Thrombectomy in large vessel occlusion stroke-Does age matter?

OBJECTIVES: Endovascular treatment (EVT) is the gold standard treatment for emergent large vessel occlusion (LVO). The benefit of EVT for emergent LVO in elderly patients (>80 years old) is still debated as they have been under-represented in randomized controlled trials. Elderly patients with an emergent LVO are a growing population warranting further study. MATERIALS & METHODS: We included 225 consecutive patients treated with EVT for LVO either in the anterior or posterior circulation. The clinical outcome was assessed using the National Institute of Health Stroke Scale (NIHSS). Long-term functional outcome was assessed using 90-day modified ranking scale (mRS). RESULTS: Neurological improvement: A five-year higher age predicted a 0.43 higher mean NIHSS score after EVT (p = .027). After adjusting for confounders (influencing variables), the association between age and post-interventional NIHSS was reduced and non-significant (p = .17). At discharge, a five-year higher age predicted a 0.74 higher mean NIHSS (p = .003). After adjusting for confounders this association was reduced and non-significant (p = .06). Long-term functional outcome: A five-year higher age predicted a 0.20 higher mRS at three months (p < .001). When adjusting for confounders this number was reduced to 0.16, yet still highly significant (p < .001). CONCLUSIONS: Age seems to have a minor role in predicting neurological improvement after EVT but has an impact on long-term functional outcome. The decision to perform or withhold EVT should therefore not solely be based on age.

Improving Stroke Care in Times of the COVID-19 Pandemic Through Simulation: Practice Your Protocols!

During the coronavirus disease 2019 (COVID-19) pandemic, infectious disease control is of utmost importance in acute stroke treatment. This is a new situation for most stroke teams that often leads to uncertainty among physicians, nurses, and technicians who are in immediate contact with patients. The situation is made even more complicated by numerous new regulations and protocols that are released in rapid succession. Herein, we are describing our experience with simulation training for COVID-19 stroke treatment protocols. One week of simulation training allowed us to identify numerous latent safety threats and to adjust our institution-specific protocols to mitigate them. It also helped our physicians and nurses to practice relevant tasks and behavioral patterns (eg, proper donning and doffing PPE, where to dispose potentially contaminated equipment) to minimize their infectious exposure and to adapt to the new situation. We therefore strongly encourage other hospitals to adopt simulation training to prepare their medical teams for code strokes during the COVID-19 pandemic.

Endovascular thrombectomy at low-volume centres: A Bayesian solution.

PURPOSE: Endovascular treatment (EVT) is traditionally performed by neurointerventional radiologists at tertiary medical centres imposing long transport ways to large vessel occlusion (LVO) stroke patients in rural areas. The purpose of this study is to evaluate the technical and clinical results over time at Stavanger University Hospital, a hospital without neurointerventional expertise, where trained general interventional radiologist performs EVT. METHODS: All patients with LVO stroke treated with EVT from May 2009 to December 2018 were included in the analysis. Technical outcome was measured by the modified treatment in cerebral ischaemia (mTICI) score, functional outcome by the modified Rankin Scale (mRS), complications registered. RESULTS: A total of 235 patients were treated with EVT. An angiographically good result (mTICI 2b or 3) could be seen in 66.7% of the patients treated the first year. In 2011, the year EVT with stent retrievers was introduced, the recanalization rate rose to 81.8%, and from 2014 onwards, it was stable around 80%. After introduction of aspiration together with stent retrievers in 2012, a good functional outcome (mRS 0-2) was obtained in >40% of the treated patients. In 2018, 61.1% of the patients got a good functional outcome. CONCLUSIONS: Endovascular treatment of LVO stroke performed by general vascular interventional radiologist in close collaboration with diagnostic neuroradiologists and stroke neurologists can achieve technical revascularization results and clinical patient outcomes in line with international recommendations, and the randomized controlled studies performed. This approach may help to introduce EVT in geographical areas where this service is lacking due to the absence of neurointerventional specialists.

Clinical outcomes and safety profile of Tenecteplase in wake-up stroke.

BACKGROUND: Tenecteplase has probably pharmacological and clinical advantages in the treatment of acute ischemic stroke. There are lacking data about safety and efficacy of tenecteplase in wake-up stroke (WUPS). AIMS: To investigate safety and efficacy of tenecteplase compared to alteplase in WUPS patients included in NOR-TEST. METHODS: WUPS patients in NOR-TEST were included in the study based on DWI-FLAIR mismatch. Included patients randomly assigned (1:1) to receive intravenous tenecteplase 0.4 mg/kg (to a maximum of 40 mg) or alteplase 0.9 mg/kg (to a maximum of 90 mg). Neurological improvement was defined as 1) favorable functional outcome at 90 days modified Rankin Scale (mRS) of 0 or 1 and 2) neurological improvement measured with the National Institutes of Health Stroke Scale (NIHSS) of 4 points within 24 hours as compared to admission NIHSS or NIHSS 0 at 24 hours. RESULTS: Of 1100 patients from 13 stroke centers included in NOR-TEST, 45 were WUPS patients. Of these, 5 patients were stroke mimics and excluded. Of the remaining 40 patients (3.6%), 24 were treated with alteplase (60%). There was no difference in the number of patients achieving a good clinical outcome (mRS 0-1) in either treatment group. Patients treated with tenecteplase showed a better early neurological improvement (87.5% vs 54.2%, P = 0.027). No ICH was detected on MRI/CT 24-28 hours after thrombolysis. CONCLUSIONS: In WUPS patients treated in NOR-TEST, there was no difference in clinical outcomes at 90 days and no ICH events or deaths were observed in either alteplase- or tenecteplase-treated patients. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01949948.

Endovascular Thrombectomy in the Elderly: Do Radiological and Clinical Outcomes Differ from Those in Younger Patients? A Prospective Single-Center Experience.

OBJECTIVES: Endovascular treatment (EVT) has emerged as the gold standard therapy for stroke due to large vessel occlusion (LVO). There is however limited evidence to suggest that similar efficacy can be expected in elderly patients. We aimed to assess the efficacy and safety of EVT in elderly patients (aged > 80), comparing outcomes to younger patients (aged < 80). MATERIAL AND METHODS: A total of 195 patients with LVO stroke treated with EVT were included and dichotomized by age. We compared neurological improvement, clinical 90 day outcome, technical recanalization rates, procedure-related complications, and mortality in between the groups. RESULTS: Both groups showed equally marked neurological improvement. A favorable outcome modified Rankin Scale (mRS < 2) was seen in 28% of the elderly patients compared to 46% of the younger patients (p = 0.01). mRS 0-3 was seen in 46% of the elderly patients and 58% of the younger patients (p = 0.09). The rates of successful technical recanalization did not differ between the groups and there were no differences in procedural complication rates or incidence of symptomatic intracranial bleeding. Three-month mortality rates were however higher in the elderly group. CONCLUSIONS: EVT in the elderly resulted in equally notable neurological improvement as compared to younger patients. Although the elderly had a higher mortality rate and fewer favorable clinical outcomes at 3 month follow-up, a strict upper age limit for EVT seems unjustified.

The Norwegian tenecteplase stroke trial (NOR-TEST): randomised controlled trial of tenecteplase vs. alteplase in acute ischaemic stroke.

BACKGROUND: Alteplase is the only approved thrombolytic agent for acute ischaemic stroke. The overall benefit from alteplase is substantial, but some evidence indicates that alteplase also has negative effects on the ischaemic brain. Tenecteplase may be more effective and less harmfull than alteplase, but large randomised controlled phase 3 trials are lacking. The Norwegian Tenecteplase Stroke Trial (NOR-TEST) aims to compare efficacy and safety of tenecteplase vs. alteplase. METHODS/DESIGN: NOR-TEST is a multi-centre PROBE (prospective randomised, open-label, blinded endpoint) trial designed to establish superiority of tenecteplase 0.4 mg/kg (single bolus) as compared with alteplase 0.9 mg/kg (10% bolus + 90% infusion/60 minutes) for consecutively admitted patients with acute ischaemic stroke eligible for thrombolytic therapy, i.e. patients a) admitted <4½ hours after symptoms onset; b) admitted <4½ hours after awakening with stroke symptoms c) receiving bridging therapy before embolectomy.Randomisation tenecteplase:alteplase is 1:1. The primary study endpoint is favourable functional outcome defined as modified Rankin Scale 0-1 at 90 days. Secondary study endpoints are: 1) haemorrhagic transformation (haemorrhagic infarct/haematoma); 2) symptomatic cerebral haemorrhage on CT 24-48 hours; 3) major neurological improvement at 24 hours; 4) recanalisation at 24-36 hours; 5) death. DISCUSSION: NOR-TEST may establish a novel approach to acute ischaemic stroke treatment. A positive result will lead to a more effective, safer and easier treatment for all acute ischaemic stroke pasients.NOR-TEST is reviewed and approved by the Regional Committee for Medical and Health Research Ethics (2011/2435), and The Norwegian Medicines Agency (12/01402). NOR-TEST is registered with EudraCT No 2011-005793-33 and in ClinicalTrials.gov (NCT01949948).

Cerebrospinal fluid Aß levels correlate with structural brain changes in Parkinson's disease.

ParkWest is a large Norwegian multicenter study of newly diagnosed drug-naïve subjects with Parkinson's disease (PD). Cognitively normal PD subjects (PDCN) and PD subjects with mild cognitive impairment (PDMCI) from this cohort have significant hippocampal atrophy and ventricular enlargement, compared to normal controls. Here, we aimed to investigate whether the same structural changes are associated with cerebrospinal fluid (CSF) levels of amyloid beta (Aß)38 , Aß40 , Aß42 , total tau (t-tau), and phosphorylated tau (p-tau). We performed three-dimensional radial distance analyses of the hippocampi and lateral ventricles using the MRI data from ParkWest subjects who provided CSF at baseline. Our sample consisted of 73 PDCN and 18 PDMCI subjects. We found significant associations between levels of all three CSF Aß analytes and t-tau and lateral ventricular enlargement in the pooled sample. In the PDCN sample, all three amyloid analytes showed significant associations with the radial distance of the occipital and frontal horns of the lateral ventricles. CSF Aß38 and Aß42 showed negative associations, with enlargement in occipital and frontal horns of the lateral ventricles in the pooled sample, and a negative association with the occipital horns in PDMCI. CSF Aß levels in early PD correlate with ventricular enlargement, previously associated with PD dementia. Therefore, CSF and MRI markers may help identify PD patients at high risk for developing cognitive decline and dementia in the course of their illness. Contrary to Alzheimer's disease, we found no associations between CSF t-tau and p-tau and hippocampal atrophy.

Metric based virtual simulation training for endovascular thrombectomy improves interventional neuroradiologists' simulator performance.

OBJECTIVE: Metric based virtual reality simulation training may enhance the capability of interventional neuroradiologists (INR) to perform endovascular thrombectomy. As pilot for a national simulation study we examined the feasibility and utility of simulated endovascular thrombectomy procedures on a virtual reality (VR) simulator. METHODS: Six INR and four residents participated in the thrombectomy skill training on a VR simulator (Mentice VIST 5G). Two different case-scenarios were defined as benchmark-cases, performed before and after VR simulator training. INR performing endovascular thrombectomy clinically were also asked to fill out a questionnaire analyzing their degree of expectation and general attitude towards VR simulator training. RESULTS: All participants improved in mean total procedure time for both benchmark-cases. Experts showed significant improvements in handling errors (case 2), a reduction in contrast volume used (case 1 and 2), and fluoroscopy time (case 1 and 2). Novices showed a significant improvement in steps finished (case 2), a reduction in fluoroscopy time (case 1), and radiation used (case 1). Both, before and after having performed simulation training the participating INR had a positive attitude towards VR simulation training. CONCLUSION: VR simulation training enhances the capability of INR to perform endovascular thrombectomy on the VR simulator. INR have generally a positive attitude towards VR simulation training. Whether the VR simulation training translates to enhanced clinical performance will be evaluated in the ongoing Norwegian national simulation study.

Cost-effectiveness of a quality improvement project, including simulation-based training, on reducing door-to-needle times in stroke thrombolysis.

BACKGROUND: Rapid revascularisation in acute ischaemic stroke is crucial to reduce its total burden including societal costs. A quality improvement (QI) project that included streamlining the stroke care pathway and simulation-based training was followed by a significant reduction in median door-to-needle time (27 to 13 min) and improved patient outcomes after stroke thrombolysis at our centre. Here, we present a retrospective cost-effectiveness analysis of the QI project. METHODS: Costs for implementing and sustaining QI were assessed using recognised frameworks for economic evaluations. Effectiveness was calculated from previously published outcome measures. Cost-effectiveness was presented as incremental cost-effectiveness ratios including costs per minute door-to-needle time reduction per patient, and costs per averted death in the 13-month post-intervention period. We also estimated incremental cost-effectiveness ratios for a projected 5-year post-intervention period and for varying numbers of patients treated with thrombolysis. Furthermore, we performed a sensitivity analysis including and excluding costs of unpaid time. RESULTS: All costs including fixed costs for implementing the QI project totalled US$44 802, while monthly costs were US$2141. We calculated a mean reduction in door-to-needle time of 13.1 min per patient and 6.36 annual averted deaths. Across different scenarios, the estimated costs per minute reduction in door-to-needle time per patient ranged from US$13 to US$29, and the estimated costs per averted death ranged from US$4679 to US$10 543. CONCLUSIONS: We have shown that a QI project aiming to improve stroke thrombolysis treatment at our centre can be implemented and sustained at a relatively low cost with increasing cost-effectiveness over time. Our work builds on the emerging theory and practice for economic evaluations in QI projects and simulation-based training. The presented cost-effectiveness data might help guide healthcare leaders planning similar interventions.

Simulation-based team-training in acute stroke: Is it safe to speed up?

BACKGROUND: In acute ischemic stroke (AIS), rapid treatment with intravenous thrombolysis (IVT) is crucial for good clinical outcome. Weekly simulation-based team-training of the stroke treatment team was implemented, resulting in faster treatment times. The aim of this study was to assess whether this time reduction led to a higher proportion of stroke mimics (SMs) among patients who received IVT for presumed AIS, and whether these SM patients were harmed by intracranial hemorrhage (ICH). METHODS: All suspected AIS patients treated with IVT between January 1, 2015 and December 31, 2020 were prospectively registered. In 2017, weekly in situ simulation-based team-training involving the whole stroke treatment team was introduced. To analyze possible unintended effects of simulation training, the proportion of SMs among patients who received IVT for presumed AIS were identified by clinical and radiological evaluation. Additionally, we identified the extent of symptomatic ICH (sICH) in IVT-treated SM patients. RESULTS: From 2015 to 2020, 959 patients were treated with IVT for symptoms of AIS. After introduction of simulation training, the proportion of patients treated with IVT who were later diagnosed as SMs increased significantly (15.9% vs. 24.4%, p = .003). There were no ICH complications in the SM patients treated before, whereas two SM patients suffered from asymptomatic ICH after introduction of simulation training (p = 1.0). When subgrouping SMs into prespecified categories, only the group diagnosed with peripheral vertigo increased significantly (2.5% vs. 8.6%, p < .001). CONCLUSIONS: Simulation training of the acute stroke treatment team was associated with an increase in the proportion of patients treated with IVT for a suspected AIS who were later diagnosed with peripheral vertigo. The proportion of other SM groups among IVT-treated patients did not change significantly. No sICH was detected in IVT-treated SM patients.

Time-Based Decision Making for Reperfusion in Acute Ischemic Stroke.

Decision making in the extended time windows for acute ischemic stroke can be a complex and time-consuming process. The process of making the clinical decision to treat has been compounded by the availability of different imaging modalities. In the setting of acute ischemic stroke, time is of the essence and chances of a good outcome diminish by each passing minute. Navigating the plethora of advanced imaging modalities means that treatment in some cases can be inefficaciously delayed. Time delays and individually based non-programmed decision making can prove challenging for clinicians. Visual aids can assist such decision making aimed at simplifying the use of advanced imaging. Flow charts are one such visual tool that can expedite treatment in this setting. A systematic review of existing literature around imaging modalities based on site of occlusion and time from onset can be used to aid decision making; a more program-based thought process. The use of an acute reperfusion flow chart helping navigate the myriad of imaging modalities can aid the effective treatment of patients.

The role of APOE alleles in incident Parkinson's disease. The Norwegian ParkWest Study.

OBJECTIVES: Apolipoprotein E (APOE) gene alleles have been associated with various neurodegenerative disorders. However, there have been conflicting reports on associations between APOE alleles and Parkinson's disease (PD) and age at onset in PD. There exist no data on APOE alleles in an unselected cohort of patients with incident PD. PATIENTS AND METHODS: To determine the role of APOE alleles in PD and age of onset in PD at time of diagnosis, 203 patients with incident PD and 187 healthy control subjects from Western and Southern Norway were investigated according to their APOE allele status. RESULTS: No association was observed between any APOE alleles and susceptibility to PD or age at onset in PD. CONCLUSION: In our cohort of unselected, incident PD patients APOE alleles do not seem to play a role for development of PD. Prospective, long-term follow-up may still reveal associations between APOE alleles and clinical and neuropsychological progression in PD.

Headache and MRI Changes after Endovascular Treatment of a Cerebral Aneurysm.

BACKGROUND: The main complications after endovascular therapy of intracranial aneurysms are aneurysm rupture and thromboembolic events. Yet, the widespread use of magnetic resonance imaging (MRI) in follow-up of these patients also demonstrates other, rarely known complications such as aseptic meningitis and foreign body reaction. CASE PRESENTATION: A small aneurysm in the right posterior communicating artery was treated with endovascular therapy in a 65 year old woman. Two weeks after successful interventional treatment, the patient developed a headache. On MRI performed five months after intervention, vasogenic edema was seen in the vascular territory of the right internal carotid artery. The edema and the symptoms diminished without specific treatment within a year. INTERPRETATION: The clinical and radiological presentation of this case are suggestive of a foreign body reaction, a treatable condition that radiologists and clinicians should be aware of.

Word deafness as a cortical auditory processing deficit: a case report with MEG.

Pure word deafness is a rare disorder dramatically impairing comprehension of spoken language, while auditory functions remain relatively intact. We present a 71-year-old woman with a slowly progressive disturbance of speech perception due to pure word deafness. MRI revealed degeneration of the temporal lobes. A magnetoencephalographic investigation using alternating single tone stimulation showed that N100 was followed by a second transient response and was abnormally prolonged up to 600-700 ms. We conclude that auditory processing is disturbed at long latency ranges following the N100, which may result in the clinical presentation of pure word deafness.

The golden hour of acute ischemic stroke.

BACKGROUND: Acute Ischemic Stroke (AIS) treatment has been revolutionised in the last two decades with the increasing use of Intravenous Thrombolysis (IVT) and with the advent of Endovascular therapy (EVT). AIS treatment and outcome are time dependant and time saving measures are being implemented at every step of the treatment chain. These changes have resulted in lower treatment times in-hospital, but it is unclear if this translates into more patients being treated within 60 min of symptom onset - the Golden Hour. The clinical outcome of IVT therapy in this patient group was our secondary outcome. METHODS: From 2009 onwards, systematic changes were made to the AIS treatment chain leading to a dramatic decrease in Door-to-Needle (DTN) time. Analyses were performed on the number of these treatments year on year and their clinical outcomes within the Golden Hour at Stavanger University Hospital (SUS). RESULTS: Six-hundred and thirteen patients were included; seventy-three were treated within the Golden Hour. The percentage of total IVT treatments occurring in the Golden Hour rose from 2.2% in 2009 to 14.5% in 2015 (p = 0.006) with a high of 18.3% in 2012 (p < 0.001). All of these patients had a Median NIHSS of 0 at discharge, irrespective of age and pre-existing comorbidity. There was no incidence of any ICH and in-hospital mortality was only 2.7% in this group. DISCUSSION: The time from AIS symptom onset to treatment is filled with delays. Despite the inherence of some delays,significant efforts on the part of the pre- and in- hospital treatment chain have made IVT therapy within 60 min a possibility. The allocation and use of resources in the setting of rapid AIS treatment is warrantedand yields unprecedented results. CONCLUSIONS: Our study shows that improved treatment routines led to an increase in the number of patients treated within the Golden Hour. Treatment in the Golden Hour leads to excellent outcomes in all patients, irrespective of age and pre-existing comorbidity.

Endovascular stroke treatment in a small-volume stroke center.

INTRODUCTION: Our purpose was to evaluate the safety and efficacy of endovascular treatment (EVT) of stroke caused by large vessel occlusions (LVO) performed by general interventional radiologists in cooperation with stroke neurologists and neuroradiologists at a center with a limited annual number of procedures. We aimed to compare our results with those previously reported from larger stroke centers. PATIENTS AND METHODS: A total of 108 patients with acute stroke due to LVO treated with EVT were included. Outcome was measured using the modified Rankin scale (mRS) at 90 days. Efficacy was classified according to the modified thrombolysis in cerebral infarction (mTICI) scoring system. Safety was evaluated according to the incidence of procedural complications and symptomatic intracranial hemorrhage (sICH). RESULTS: Mean age of the patients was 67.5 years. The median National Institutes of Health Stroke Scale (NIHSS) on hospital admission was 17. Successful revascularization was achieved in 76%. 39.4% experienced a good clinical outcome (mRS<3). Intraprocedural complications were seen in 7.4%. 7.4% suffered a sICH. 21.3% died within 3 months after EVT. DISCUSSION: The use of general interventional radiologists in EVT of LVO may be a possible approach for improving EVT coverage where availability of specialized neurointerventionalists is challenging. EVT for LVO stroke performed by general interventional radiologists in close cooperation with diagnostic neuroradiologists and stroke neurologists can be safe and efficacious despite the low number of annual procedures.