Endovascular thrombectomy and intravenous alteplase in patients with acute ischemic stroke due to large vessel occlusion: A clinical practice guideline.

AIM: Whether or not use of intravenous alteplase in combination with endovascular thrombectomy (EVT) improves outcomes versus EVT alone, for acute stroke patients with large vessel occlusion presenting directly to a comprehensive stroke center, is uncertain. METHODS: Six randomized trials exploring this issue were published, and we synthesized this evidence to inform a rapid guideline based on the Guidelines International Network principles and guided by the GRADE approach. RESULTS: We enlisted an international panel that included 4 patient partners and 1 caregiver, individuals from 6 countries. The panel considered low certainty evidence that EVT alone, relative to EVT with intravenous alteplase, possibly results in a small decrease in the proportion of patients that achieve functional independence and possibly a small increase in mortality. Both effect estimates were downgraded twice due to very serious imprecision. The panel also considered moderate certainty evidence that EVT alone probably decreases symptomatic intracranial hemorrhage, versus EVT with alteplase, and combination therapy was more costly than EVT alone. As a result of the low certainty for improved recovery without impairment and mortality for combination therapy versus EVT alone, and moderate certainty for increased harm with combination therapy, the panel made a weak recommendation in favor of EVT alone for stroke patients eligible for both treatments, and initially presenting directly to a comprehensive stroke center that provides both treatments. CONCLUSIONS: Consistent with this weak recommendation, optimal patient management will likely often include co-treatment with intravenous alteplase, depending on local circumstances and patient presentation.

International controlled study of revascularization and outcomes following COVID-positive mechanical thrombectomy.

BACKGROUND AND PURPOSE: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p < 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates.

Sweet spots of standard and directional leads in patients with refractory essential tremor: white matter pathways associated with maximal tremor improvement.

OBJECTIVE: In patients with essential tremor (ET) treated with standard deep brain stimulation (sDBS) whose ET had progressed and who no longer received optimal benefit from sDBS, directional deep brain stimulation (dDBS) may provide better tremor control. Current steering may provide better coverage of subcortical structures related to tremor control in patients with ET and significant progression without optimal response to sDBS. METHODS: This study included 6 patients with ET initially treated with sDBS whose tremor later progressed and who then underwent reimplantation with dDBS to optimize their tremor control. To investigate the differences in the local effects of sDBS and dDBS, the authors generated the volume of tissue activation (VTA) to calculate the sweet spots associated with the best possible tremor control with no side effects. Then, to investigate the anatomical structures associated with maximal tremor control, the white matter pathways of the posterior subthalamic areas (PSAs) were generated and their involvement with the sDBS and dDBS sweet spots was calculated. RESULTS: Tremor improvement was significantly better with dDBS (68.4%) than with sDBS (48.7%) (p = 0.017). The sDBS sweet spot was located within the ventral intermediate nucleus, whereas the sweet spot of the dDBS was mainly located within the PSA. The sweet spots of both sDBS and dDBS involved a similar portion of the cerebellothalamic pathway. However, the dDBS had greater involvement of the pallidofugal pathways than the sDBS. CONCLUSIONS: In patients with ET treated with sDBS who later had ET progression, dDBS provided better tremor control, which was related to directionality and a more ventral position. The involvement of both the cerebellothalamic and pallidofugal pathways obtained with dDBS is associated with additional improvement over the sDBS.

Characteristics of a COVID-19 Cohort With Large Vessel Occlusion: A Multicenter International Study.

BACKGROUND: The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke. OBJECTIVE: To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort. METHODS: We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020. RESULTS: The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates.

Delayed coil migration into oropharynx following endovascular coiling of a traumatic carotid cavernous fistula: management considerations.

Carotid-cavernous fistulas (CCFs) are abnormal vascular shunts between the carotid artery and the cavernous sinus. A 37-year-old male presented with a traumatic CCF and basal skull fracture extending through the medial wall of the cavernous sinus and sphenoid sinus. The CCF was treated with endovascular coiling. Three months after this procedure, he was found to have coil migration through the traumatic sphenoid defect into the pharynx. He underwent urgent endonasal endoscopic surgery to disconnect and remove the extruded coil. Post-operative coil migration is a rare but serious complication following endovascular treatment of traumatic CCF.

Acute ischaemic stroke associated with SARS-CoV-2 infection in North America.

BACKGROUND: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age >60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p<0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome. CONCLUSION: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality.

Association of Stent-Retriever Characteristics in Establishing Successful Reperfusion During Mechanical Thrombectomy : Results from the ESCAPE-NA1 Trial.

BACKGROUND: Successful reperfusion determines the treatment effect of endovascular thrombectomy. We evaluated stent-retriever characteristics and their relation to reperfusion in the ESCAPE-NA1 trial. METHODS: Independent re-scoring of reperfusion grade for each attempt was conducted. The following characteristics were evaluated: stent-retriever length and diameter, thrombus position within stent-retriever, bypass effect, deployment in the superior or inferior MCA trunk, use of balloon guide catheter and distal access catheter. Primary outcome was successful reperfusion defined as expanded thrombolysis in cerebral infarction (eTICI) 2b-3 per attempt. The secondary outcome was successful reperfusion eTICI 2b-3 after the first attempt. Separate regression models for each stent-retriever characteristic and an exploratory multivariable modeling to test the impact of all characteristics on successful reperfusion were built. RESULTS: Of 1105 patients in the trial, 809 with the stent-retriever use (1241 attempts) were included in the primary analysis. The stent-retriever was used as the first-line approach in 751 attempts. A successful attempt was associated with thrombus position within the proximal or middle third of the stent (OR 2.06; 95% CI: 1.24-3.40 and OR 1.92; 95% CI: 1.16-3.15 compared to the distal third respectively) and with bypass effect (OR 1.7; 95% CI: 1.07-2.72). Thrombus position within the proximal or middle third (OR 2.80; 95% CI: 1.47-5.35 and OR 2.05; 95% CI: 1.09-3.84, respectively) was associated with first-pass eTICI 2b-3 reperfusion. In the exploratory analysis accounting for all characteristics, bypass effect was the only independent predictor of eTICI 2b-3 reperfusion (OR 1.95; 95% CI: 1.10-3.46). CONCLUSION: The presence of bypass effect and thrombus positioning within the proximal and middle third of the stent-retriever were strongly associated with successful reperfusion.

Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke Update 2020.

The 2020 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for the Secondary Prevention of Stroke includes current evidence-based recommendations and expert opinions intended for use by clinicians across a broad range of settings. They provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations address triage, diagnostic testing, lifestyle behaviors, vaping, hypertension, hyperlipidemia, diabetes, atrial fibrillation, other cardiac conditions, antiplatelet and anticoagulant therapies, and carotid and vertebral artery disease. This update of the previous 2017 guideline contains several new or revised recommendations. Recommendations regarding triage and initial assessment of acute transient ischemic attack (TIA) and minor stroke have been simplified, and selected aspects of the etiological stroke workup are revised. Updated treatment recommendations based on new evidence have been made for dual antiplatelet therapy for TIA and minor stroke; anticoagulant therapy for atrial fibrillation; embolic strokes of undetermined source; low-density lipoprotein lowering; hypertriglyceridemia; diabetes treatment; and patent foramen ovale management. A new section has been added to provide practical guidance regarding temporary interruption of antithrombotic therapy for surgical procedures. Cancer-associated ischemic stroke is addressed. A section on virtual care delivery of secondary stroke prevention services in included to highlight a shifting paradigm of care delivery made more urgent by the global pandemic. In addition, where appropriate, sex differences as they pertain to treatments have been addressed. The CSBPR include supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

Alterations in brain morphology by MRI in adults with neurofibromatosis 1.

OBJECTIVE: Neurofibromatosis 1 (NF1) is a rare autosomal dominant disease that causes the dysregulated growth of Schwann cells. Most reported studies of brain morphology in NF1 patients have included only children, and clinical implications of the observed changes later in life remain unclear. In this study, we used MRI to characterize brain morphology in adults with NF1. METHODS: Planar (2D) MRI measurements of 29 intracranial structures were compared in 389 adults with NF1 and 112 age- and sex-matched unaffected control subjects. The 2D measurements were correlated with volumetric (3D) brain measurements in 99 of the adults with NF1 to help interpret the 2D findings. A subset (n = 70) of these NF1 patients also received psychometric testing for attention deficits and IQ and was assessed for clinical severity of NF1 features and neurological problems. Correlation analysis was performed between the MRI measurements and clinical and psychometric features of these patients. RESULTS: Four of nine corpus callosum measurements were significantly greater in adults with NF1 than in sex- and age-matched controls. All seven brainstem measurements were significantly greater in adults with NF1 than in controls. Increased corpus callosum and brainstem 2D morphology were correlated with increased total white matter volume among the NF1 patients. No robust correlations were observed between the 2D size of these structures and clinical or neuropsychometric assessments. CONCLUSION: Our findings are consistent with the hypothesis that dysregulation of brain myelin production is an important manifestation of NF1 in adults.

Age and Acute Ischemic Stroke Outcome in North American Patients With COVID-19.

Background Acute ischemic stroke (AIS) in the context of COVID-19 has received considerable attention for its propensity to affect patients of all ages. We aimed to evaluate the effect of age on functional outcome and mortality following an acute ischemic event. Methods and Results A prospectively maintained database from comprehensive stroke centers in Canada and the United States was analyzed for patients with AIS from March 14 to September 30, 2020 who tested positive for SARS-CoV-2. The primary outcome was Modified Rankin Scale score at discharge, and the secondary outcome was mortality. Baseline characteristics, laboratory values, imaging, and thrombectomy workflow process times were assessed. Among all 126 patients with COVID-19 who were diagnosed with AIS, the median age was 63 years (range, 27-94). There were 35 (27.8%) patients with AIS in the aged ≤55 years group, 47 (37.3%) in the aged 56 to 70 group, and 44 (34.9%) in the aged >70 group. Intravenous tissue plasminogen activator and thrombectomy rates were comparable across these groups, (P=0.331 and 0.212, respectively). There was a significantly lower rate of mortality between each group favoring younger age (21.9% versus 45.0% versus 48.8%, P=0.047). After multivariable adjustment for possible confounders, a 1-year increase in age was significantly associated with fewer instances of a favorable outcome of Modified Rankin Scale 0 to 2 (odds ratio [OR], 0.95; 95 CI%, 0.90-0.99; P=0.048) and higher mortality (OR, 1.06; 95 CI%, 1.02-1.10; P=0.007). Conclusions AIS in the context of COVID-19 affects young patients at much greater rates than pre-pandemic controls. Nevertheless, instances of poor functional outcome and mortality are closely tied to increasing age.

A Single-Center 10-Year Retrospective Analysis of Cryoablation for the Management of Desmoid Tumors.

PURPOSE: To determine the efficacy and safety of cryoablation in patients with desmoid tumors (DTs) retrospectively over a 10-year period at a single institution. MATERIALS AND METHODS: Between February 25, 2010, and February 25, 2020, 25 patients (age, 12-80 years) with 26 lesions (mean preprocedural tumor volume was 237 cm3) were treated over 44 cryoablation procedures. Eleven patients were treated with first-line therapy. Fourteen patients had previous medical therapy, radiotherapy, and/or surgery. Subsequent clinical follow-up, imaging outcomes, and safety were analyzed for technical success, change in total lesion volume (TLV) and viable tumor volume (VTV), modified response evaluation criteria in solid tumors (mRECIST), progression-free survival (PFS) for tumor progression and symptom recurrence, symptom improvement, and procedure-related complications. Symptomatic improvement was defined as documentation of relief of pain (partial or complete) and/or functional impairment. RESULTS: All procedures were technically successful. At 7-12 months, median changes in TLV and VTV were -6.7% (P = .809) and -43.7% (P = .01), respectively. At 10-12 months, the mRECIST responses were complete response, 0%; partial response, 61.5% (8/13); stable disease, 30.8% (4/13); and progressive disease, 7.7% (1/13). The median PFS for tumor progression and symptom recurrence were not reached, with a median follow-up of 15.3 and 21.0 months, respectively. Symptomatic relief (partial or complete) was achieved in 96.9% (32/33) of patients. One major complication was noted (2.4%). CONCLUSIONS: In this retrospectively identified cohort, cryoablation was effective and safe for the local control of extra-abdominal DTs in short-term follow-up.

Directional Deep Brain Stimulation Can Target the Thalamic "Sweet Spot" for Improving Neuropathic Dental Pain.

BACKGROUND: Neuropathic dental pain (NDP) is a chronic pain condition that is notoriously difficult to treat. To date, there are no deep brain stimulation (DBS) studies on this specific pain condition and no optimal target or "sweet spot" has ever been defined. OBJECTIVE: To determine the optimal thalamic target for improving this condition by utilizing the steering abilities of a directional DBS electrode (Vercise CartesiaTM Model DB-2202-45, Boston Scientific). METHODS: A literature search and review of our database identified 3 potential thalamic targets. A directional lead was implanted in a patient with NDP and its current steering used to test the effects in each nucleus. The patient reported her pain after 2 wk of stimulation in a prospective randomized blinded trial of one. Quality of life measurements were performed before and after 3 mo on their best setting. RESULTS: We identified 3 potential nuclei: the centromedian (CM), ventral posterior medial (VPM), and anterior pulvinar. The best results were during VPM stimulation (>90% reduction in pain) and CM stimulation (50% reduction). Following 3 mo of VPM-DBS in combination of lateral CM stimulation, their pain disability index dropped (from 25 to 0) and short form 36 improved (from 67.5 to 90). CONCLUSION: VPM stimulation in combination with CM stimulation is a promising target for NDP. DBS electrode directionality can be used to test multiple targets and select a patient specific "sweet spot" for NDP treatment.

Tremor and Quality of Life in Patients With Advanced Essential Tremor Before and After Replacing Their Standard Deep Brain Stimulation With a Directional System.

OBJECTIVES: Patients with essential tremor treated with thalamic deep brain stimulation may experience increased tremor with the progression of their disease. Initially, this can be counteracted with increased stimulation. Eventually, this may cause unwanted side-effects as the circumferential stimulation from a standard ring contact spreads into adjacent regions. Directional leads may offer a solution to this clinical problem. We aimed to compare the ability of a standard and a directional system to reduce tremor without side-effects and to improve the quality of life for patients with advanced essential tremor. MATERIALS AND METHODS: Six advanced essential tremor patients with bilateral thalamic deep brain stimulation had their standard system replaced with a directional system. Tremor rating scale scores were prospectively evaluated before and after the replacement surgery. Secondary analyses of quality of life related to tremor, voice, and general health were assessed. RESULTS: There was a significantly greater reduction in tremor without side-effects (p = 0.017) when using the directional system. There were improvements in tremor (p = 0.031) and voice (p = 0.037) related quality of life but not in general health for patients using optimized stimulation settings with the directional system compared to the standard system. CONCLUSIONS: In this cohort of advanced essential tremor patients who no longer had ideal tremor reduction with a standard system, replacing their deep brain stimulation with a directional system significantly improved their tremor and quality of life. Up-front implantation of directional deep brain stimulation leads may provide better tremor control in those patients who progress at a later time point.

Cerebral Small Vessel Disease, Risk Factors, and Cognition in Tenants of Precarious Housing.

BACKGROUND AND PURPOSE: We aim to describe the burden, characteristics, and cognitive associations of cerebral small vessel disease in a Canadian sample living with multimorbidity in precarious housing. METHODS: Participants received T1, T2-fluid-attenuated inversion recovery, and susceptibility-weighted imaging 3T magnetic resonance imaging sequences and comprehensive clinical, laboratory, and cognitive assessments. Cerebral small vessel disease burden was characterized using a modified Small Vessel Disease (mSVD) score. One point each was given for moderate-severe white matter hyperintensities, ≥1 cerebral microbleeds, and ≥1 lacune. Multivariable regression explored associations between mSVD score, risk factors, and cognitive performance. RESULTS: Median age of the 228 participants (77% male) was 44.7 years (range, 23.3-63.2). In n=188 participants with consistent good quality magnetic resonance imaging sequences, mSVD scores were 0 (n=127, 68%), 1 (n=50, 27%), and 2 (n=11, 6%). Overall, one-third had an mSVD ≥1 n=61 (32%); this proportion was unchanged when adding participants with missing sequences n=72/228 (32%). The most prevalent feature was white matter hyperintensities 53/218 (24%) then cerebral microbleed 16/191 (8%) and lacunes 16/228 (7%). Older age (odds ratio, 1.10 [95% CI, 1.05-1.15], P<0.001), higher diastolic blood pressure (odds ratio, 1.05 [95% CI, 1.01-1.09], P=0.008), and a history of injection drug use (odds ratio, 3.13 [95% CI, 1.07-9.16], P=0.037) had significant independent associations with a mSVD score of ≥1 in multivariable analysis. mSVD ≥1 was associated with lower performance on tests of verbal memory, sustained attention, and decision-making, contributing 4% to 5% of the variance in each cognitive domain. CONCLUSIONS: The 32% prevalence of cerebral small vessel disease in this young, socially marginalized cohort was higher than expected for age and was associated with poorer cognitive performance.