believe that a multidisciplinary approach as well as careful pre-procedure evaluation and imaging will be necessary for effective and safe management of spinal metastases. RFA and vertebral augmentation should be considered during early stages of the disease so as to maintain the remaining quality of life in this patient population group.

Vertebroplasty and Kyphoplasty for Osteoporotic Vertebral Fractures: What Are the Latest Data?

SUMMARY: Osteoporotic vertebral compression fractures frequently result in significant morbidity and health care resource use. For patients with severe and disabling pain, vertebral augmentation (vertebroplasty and kyphoplasty) is often considered. Although vertebroplasty was introduced >30 years ago, there are conflicting opinions regarding the role of these procedures in the treatment of osteoporotic vertebral compression fractures. This review article updates clinicians on the published prospective randomized controlled data, including the most recent positive trials that followed initial negative trials in 2009. Analysis of multiple national claim datasets has also provided further insight into the utility of these procedures. Finally, we considered the recent recommendations of national organizations and medical societies that advise on the use of vertebral augmentation procedures for osteoporotic vertebral compression fractures.

‘Donut’ basilar aneurysm with brainstem compression: Treatment using a flow diverting stent

Partially thrombosed aneurysms with circular flow dynamics around central thrombus pose a therapeutic dilema. We demonstrate the successful treatment of a patient with a large basilar donut aneurysm with a flow diverting stent without the use of embolisation coils in order to obviate the risk of further brainstem compression.

Primary angiitis of the central nervous system presenting as a mass lesion

We report a 51-year-old Asian man with primary angiitis of the central nervous system (PACNS) with atypical presentation as a mass lesion. PACNS is an uncommon condition causing inflammation and destruction of the blood vessels of the central nervous system. The aetiology is unclear and multiple mechanisms have been proposed. Its incidence is estimated at 2.4 per million per year, affecting patients of all ages (median 50 years) and more commonly Caucasian men. In Australia, 12 patients fulfilled the diagnostic criteria for PACNS between 1998 and 2009 at The Royal Melbourne Hospital, a university-affiliated tertiary referral centre. The accurate and timely diagnosis of PACNS is very challenging due to disease mimicry and the absence of specific serological tests. This patient illustrates additional diagnostic difficulty with his atypical PACNS presentation as a mass lesion.

Cervical CT scan-guided epidural blood patches for spontaneous intracranial hypotension.

We describe two patients with spontaneous intracranial hypotension (SIH), presenting with postural headache due to C1-C2 cerebrospinal fluid (CSF) leak. Both patients were refractory to lumbar epidural blood patching (EBP), and subsequently underwent successful CT scan-guided cervical EBP. SIH affects approximately 1 in 50,000 patients, with females more frequently affected. Its associated features are variable, and as such, misdiagnosis is common. Therefore, imaging plays an important role in the diagnostic workup of SIH and can include MRI of the brain and spine, CT myelogram, and radionuclide cisternography. In patients with an established diagnosis and confirmed CSF leak, symptoms will usually resolve with conservative management. However, in a select subgroup of patients, the symptoms are refractory to medical management and require more invasive therapies. In patients with cervical leaks, EBP in the cervical region is an effective management approach, either in close proximity to, or directly targeting a dural defect. CT scan-guided cervical EBP is an effective treatment approach in refractory SIH, and should be considered in those patients who are refractory to conservative management.

Endovascular mechanical thrombectomy in large-vessel occlusion ischemic stroke presenting with low national institutes of health stroke scale: systematic review and meta-analysis

INTRODUCTIONnMechanical thrombectomy has become the standard of care for management of most large vessel occlusion (LVO) strokes. When patients with LVO present with minor stroke symptomatology, no consensus on the role of mechanical thrombectomy exists.nnnMETHODSnA systematic review and meta-analysis were performed to identify studies that focused on mechanical thrombectomy, either as a standalone treatment or with intravenous tissue plasminogen activator (IV tPA), in patients with mild strokes with LVO, defined as a baseline National Institutes of Health Stroke Scale score ≤5 at presentation. Data on methodology, quality criteria, and outcome measures were extracted, and outcomes were compared using odds ratio as a summary statistic.nnnRESULTSnFive studies met the selection criteria and were included. When compared with medical therapy without IV tPA, mechanical thrombectomy and medical therapy with IV tPA were associated with improved 90-day modified Rankin Scale (mRS) score. Among medical patients who were not eligible for IV tPA, those who underwent mechanical thrombectomy were more likely to experience good 90-day mRS than those who were not. There was no significant difference in functional outcome between mechanical thrombectomy and medical therapy with IV tPA, and no treatment subgroup was associated with intracranial hemorrhage or death.nnnCONCLUSIONSnIn patients with mild strokes due to LVO, mechanical thrombectomy and medical therapy with IV tPA led to better 90-day functional outcome. Mechanical thrombectomy plays an important role in the management of these patients, particularly in those not eligible for IV tPA.

The 100 most cited articles in the endovascular management of intracranial aneurysms

Introduction Endovascular interventions for intracranial aneurysms have evolved substantially over the past several decades. A citation rank list is used to measure the scientific and/or clinical impact of an article. Our objective was to identify and analyze the characteristics of the 100 most cited articles in the field of endovascular therapy for intracranial aneurysms. Methods We performed a retrospective bibliometric analysis between July and August 2017. Articles were searched on the Science Citation Index Expanded database using Web of Science in order to identify the most cited articles in the endovascular therapy of intracranial aneurysms since 1945. Using selected key terms (‘intracranial aneurysm’, ‘aneurysm’, ‘aneurysmal subarachnoid’, ‘endovascular’, ‘coiling’, ‘stent-assisted’, ‘balloon-assisted’, ‘flow-diversion’) yielded a total of 16u2009314 articles. The top 100 articles were identified and analyzed to extract relevant information, including citation count, authorship, article type, subject matter, institution, country of origin, and year of publication. Results Citations for the top 100 articles ranged from 133 to 1832. All articles were cited an average of 27 times per year. There were 45 prospective studies, including 7 level–II randomized controlled trials. Most articles were published in the 2000s (n=53), and the majority constituted level III or level IV evidence. Half of the top 100 articles arose from the USA. Conclusion This study provides a comprehensive overview of the most cited articles in the endovascular management of intracranial aneurysms. It recognizes the contributions made by key authors and institutions, providing an important framework to an enhanced understanding of the evidence behind the endovascular treatment of aneurysms.

Borderline Alberta Stroke Programme Early CT score patients with acute ischemic stroke due to large vessel occlusion may find benefit with endovascular thrombectomy

OBJECTIVEnSelection of patients with acute ischemic stroke for endovascular thrombectomy (EVT) is complex and time-critical. Benefits of EVT are well established for patients with small core infarcts. The aim of this study was to compare clinical outcomes of EVT in patients with larger established infarcts (Alberta Stroke Programme Early CT Score [ASPECTS] ≤6) with patients with smaller infarcts (ASPECTS 7-10).nnnMETHODSnThe study included 355 patients with acute ischemic stroke due to large vessel occlusion who underwent EVT. ASPECTS was assigned to baseline noncontrast computed tomography, and collateral perfusion scores were assigned to multiphase computed tomography angiography. Baseline stroke severity, collateral grading, and clinical outcome data (complication rate, symptomatic intracranial hemorrhage and 90-day modified Rankin Scale score) were compared between patients with borderline (≤6) and high (7-10) ASPECTS.nnnRESULTSnThere were 34 (10%) patients with borderline ASPECTS. There was no difference in rate of good clinical outcome (37% vs. 46%, Pxa0= 0.852), symptomatic intracerebral hemorrhage (9% vs. 9%, Pxa0= 0.984), or mortality (20% vs. 22%, Pxa0= 0.818) between patients with borderline ASPECTS and high ASPECTS at 90 days. Moreover, there was no significant difference in collateral perfusion grade.nnnCONCLUSIONSnThis study identifies similar clinical benefit of EVT in patients with acute large vessel occlusion stroke with borderline ASPECTS and high ASPECTS.