Vol 53, No 7 | Stroke

Abstract Export Citations PDF/EPUB
Cardiovascular events after primary intracerebral hemorrhage (ICH) have emerged as a leading cause of poor functional outcomes and mortality during the long-term recovery after an ICH. These events encompass arterial ischemic events such as ischemic stroke and myocardial infarction, arterial hemorrhagic events that include recurrent ICH, and venous thrombotic events such as venous thromboembolism. The purpose of this review is to summarize the cardiovascular complications after ICH, epidemiology and associated risk factors, and their impact on ICH outcomes. Additionally, we will highlight possible pathophysiological mechanisms to explain the short- and long-term increased risks of ischemic and hemorrhagic events after ICH. Finally, we will highlight potential secondary stroke and venous thrombotic prevention strategies often not considered after ICH, balanced against the risk of ICH recurrence.

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities

Michael T. Mullen

and

Craig S. Anderson

Stroke. 2022 | Volume 53, Issue 7: 2142–2151,

originally publishedJune 3, 2022,

https://doi.org/10.1161/STROKEAHA.121.036885

is accompanied by
- Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage
  - Kevin N. Sheth
  - Magdy Selim
  - Volume 53Issue 7Stroke
  - 27 June 2022
- Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation
  - Laurent Puy
  - Rachel Forman
  - Charlotte Cordonnier
  - Kevin N. Sheth
  - Volume 53Issue 7Stroke
  - 27 June 2022
- Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage
  - Ashkan Shoamanesh
  - Magdy Selim
  - Volume 53Issue 7Stroke
  - 6 June 2022
- Cardiovascular Events After Intracerebral Hemorrhage
  - Linxin Li
  - Santosh B. Murthy
  - Volume 53Issue 7Stroke
  - 8 June 2022

is companion of
- Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage
  - Kevin N. Sheth
  - Magdy Selim
  - Volume 53Issue 7Stroke
  - 27 June 2022
- Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation
  - Laurent Puy
  - Rachel Forman
  - Charlotte Cordonnier
  - Kevin N. Sheth
  - Volume 53Issue 7Stroke
  - 27 June 2022
- Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage
  - Ashkan Shoamanesh
  - Magdy Selim
  - Volume 53Issue 7Stroke
  - 6 June 2022
- Cardiovascular Events After Intracerebral Hemorrhage
  - Linxin Li
  - Santosh B. Murthy
  - Volume 53Issue 7Stroke
  - 8 June 2022

Abstract Export Citations PDF/EPUB
Blood pressure (BP) is the most important modifiable risk factor for intracerebral hemorrhage (ICH). Elevated BP is associated with an increased risk of ICH, worse outcome after ICH, and in survivors, higher risks of recurrent ICH, ischemic stroke, myocardial infarction, and cognitive impairment/dementia. As intensive BP control probably improves the chances of recovery from acute ICH, the early use of intravenous or oral medications to achieve a systolic BP goal of <140 mm Hg within the first few hours of presentation is reasonable for being applied in most patients. In the long-term, oral antihypertensive drugs should be titrated as soon as possible to achieve a goal BP <130/80 mm Hg and again in all ICH patients regardless of age, location, or presumed mechanism of ICH. The degree of sustained BP reduction, rather than the choice of BP-lowering agent(s), is the most important factor for optimizing risk reduction, with varying combinations of thiazide-type diuretics, long-acting calcium channel blockers, ACE (angiotensin-converting enzyme) inhibitors or angiotensin receptor blockers, being the mainstay of therapy. As most patients will require multiple BP-lowering agents, and physician inertia and poor adherence are major barriers to effective BP control, single-pill combination therapy should be considered as the choice of management where available. Increased population and clinician awareness, and innovations to solving patient, provider, and social factors, have much to offer for improving BP control after ICH and more broadly across high-risk groups. It is critical that all physicians, especially those managing ICH patients, emphasize the importance of BP control in their practice.

Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation

Laurent Puy

,

Rachel Forman

,

Charlotte Cordonnier

and

Kevin N. Sheth

Stroke. 2022 | Volume 53, Issue 7: 2152–2160,

originally publishedJune 27, 2022,

https://doi.org/10.1161/STROKEAHA.122.036888

is accompanied by
- Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage
  - Kevin N. Sheth
  - Magdy Selim
  - Volume 53Issue 7Stroke
  - 27 June 2022
- Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities
  - Michael T. Mullen
  - Craig S. Anderson
  - Volume 53Issue 7Stroke
  - 3 June 2022
- Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage
  - Ashkan Shoamanesh
  - Magdy Selim
  - Volume 53Issue 7Stroke
  - 6 June 2022
- Cardiovascular Events After Intracerebral Hemorrhage
  - Linxin Li
  - Santosh B. Murthy
  - Volume 53Issue 7Stroke
  - 8 June 2022

is companion of
- Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage
  - Kevin N. Sheth
  - Magdy Selim
  - Volume 53Issue 7Stroke
  - 27 June 2022
- Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities
  - Michael T. Mullen
  - Craig S. Anderson
  - Volume 53Issue 7Stroke
  - 3 June 2022
- Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage
  - Ashkan Shoamanesh
  - Magdy Selim
  - Volume 53Issue 7Stroke
  - 6 June 2022
- Cardiovascular Events After Intracerebral Hemorrhage
  - Linxin Li
  - Santosh B. Murthy
  - Volume 53Issue 7Stroke
  - 8 June 2022

Abstract Export Citations PDF/EPUB
Optimal antithrombotic management after intracerebral hemorrhage remains one of the central unresolved issues for patients who survive, especially for those patients with atrial fibrillation. Given the observational nature of the studies regarding anticoagulation resumption after intracerebral hemorrhage, there is uncertainty regarding resumption of oral anticoagulation therapy and its timing. There is limited high-quality evidence to guide clinical practice, leading to significant practice variation and uncertainty for patients and providers. Here, we aim to provide the key elements to guide clinicians in their individual decision: whether or not to start or resume anticoagulation in patients with a history of intracerebral hemorrhage.

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

Ashkan Shoamanesh

and

Magdy Selim

Stroke. 2022 | Volume 53, Issue 7: 2161–2170,

originally publishedJune 6, 2022,

https://doi.org/10.1161/STROKEAHA.122.036889

is accompanied by
- Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage
  - Kevin N. Sheth
  - Magdy Selim
  - Volume 53Issue 7Stroke
  - 27 June 2022
- Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities
  - Michael T. Mullen
  - Craig S. Anderson
  - Volume 53Issue 7Stroke
  - 3 June 2022
- Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation
  - Laurent Puy
  - Rachel Forman
  - Charlotte Cordonnier
  - Kevin N. Sheth
  - Volume 53Issue 7Stroke
  - 27 June 2022
- Cardiovascular Events After Intracerebral Hemorrhage
  - Linxin Li
  - Santosh B. Murthy
  - Volume 53Issue 7Stroke
  - 8 June 2022

is companion of
- Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage
  - Kevin N. Sheth
  - Magdy Selim
  - Volume 53Issue 7Stroke
  - 27 June 2022
- Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities
  - Michael T. Mullen
  - Craig S. Anderson
  - Volume 53Issue 7Stroke
  - 3 June 2022
- Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation
  - Laurent Puy
  - Rachel Forman
  - Charlotte Cordonnier
  - Kevin N. Sheth
  - Volume 53Issue 7Stroke
  - 27 June 2022
- Cardiovascular Events After Intracerebral Hemorrhage
  - Linxin Li
  - Santosh B. Murthy
  - Volume 53Issue 7Stroke
  - 8 June 2022

Abstract Export Citations PDF/EPUB
Hyperlipidemia is common in patients with intracerebral hemorrhage (ICH). Accumulating evidence indicates that patients with ICH are at risk for future hemorrhage recurrence, cardiovascular disease, and ischemic stroke and highlights the importance of secondary prevention of vascular events after ICH. Although the benefits of intensive treatment of hyperlipidemia for reducing ischemic cardiac and vascular events in patients with ischemic stroke are well established, the benefit versus harm in patients with ICH are less clear. Epidemiological studies suggest that hyperlipidemia is protective against ICH and that intensive lowering of lipids is associated with increased risk for ICH. Similarly, although currently available lipid-lowering treatments have been thoroughly studied in patients with ischemic cardiac and vascular disease, only few randomized trials of these therapies included a very small number of patients with history of ICH. Thus, limiting any definitive conclusions regarding the safety and net benefit of these treatments in ICH populations. Currently, there is no consensus regarding the optimal strategy for management of hyperlipidemia after ICH. In this article, we review relevant literature to outline the competing risks and benefits of lipid-lowering treatments in this vulnerable patient population. We suggest a treatment paradigm based on available data but note that data from dedicated randomized trials are needed to build the necessary evidence to guide optimal lipid-lowering strategy in patients with a history of ICH.

Priming Intermittent Theta Burst Stimulation for Hemiparetic Upper Limb After Stroke: A Randomized Controlled Trial

Jack Jiaqi Zhang

,

Zhongfei Bai

and

Kenneth N.K. Fong

Stroke. 2022 | Volume 53, Issue 7: 2171–2181,

originally publishedMarch 23, 2022,

https://doi.org/10.1161/STROKEAHA.121.037870

Abstract Export Citations PDF/EPUB

Background:
Intermittent theta burst stimulation (iTBS) creates a state with increased excitability that permits treatment modalities to induce neuroplasticity and motor learning. Continuous theta burst stimulation before iTBS may induce metaplasticity and boost the facilitatory effect of iTBS. This study investigated the effects of priming iTBS (ie, applying continuous theta burst stimulation before iTBS) on poststroke hemiparetic upper limb recovery.

Methods:
In this randomized controlled trial, 42 patients with chronic stroke were recruited and randomly allocated to 10 sessions of either priming iTBS, nonpriming iTBS, or sham stimulation to the ipsilesional motor cortex, immediately before robot-assisted training. Outcomes included Fugl-Meyer Assessment-Upper Extremity, Action Research Arm Test and mean movement velocity during each robot-assisted training session. Twenty-one patients were enrolled for measuring the sensorimotor beta event-related desynchronization induced by either mirror visual feedback or movement.

Results:
The Fugl-Meyer Assessment-Upper Extremity scores revealed a significant time-by-group interaction (P=0.011). Priming and nonpriming iTBS were both superior to sham stimulation in post hoc comparisons; however, the superiority was diminished at follow-up. Among patients with a higher functioning upper limb, priming iTBS yielded a significantly greater improvement in Fugl-Meyer Assessment-Upper Extremity scores than nonpriming iTBS (P=0.025) and sham stimulation (P=0.029) did. No significant interaction was found when analyzing the Action Research Arm Test and mean movement velocity. Priming iTBS enhanced the patients’ mirror visual feedback–induced high beta sensorimotor event-related desynchronization over their ipsilesional hemisphere.

Conclusions:
Priming and nonpriming iTBS are both superior to sham stimulation in enhancing treatment gains from robot-assisted training, and patients with a higher functioning upper limb may experience more benefits from priming iTBS. Priming iTBS may facilitate poststroke motor learning by enhancing the permissiveness of the ipsilesional sensorimotor area to therapeutic sensory modalities, such as the mirror visual feedback.

Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04034069. Graphical Abstract

Robot-Assisted Training as Self-Training for Upper-Limb Hemiplegia in Chronic Stroke: A Randomized Controlled Trial

Takashi Takebayashi

,

Kayoko Takahashi

,

Satoru Amano

,

Masahiko Gosho

,

Masahiro Sakai

,

Koichi Hashimoto

,

Kenji Hachisuka

,

Yuki Uchiyama

and

Kazuhisa Domen

Stroke. 2022 | Volume 53, Issue 7: 2182–2191,

originally publishedMarch 29, 2022,

https://doi.org/10.1161/STROKEAHA.121.037260

Abstract Export Citations PDF/EPUB

Background:
This study aimed to examine whether robotic self-training improved upper-extremity function versus conventional self-training in mild-to-moderate hemiplegic chronic stroke patients.

Methods:
Study design was a multi-center, prospective, randomized, parallel-group study comparing three therapist-guided interventions (1-hour sessions, 3×/wk, 10 weeks). We identified 161 prospective patients with chronic, poststroke, upper-limb hemiplegia treated at participating rehabilitation centers. Patients were enrolled between November 29, 2016, and November 12, 2018 in Japan. A blinded web-based allocation system was used to randomly assign 129 qualifying patients into 3 groups: (1) conventional self-training plus conventional therapy (control, N=42); (2) robotic self-training (ReoGo-J) plus conventional therapy (robotic therapy [RT], N=44); or (3) robotic self-training plus constraint-induced movement therapy (N=43). Primary outcome: Fugl-Meyer Assessment for upper-extremity. Secondary outcomes: Motor Activity Log-14 amount of use and quality of movement; Fugl-Meyer Assessment shoulder/elbow/forearm, wrist, finger, and coordination scores; Action Research Arm Test Score; Motricity Index; Modified Ashworth Scale; shoulder, elbow, forearm, wrist, and finger range of motion; and Stroke Impact Scale (the assessors were blinded). Safety outcomes were adverse events.

Results:
Safety was assessed in 127 patients. An intention-to-treat full analysis set (N=121), and a per-protocol set (N=115) of patients who attended 80% of sessions were assessed. One severe adverse event was recorded, unrelated to the robotic device. No significant differences in Fugl-Meyer Assessment for upper-extremity scores were observed between groups (RT versus control: −1.04 [95% CI, −2.79 to 0.71], P=0.40; RT versus movement therapy: −0.33 [95% CI, −2.02 to 1.36], P=0.90). The RT in the per-protocol set improved significantly in the Fugl-Meyer Assessment for upper-extremity shoulder/elbow/forearm score (RT versus control: −1.46 [95% CI, −2.63 to −0.29]; P=0.037).

Conclusions:
Robotic self-training did not improve upper-limb function versus usual self-training, but may be effective combined with conventional therapy in some populations (per-protocol set).

Registration:
URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000022509. Graphical Abstract

Tailored Sitting Tai Chi Program for Subacute Stroke Survivors: A Randomized Controlled Trial

Jie Zhao

,

Janita Pak Chun Chau

,

Aileen Wai Kiu Chan

,

Qiang Meng

,

Kai Chow Choi

,

Xiaoqi Xiang

,

Yali Zhao

,

Rong He

and

Qin Li

Stroke. 2022 | Volume 53, Issue 7: 2192–2203,

originally publishedApril 7, 2022,

https://doi.org/10.1161/STROKEAHA.121.036578

Abstract Export Citations PDF/EPUB

Background:
The initiation of exercise during rehabilitation at the subacute stage could provide stroke survivors with an approach to recovery that capitalizes on unique physiological conditions and promotes spontaneous recovery. We aimed to examine the effects of a tailored sitting Tai Chi program on recovery outcomes among subacute stroke survivors.

Methods:
We conducted a 12-week assessor-blind randomized controlled trial in China. Subacute stroke survivor-caregiver dyads were recruited and randomly assigned to either the sitting Tai Chi group (n=80) or attention control group (n=80). Outcomes including upper limb function (Fugl-Meyer Assessment Upper Extremity & Wolf Motor Function Test), balance control (Berg Balance Scale), sitting balance control (Trunk Impairment Scale), depressive symptoms (Geriatric Depression Scale Short Form), shoulder range of motion, shoulder pain (ShoulderQ), activities of daily living (Modified Barthel Index), and quality of life (Stroke Specific Quality of Life Scale) were measured at baseline, in-process, immediately post, and 4-week postintervention.

Results:
Immediately postintervention, the sitting Tai Chi group (n=69) showed significant upper limb function improvement in the primary outcomes including the performance time (regression coefficient of the group-by-time interaction, B=–21.415 [95% CI, –31.000 to –11.831]) and functional ability (B=10.146 [95% CI, 4.886–15.406]) domains of the Wolf Motor Function Test, balance control (B, 4.972 [95% CI, 1.356–8.588]), and sitting balance control (B=4.397 [95% CI, 2.699–6.096]). Compared with the control group (n=65), improvements were also observed in secondary outcomes including depressive symptoms (B=–1.626 [95% CI, –2.304 to –0.948]), shoulder extension (B=4.518 [95% CI, 0.893–8.144]), activities of daily living (B=5.510 [95% CI, 0.450–10.569]), and quality of life (B=15.680 [95% CI, 7.255–24.105]).

Conclusions:
The results support the effectiveness of a tailored sitting Tai Chi program in improving recovery outcomes among subacute stroke survivors and provide additional knowledge to support the clinical implementation of such a program.

Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04138407. Graphical Abstract

Effect of Deferoxamine on Trajectory of Recovery After Intracerebral Hemorrhage: A Post Hoc Analysis of the i-DEF Trial

Lydia Foster

,

Laura Robinson

,

Sharon D. Yeatts

,

Robin A. Conwit

,

Amjad Shehadah

,

Vasileios Lioutas

,

Magdy Selim

and

on behalf of the i-DEF Investigators

Stroke. 2022 | Volume 53, Issue 7: 2204–2210,

originally publishedMarch 21, 2022,

https://doi.org/10.1161/STROKEAHA.121.037298

Abstract Export Citations PDF/EPUB

Background:
There are limited data on the trajectory of recovery and long-term functional outcomes after intracerebral hemorrhage (ICH). Most ICH trials have conventionally assessed outcomes at 3 months following the footsteps of ischemic stroke. The i-DEF trial (Intracerebral Hemorrhage Deferoxamine Trial) assessed modified Rankin Scale (mRS) longitudinally at prespecified time points from day 7 through the end of the 6-month follow-up period. We evaluated the trajectory of mRS among trial participants and examined the effect of deferoxamine on this trajectory.

Methods:
We performed a post hoc analysis of the i-DEF trial, a multicenter, randomized, placebo-controlled, double-blind, futility-design, phase 2 clinical trial, based on the actual treatment received. Favorable outcome was defined as mRS score of 0–2. A generalized linear mixed model was used to evaluate the outcome trajectory over time, as well as whether the trajectory was altered by deferoxamine, after adjustments for randomization variables, presence of intraventricular hemorrhage, and ICH location.

Results:
A total of 291 subjects were included in analysis (145 placebo and 146 deferoxamine). The proportion of patients with mRS score of 0–2 continually increased from day 7 to 180 in both groups (interaction P<0.0001 for time in main effects model), but treatment with deferoxamine favorably altered the trajectory (interaction P=0.0010). Between day 90 and 180, the deferoxamine group improved (P=0.0001), whereas there was not significant improvement in the placebo arm (P=0.3005).

Conclusions:
A large proportion of patients continue to improve up to 6 months after ICH. Future ICH trials should assess outcomes past 90 days for a minimum of 6 months. In i-DEF, treatment with deferoxamine seemed to accelerate and alter the trajectory of recovery as assessed by mRS.

Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT02175225. Graphical Abstract

Clinical Results of the Advanced Neurovascular Access Catheter System Combined With a Stent Retriever in Acute Ischemic Stroke (SOLONDA)

Manuel Requena

,

Marc Ribo

,

Joaquin Zamarro

,

Pedro Vega

,

Jordi Blasco

,

Eva María González

,

María Del Mar Freijo

,

Jose Carlos Mendez Cendón

,

María Ángeles de Miquel

,

David Hernández

,

Manuel Moreu

,

Sebastià Remollo

,

Sonia Sánchez

,

David S. Liebeskind

,

Tommy Andersson

,

Christophe Cognard

,

Raul Nogueira

and

Alejandro Tomasello

Stroke. 2022 | Volume 53, Issue 7: 2211–2219,

originally publishedApril 1, 2022,

https://doi.org/10.1161/STROKEAHA.121.037577

Correction(s) for this article
- Correction to: Clinical Results of the Advanced Neurovascular Access Catheter System Combined With a Stent Retriever in Acute Ischemic Stroke (SOLONDA)
  - Volume 53Issue 7Stroke
  - 27 June 2022

Abstract Export Citations PDF/EPUB

Background:
The Advanced Neurovascular Access (ANA) thrombectomy system is a novel stroke thrombectomy device comprising a self-expanding funnel designed to reduce clot fragmentation by locally restricting flow while becoming as wide as the lodging artery. Once deployed, the ANA device allows distal aspiration combined with a stent retriever to mobilize the clot into the funnel where it remains copped during extraction. We investigated the safety and efficacy of ANA catheter system.

Methods:
SOLONDA (Solitaire in Combination With the ANA Catheter System as Manufactured by Anaconda) was a prospective, open, single-arm, multicenter trial with blinded assessment of the primary outcome by an independent core lab. Patients with anterior circulation vessel occlusion admitted within 8 hours from symptom onset were eligible. The primary end point was successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b–3) with ≤3 passes of the ANA device in combination with stent retriever, before the use of rescue therapy in the intention to treat population. Primary predefined analysis was noninferiority as compared to the performance end point observed in HERMES (High Effective Reperfusion Using Multiple Endovascular Devices).

Results:
After enrollment of 74 patients, an interim analysis was conducted, and the trial Steering Committee decided to terminate recruitment due to safety and performance objectives were reached. Mean age was 71.6 (SD 8.9) years, 46.6% women and median National Institutes of Health Stroke Scale on admission 14 (interquartile range, 10–19). Successful reperfusion within 3 passes before rescue therapy was achieved in 60/72 (83.3% [95% CI, 74.7%–91.9%]) with a rate of complete reperfusion (modified Thrombolysis in Cerebral Infarction score 2c–3) of 60% (95% CI, 48.4%–71.1%; 43/72 patients). After noninferiority was confirmed (P<0.01), the ANA device also showed superiority in the rate of successful reperfusion with ≤3 passes (P=0.02). First-pass successful recanalization rate was 55.6% (95% CI, 44.1%–67.0%), with a first-pass complete recanalization rate of 38.9% (95% CI, 27.6%–50.1%). Rescue therapy to obtain a modified Thrombolysis in Cerebral Infarction score 2b–3 was needed in 12/72 (17%) patients. At 90 days, the rate of favorable functional outcome (modified Rankin Scale score 0–2) was 57.5% (95% CI, 46.2%–68.9%), and the rate of excellent functional outcome (modified Rankin Scale score 0–1) was 45.2% (95% CI, 33.8%–56.6%). The rate of severe adverse device related was 1.4%.

Conclusions:
In this clinical experience, the ANA device achieved a high rate of complete recanalization with a preliminary good safety profile and favorable 90 days clinical outcomes.

Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04095767. Graphical Abstract

Functional Outcomes of Patients ≥85 Years With Acute Ischemic Stroke Following EVT: A HERMES Substudy

Rosalie V. McDonough

,

Johanna M. Ospel

,

Bruce C.V. Campbell

,

Michael D. Hill

,

Jeffrey L. Saver

,

Diederik W.J. Dippel

,

Andrew M. Demchuk

,

Charles B.L.M. Majoie

,

Scott B. Brown

,

Peter J. Mitchell

,

Serge Bracard

,

Francis Guillemin

,

Tudor G. Jovin

,

Keith W. Muir

,

Philip White

,

Mayank Goyal

and

on behalf of the HERMES Collaborators

Stroke. 2022 | Volume 53, Issue 7: 2220–2226,

originally publishedJune 15, 2022,

https://doi.org/10.1161/STROKEAHA.121.037770

Abstract Export Citations PDF/EPUB

Background:
Observational studies have shown endovascular treatment (EVT) for acute ischemic stroke to be effective in the elderly, despite resulting in poorer outcomes and higher rates of mortality compared with younger patients. Randomized data on the effect of advanced age on outcomes following EVT are, however, lacking. Our aim was to assess the EVT effect for ischemic stroke in patients aged ≥85 years and the influence of age on outcome in a large, randomized trial dataset.

Methods:
Data were from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration, a meta-analysis of 7 randomized trials published between January 1, 2010, and May 31, 2017, that tested the efficacy of EVT. A possible multiplicative interaction effect of age on the relationship between treatment and outcome was investigated. Ordinal logistic regression tested the association between EVT and 90-day functional outcome (modified Rankin Scale, primary outcome) in patients ≥85 years. Multivariable binary logistic regression was performed to compare primary and secondary outcomes (modified Rankin Scale score of 0–2/5–6) of patients ≥85 years versus those <85 years.

Results:
We included 1764 patients in the analysis, of whom 77 (4.4%) were ≥85 years old. A significant interaction of age and treatment on poor outcome (modified Rankin Scale score of 5–6, P=0.020) and mortality (P=0.031) was observed, with older adults having worse functional outcomes at 90 days compared with younger patients (adjusted common odds ratio, 0.20 [95% CI, 0.13–0.33]). However, a benefit of EVT was observed in the ≥85-year-old patient subgroup (common odds ratio, 4.20 [95% CI, 1.56–11.32]). Age ≥85 years was not significantly associated with differing rates of symptomatic intracerebral hemorrhage or reperfusion (adjusted odds ratio, 1.92 [95% CI, 0.71–5.15] and adjusted odds ratio, 0.91 [95% CI, 0.40–2.06], respectively).

Conclusions:
Patients ≥85 years old with independent premorbid function more often achieve good functional outcomes and have lower rates of mortality when treated with EVT compared with conservative management, with an observed treatment effect modification of age on outcome. EVT should therefore not be withheld in this subgroup. Graphical Abstract

Is Endovascular Thrombectomy for the Very Elderly?

Claire J. Creutzfeldt

,

Michael R. Levitt

and

Thabele M. Leslie-Mazwi

Stroke. 2022 | Volume 53, Issue 7: 2227–2229,

originally publishedJune 15, 2022,

https://doi.org/10.1161/STROKEAHA.122.039340

Impact of Shunting Practice Patterns During Carotid Endarterectomy for Symptomatic Carotid Stenosis

Francesco Squizzato

,

Jeffrey J. Siracuse

,

Fahad Shuja

,

Jill Colglazier

,

Parvathi Balachandran Wilkins

,

Philip P. Goodney

,

Benjamin Sands Brooke

and

Randall R. DeMartino

Stroke. 2022 | Volume 53, Issue 7: 2230–2240,

originally publishedMarch 24, 2022,

https://doi.org/10.1161/STROKEAHA.121.037657

Abstract Export Citations PDF/EPUB

Background:
We aimed to assess the effect of surgeons’ shunting practice and shunt use on the early outcomes of carotid endarterectomy (CEA) in recently symptomatic patients.

Methods:
We conducted a retrospective observational study based on a multicenter national prospective database. The Vascular Quality Initiative database (2010–2019) was queried for CEAs performed within 14 days after an ipsilateral stroke or transient ischemic attack. Surgeons were gauged as routine shunters if they shunted in >95% of CEAs, otherwise were classified as selective shunters. In-hospital stroke and death rates were compared between routine and selective shunters, stratifying by type of index event (transient ischemic attack versus stroke) and timing of CEA (≤2 versus >2 days).

Results:
Thirteen thousand four hundred sixty-nine CEAs were performed after a transient ischemic attack (43%) or stroke (57%), 3186 (24%) by routine shunters, and 10 283 (76%) by selective shunters. Comparing routine and selective shunters, in-hospital stroke (1.9% versus 2.4%; P=0.09) and death (0.4% versus 0.5%; P=0.73) rates were similar. A lower stroke rate (1.5% versus 4.2%; P=0.02) was achieved by routine shunters for CEA performed <2 days after an ischemic stroke. Among selective shunters, a higher stroke rate occurred in case of shunt use (2.9% versus 2.3%; P<0.01), mainly due to cases presenting with stroke (3.5% versus 2.4%; P<0.01) but not transient ischemic attack (1.8% versus 1.5%; P=0.57). Awake anesthesia was adopted in 7.8% of cases by selective shunters and in 0.8% by routine shunters, without impact on the perioperative stroke rate (1.8% versus 2.3%; P=0.349).

Conclusions:
In this large national cohort, the overall outcomes of CEA were similar between routine and selective shunters. A lower postoperative stroke rate was achieved by routine shunters in CEA performed <2 days after an ischemic stroke. Among selective shunters, intraoperatively indicated shunting determined an increased stroke rate, likely due to intraoperative hypoperfusion. These data may guide the decision regarding timing of CEA and shunting intention in symptomatic patients. Graphical Abstract

Cerebral Venous Sinus Thrombosis in Preterm Infants

Rhandi Christensen

,

Pradeep Krishnan

,

Gabrielle deVeber

,

Nomazulu Dlamini

,

Daune MacGregor

,

Elizabeth Pulcine

and

Mahendranath Moharir

Stroke. 2022 | Volume 53, Issue 7: 2241–2248,

originally publishedApril 18, 2022,

https://doi.org/10.1161/STROKEAHA.121.037621

Abstract Export Citations PDF/EPUB

Background:
Neonatal cerebral venous sinus thrombosis (CVST) can lead to brain injury and neurodevelopmental impairments. Previous studies of neonatal CVST have focused on term infants, and studies of preterm infants are lacking. In this study, we examined the clinical and radiological features, treatment and outcome of CVST in preterm infants.

Methods:
This was a retrospective, consecutive cohort study of preterm infants (gestational age <37 weeks) with radiologically confirmed CVST. All magnetic resonance imaging/MRV and CT/CTV scans were re-reviewed to study thrombus characteristics and pattern of brain injury. Outcome was assessed by the validated pediatric stroke outcome measure at the most recent clinic visit.

Results:
Twenty-six preterm infants with CVST were studied. Of these, 65% were moderate-late preterm (32–37 weeks), 27% very preterm (28–32 weeks), and 8% extreme preterm (<28 weeks). Most (73%) were symptomatic at presentation with seizures or abnormal exam. Transverse (85%) and superior sagittal (42%) sinuses were common sites of thrombosis. Parenchymal brain injury was predominantly periventricular (35%) and deep white matter (31%) in location. Intraventricular hemorrhage occurred in 46%. Most infants (69%) were treated with anticoagulation. No treated infant (including eleven with pretreatment hemorrhage) had new or worsening post-treatment hemorrhage. Outcomes ranged from no deficits (50%), mild-moderate (25%), and severe (25%) impairment.

Conclusions:
In our sample of preterm infants with CVST, more than one-quarter were asymptomatic. White matter brain lesions predominated and one-half had neurological deficits at follow-up. Anticoagulation of preterm CVST in this small cohort appeared to be safe. Larger studies of preterm CVST are needed. Graphical Abstract

Impact of Age on Systemic Inflammatory Profile of Patients With ST-Segment–Elevation Myocardial Infarction and Acute Ischemic Stroke

Thomas Bochaton

,

Simon Leboube

,

Alexandre Paccalet

,

Claire Crola Da Silva

,

Marielle Buisson

,

Nathan Mewton

,

Camille Amaz

,

Yvonne Varillon

,

Eric Bonnefoy-Cudraz

,

Gilles Rioufol

,

Tae-Hee Cho

,

Michel Ovize

,

Gabriel Bidaux

,

Norbert Nighoghossian

and

Laura Mechtouff

Stroke. 2022 | Volume 53, Issue 7: 2249–2259,

originally publishedMarch 31, 2022,

https://doi.org/10.1161/STROKEAHA.121.036806

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Background:
Aging is associated with a chronic low-grade inflammatory state. This condition may affect the acute inflammatory response involved in ST-segment–elevation myocardial infarction (STEMI) or acute ischemic stroke (AIS). We sought to compare the profile of a set of circulating inflammatory markers between young and older patients admitted for STEMI or AIS.

Methods:
HIBISCUS-STEMI (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in ST Elevation Myocardial Infarction) and HIBISCUS-STROKE (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke) are 2 cohort studies that enrolled patients with STEMI treated with primary percutaneous coronary intervention in the cardiac intensive care unit of Lyon and patients with AIS treated with mechanical thrombectomy in the Lyon Stroke Center, respectively from 2016 to 2019. Patients were classified as older if they were ≥65 years and as young if they were <65 years. In both cohorts, CRP (C-reactive protein), IL (interleukin)-6, IL-8, IL-10, MCP (monocyte chemoattractant protein), sTNF-RI (soluble tumor necrosis factor receptor I), sST2 (soluble form suppression of tumorigenicity 2), and VCAM-1 (vascular cellular adhesion molecule-1) were measured on serum collected at 5 time points using enzyme-linked immunosorbent assay. A multiple logistic regression model was performed to detect an association between area under the curve of circulating inflammatory markers within the first 48 hours and older age.

Results:
A total of 260 patients with STEMI and 164 patients with AIS were included. Of them, there were 76 (29%) and 105 (64%) older patients with STEMI and AIS, respectively. Following multivariable analysis, a high area under the curve of IL-6 and sTNF-RI, a low lymphocyte count, and a high neutrophil-lymphocyte ratio at 24 hours were associated with older age in patients with STEMI and AIS.

Conclusions:
Older patients had higher IL-6 and sTFN-RI levels within the first 48 hours associated with a lower lymphocyte count and a higher neutrophil-lymphocyte ratio at 24 hours in both cohorts. Graphical Abstract

Age Alters Prevalence of Left Atrial Enlargement and Nonstenotic Carotid Plaque in Embolic Stroke of Undetermined Source

Solomon Oak

,

Brett L. Cucchiara

,

Lauren Thau

,

Thanh N. Nguyen

,

Anvitha Sathya

,

Sahily Reyes-Esteves

,

Nicholas Vigilante

,

Scott Kamen

,

Jillian Hall

,

Parth Patel

,

Rahul Garg

,

Mohamad Abdalkader

,

Jesse M. Thon

and

James E. Siegler

Stroke. 2022 | Volume 53, Issue 7: 2260–2267,

originally publishedMarch 31, 2022,

https://doi.org/10.1161/STROKEAHA.121.037522

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Background:
Nonstenotic carotid plaque and undetected atrial fibrillation are potential mechanisms of embolic stroke of undetermined source (ESUS), but it is unclear which is more likely to be the contributing stroke mechanism. We explored the relationship between left atrial enlargement (LAE) and nonstenotic carotid plaque across age ranges in an ESUS population.

Methods:
A retrospective multicenter cohort of consecutive patients with unilateral, anterior circulation ESUS was queried (2015 to 2021). LAE and plaque thickness were determined by transthoracic echocardiography and computed tomography angiography, respectively. Descriptive statistics were used to compare plaque features in relation to age and left atrial dimensions.

Results:
Among the 4155 patients screened, 273 (7%) met the inclusion criteria. The median age was 65 years (interquartile range [IQR] 54–74), 133 (48.7%) were female, and the median left atrial diameter was 3.5 cm (IQR 3.1–4.1). Patients with any LAE more frequently had hypertension (85.9% versus 67.2%, P<0.01), diabetes (41.0% versus 25.6%, P=0.01), dyslipidemia (56.4% versus 40.0%, P=0.01), and coronary artery disease (22.8% versus 11.3%, P=0.02). Carotid plaque thickness was greater ipsilateral versus contralateral to the stroke hemisphere in the overall cohort (median 1.9 mm [IQR 0–3] versus 1.5 mm [IQR 0–2.6], P<0.01); however, this was largely driven by the subgroup of patients without any LAE (median 1.8 mm [IQR 0–2.9] versus 1.5 mm [IQR 0–2.5], P<0.01). Compared with patients ≥70 years, younger patients had more carotid plaque ipsilateral versus contralateral (mean difference 0.42 mm±1.24 versus 0.08 mm±1.54, P=0.047) and less moderate-to-severe LAE (6.3% versus 15.3%, P=0.02).

Conclusions:
Younger patients with ESUS had greater prevalence of ipsilateral nonstenotic plaque, while the elderly had more LAE. The differential effect of age on the probability of specific mechanisms underlying ESUS should be considered in future studies. Graphical Abstract

Sex Differences in Short-Term and Long-Term Outcomes Among Patients With Acute Ischemic Stroke in China

Meng Wang

,

Chun-Juan Wang

,

Hong-Qiu Gu

,

Xia Meng

,

Yong Jiang

,

Xin Yang

,

Jing Zhang

,

Yun-Yun Xiong

,

Xing-Quan Zhao

,

Li-Ping Liu

,

Yi-Long Wang

,

Yong-Jun Wang

and

Zi-Xiao Li

Stroke. 2022 | Volume 53, Issue 7: 2268–2275,

originally publishedFebruary 8, 2022,

https://doi.org/10.1161/STROKEAHA.121.037121

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Background:
Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study.

Methods:
Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included. The primary outcomes were stroke recurrence, mortality, and unfavorable functional outcome (modified Rankin Scale > 2) at 3, 6, and 12 months. Cox regression model was used for stroke recurrence and mortality and logistic regression was used for the unfavorable functional outcome, and adjusted as follows: (1) Model 1: without adjustment; (2) Model 2: adjusted for potential risk factors, National Institutes of Health Stroke Scale at admission, prestroke modified Rankin Scale, tPA (tissue-type plasminogen activator) treatment, TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, and onset-to-door time; (3) Model 3: adjusted for covariates from model 2 in addition to blood pressure and blood serum covariates. Multiple imputation was used for missing values, and sensitivity analyses were conducted to describe sex differences by age groups.

Results:
One-third (2802/9038) of the patients were women. Women were significantly older than men (64.78±10.84 versus 61.26±11.42, P<0.001). In the fully adjusted model, female patients were more likely to have unfavorable functional outcomes at 3 months (odds ratio, 1.28 [1.09–1.50]), especially among patients aged 65 years or older (odds ratio, 1.39 [1.14–1.70]), but no difference was discovered in patients aged <65 years. There were no sex differences in stroke recurrence and mortality at 3, 6, or 12 months or unfavorable functional outcomes at 6 or 12 months after adjustment.

Conclusions:
Compared with men, women with AIS were less likely to have favorable outcomes at 3 months in China, especially among those over 65 years of age. Experts should aim to tailor secondary prevention strategies for high-risk patients. Graphical Abstract

Circulating Extracellular Vesicles in Stroke Patients Treated With Mesenchymal Stem Cells: A Biomarker Analysis of a Randomized Trial

Oh Young Bang

,

Eun Hee Kim

,

Yeon Hee Cho

,

Mi Jeong Oh

,

Jong-Won Chung

,

Won Hyuk Chang

,

Yun-Hee Kim

,

Seong Wook Yang

and

Michael Chopp

Stroke. 2022 | Volume 53, Issue 7: 2276–2286,

originally publishedMarch 28, 2022,

https://doi.org/10.1161/STROKEAHA.121.036545

Abstract Export Citations PDF/EPUB

Background:
Mesenchymal stem cells (MSCs) secrete trophic factors and extracellular vesicles (EVs). However, the level and role of EVs after MSC therapy in patients with stroke are unknown. We investigated whether circulating EVs and trophic factors are increased after MSCs and are related to the therapeutic benefits in the STARTING-2 trial (Stem Cell Application Researches and Trials in Neurology-2) participants.

Methods:
In this prospective randomized controlled trial, patients with chronic major stroke were assigned, in a 2:1 ratio, to receive autologous MSC intravenous injection (MSC group, n=39) or standard treatment (control group, n=15) and followed for 3 months. Detailed clinical assessment and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging were evaluated. Serial samples were collected, before/after MSCs therapy. The primary outcome measure was circulating factors that are associated with the clinical improvement in the Fugl-Meyer Assessment (secondary end point of the trial) and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging. Additional outcome measures were microRNAs and trophic factors enriched in the plasma EVs, obtained using quantitative polymerase chain reaction and ELISA, respectively.

Results:
Circulating EV levels were increased ≈5-fold (mean±SD, from 2.7×10⁹±2.2×10⁹ to 1.3×10¹⁰±1.7×10¹⁰ EVs/mL) within 24 hours after injection of MSCs (P=0.001). After adjustment of age, sex, baseline stroke severity, and the time interval from stroke onset to treatment, only the EV number was independently associated with improvement in motor function (odds ratio, 5.718 for EV number^Log [95% CI, 1.144–28.589]; P=0.034). Diffusion tensor image and resting-state functional magnetic resonance imaging showed that integrity of the ipsilesional corticospinal tract and intrahemispheric motor network were significantly correlated with circulating EV levels, respectively (P<0.05). MicroRNAs related to neurogenesis/neuroplasticity (eg, microRNA-18a-5p) were significantly increased in circulating EVs after MSC therapy (P=0.0479). In contrast, trophic factor levels were not changed after MSC therapy.

Conclusions:
This trial is the first to show that treatment of ischemic stroke patients with MSCs significantly increases circulating EVs, which were significantly correlated with improvement in motor function and magnetic resonance imaging indices of plasticity.

Registration:
URL: https://www.clinical trials.gov; Unique identifier: NCT01716481. Graphical Abstract

Stroke and Risk of Mental Disorders Compared With Matched General Population and Myocardial Infarction Comparators

Nils Skajaa

,

Kasper Adelborg

,

Erzsébet Horváth-Puhó

,

Kenneth J. Rothman

,

Victor W. Henderson

,

Lau Caspar Thygesen

and

Henrik Toft Sørensen

Stroke. 2022 | Volume 53, Issue 7: 2287–2298,

originally publishedMarch 23, 2022,

https://doi.org/10.1161/STROKEAHA.121.037740

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Background:
Accurate estimates of risks of poststroke outcomes from large population–based studies can provide a basis for public health policy decisions. We examined the absolute and relative risks of a spectrum of incident mental disorders following ischemic stroke and intracerebral hemorrhage.

Methods:
During 2004 to 2018, we used Danish registries to identify patients (≥18 years and with no hospital history of mental disorders), with a first-time ischemic stroke (n=76 767) or intracerebral hemorrhage (n=9344), as well as age-,sex-, and calendar year–matched general population (n=464 840) and myocardial infarction (n=92 968) comparators. We computed risk differences, considering death a competing event, and hazard ratios adjusted for income, occupation, education, and history of cardiovascular and noncardiovascular comorbidity.

Results:
Compared with the general population, following ischemic stroke, the 1-year risk difference was 7.3% (95% CI, 7.0–7.5) for mood disorders (driven by depression), 1.4% (95% CI, 1.3–1.5) for organic brain disorders (driven by dementia and delirium), 0.8% (95% CI, 0.7–0.8) for substance abuse disorders (driven by alcohol and tobacco abuse), and 0.5% (95% CI, 0.4–0.5) for neurotic disorders (driven by anxiety and stress disorders). For suicide, risk differences were near null. Hazard ratios were particularly elevated in the first year of follow-up, ranging from a 2- to a 4-fold increased hazard, decreasing thereafter. Compared with myocardial infarction patients, the 1-year risk difference was 4.9% (95% CI, 4.6 to 5.3) for mood disorders, 1.0% (95% CI, 0.8 to 1.1) for organic brain disorders, 0.1% (95% CI, 0.0 to 0.2) for substance abuse disorders, but −0.2% (95% CI, −0.2 to −0.1) for neurotic disorders. Hazard ratios during the first year of follow-up were elevated 1.1- to 1.8-fold for mood, organic brain, and neurotic disorders, while decreased 0.8-fold for neurotic disorders.

Conclusions:
The considerably greater risks of mental disorders following a stroke, particularly mood disorders, underline the importance of mental health evaluation after stroke. Graphical Abstract

Prediction of Recurrent Ischemic Stroke Using Registry Data and Machine Learning Methods: The Erlangen Stroke Registry

Asmir Vodencarevic

,

Michael Weingärtner

,

J. Jaime Caro

,

Dubravka Ukalovic

,

Marcus Zimmermann-Rittereiser

,

Stefan Schwab

and

Peter Kolominsky-Rabas

Stroke. 2022 | Volume 53, Issue 7: 2299–2306,

originally publishedApril 1, 2022,

https://doi.org/10.1161/STROKEAHA.121.036557

Abstract Export Citations PDF/EPUB

Background:
There have been multiple efforts toward individual prediction of recurrent strokes based on structured clinical and imaging data using machine learning algorithms. Some of these efforts resulted in relatively accurate prediction models. However, acquiring clinical and imaging data is typically possible at provider sites only and is associated with additional costs. Therefore, we developed recurrent stroke prediction models based solely on data easily obtained from the patient at home.

Methods:
Data from 384 patients with ischemic stroke were obtained from the Erlangen Stroke Registry. Patients were followed at 3 and 12 months after first stroke and then annually, for about 2 years on average. Multiple machine learning algorithms were applied to train predictive models for estimating individual risk of recurrent stroke within 1 year. Double nested cross-validation was utilized for conservative performance estimation and models’ learning capabilities were assessed by learning curves. Predicted probabilities were calibrated, and relative variable importance was assessed using explainable artificial intelligence techniques.

Results:
The best model achieved the area under the curve of 0.70 (95% CI, 0.64–0.76) and relatively good probability calibration. The most predictive factors included patient’s family and housing circumstances, rehabilitative measures, age, high calorie diet, systolic and diastolic blood pressures, percutaneous endoscopic gastrotomy, number of family doctor’s home visits, and patient’s mental state.

Conclusions:
Developing fairly accurate models for individual risk prediction of recurrent ischemic stroke within 1 year solely based on registry data is feasible. Such models could be applied in a home setting to provide an initial risk assessment and identify high-risk patients early. Graphical Abstract

Socioeconomic Inequalities in Reperfusion Therapy for Acute Ischemic Stroke

Sine Mette Øgendahl Buus

,

Marie Louise Schmitz

,

Pia Cordsen

,

Søren Paaske Johnsen

,

Grethe Andersen

and

Claus Ziegler Simonsen

Stroke. 2022 | Volume 53, Issue 7: 2307–2316,

originally publishedMay 17, 2022,

https://doi.org/10.1161/STROKEAHA.121.037687

This article is commented on by the following:
- Different Strokes for Different Folks: Socioeconomic Disadvantage and Access to Stroke Reperfusion Therapies
  - M. Carter Denny
  - Melina Gattellari
  - Volume 53Issue 7Stroke
  - 17 May 2022

Abstract Export Citations PDF/EPUB

Background:
Reperfusion therapies (thrombolysis and thrombectomy) are of paramount importance for the recovery after ischemic stroke. We aimed to investigate if socioeconomic status (SES) was associated with the chance of receiving reperfusion therapy for ischemic stroke in a country with tax-funded health care.

Methods:
This nationwide register-based cohort study included patients with ischemic stroke registered in the Danish Stroke Registry between 2015 and 2018. SES was determined by prestroke educational attainment, income level, and employment status. Data on SES was obtained from Statistics Denmark and linked on an individual level with data from the Danish Stroke Registry. Risk ratios (RR) for receiving reperfusion therapies were calculated using univariate and multivariable Poisson regression with robust variance.

Results:
A total of 37 187 ischemic stroke patients were included. Low SES, as defined by education, income and employment status, was associated with lower treatment rates. The socioeconomic gradient was most pronounced according to employment status, with intravenous thrombolysis rates of 23.7% versus 15.8%, and thrombectomy rates of 5.1% versus 2.8% for employed versus unemployed patients. When the analyses were restricted to patients with timely hospital arrival, and adjusted for age, sex and immigrant status, low SES according to income and employment remained unfavorable for the likelihood of receiving intravenous thrombolysis: adjusted RR, 0.90 (95% CI, 0.86–0.95) for low versus high income, and adjusted RR, 0.77 (95% CI, 0.71–0.84) for unemployed versus employed patients. Similarly, low SES according to income and employment status remained unfavorable for the likelihood of receiving thrombectomy: adjusted RR, 0.83 (95% CI, 0.72–0.95) for low versus high income and adjusted RR, 0.68 (95% CI, 0.53–0.88) for unemployed versus employed patients.

Conclusions:
Socioeconomic inequalities in reperfusion treatment rates among ischemic stroke patients prevail, even in a country with tax-funded universal health care. Graphical Abstract

Different Strokes for Different Folks: Socioeconomic Disadvantage and Access to Stroke Reperfusion Therapies

M. Carter Denny

and

Melina Gattellari

Stroke. 2022 | Volume 53, Issue 7: 2317–2319,

originally publishedMay 17, 2022,

https://doi.org/10.1161/STROKEAHA.122.039353

This article comments on the following:
- Socioeconomic Inequalities in Reperfusion Therapy for Acute Ischemic Stroke
  - Volume 53Issue 7Stroke
  - 17 May 2022

Biological Age Acceleration Is Lower in Women With Ischemic Stroke Compared to Men

Stroke. 2022 | Volume 53, Issue 7: 2320–2330,

originally publishedFebruary 25, 2022,

https://doi.org/10.1161/STROKEAHA.121.037419

Abstract Export Citations PDF/EPUB

Background:
Stroke onset in women occurs later in life compared with men. The underlying mechanisms of these differences have not been established. Epigenetic clocks, based on DNA methylation (DNAm) profiles, are the most accurate biological age estimate. Epigenetic age acceleration (EAA) measures indicate whether an individual is biologically younger or older than expected. Our aim was to analyze whether sexual dichotomy at age of stroke onset is conditioned by EAA.

Methods:
We used 2 DNAm datasets from whole blood samples of case-control genetic studies of ischemic stroke (IS), a discovery cohort of 374 IS patients (N women=163, N men=211), from GRECOS (Genotyping Recurrence Risk of Stroke) and SEDMAN (Dabigatran Study in the Early Phase of Stroke, New Neuroimaging Markers and Biomarkers) studies and a replication cohort of 981 IS patients (N women=411, N men=570) from BASICMAR register. We compared chronological age, 2 DNAm-based biomarkers of aging and intrinsic and extrinsic epigenetic age acceleration EAA (IEAA and extrinsic EAA, respectively), in IS as well as in individual IS etiologic subtypes. Horvath and Hannum epigenetic clocks were used to assess the aging rate. A proteomic study using the SOMAScan multiplex assay was performed on 26 samples analyzing 1305 proteins.

Results:
Women present lower Hannum-extrinsic EAA values, whereas men have higher Hannum-extrinsic EAA values (women=−0.64, men=1.24, P=1.34×10^-2); the same tendency was observed in the second cohort (women=−0.57, men=0.79, P=0.02). These differences seemed to be specific to cardioembolic and undetermined stroke subtypes. Additionally, 42 blood protein levels were associated with Hannum-extrinsic EAA (P<0.05), belonging to the immune effector process (P=1.54×10^-6) and platelet degranulation (P<8.74×10^-6) pathways.

Conclusions:
This study shows that sex-specific underlying biological mechanisms associated with stroke onset could be due to differences in biological age acceleration between men and women. Graphical Abstract

A Family and a Genome-Wide Polygenic Risk Score Are Independently Associated With Stroke in a Population-Based Study

Michelle Hämmerle

,

Lukas Forer

,

Sebastian Schönherr

,

Annette Peters

,

Harald Grallert

,

Florian Kronenberg

,

Christian Gieger

and

Claudia Lamina

Stroke. 2022 | Volume 53, Issue 7: 2331–2339,

originally publishedApril 7, 2022,

https://doi.org/10.1161/STROKEAHA.121.036551

Abstract Export Citations PDF/EPUB

Background:
Positive family history and genetic risk scores have been shown to independently capture those individuals with high risk for stroke. The aim of our study was to evaluate the amount of shared information between family history and genetic risk and to investigate their combined effect on the association with prevalent and incident stroke cases.

Methods:
We obtained a family risk score (FamRS), weighted for disease onset and family size as well as genome-wide polygenic risk score (PGS) including over 3.2 million single-nucleotide polymorphisms in the population-based prospective KORA F3 (Cooperative Health Research in the Region of Augsburg) study (n=3071) from Southern Germany. FamRS and PGS were evaluated separately and combined. The measures were once treated as continuous variables but also divided in the highest 20%, 10%, 5%, and 1% percentiles. Odds ratios via logistic regression and hazard ratios via Cox regression were estimated. A stroke event was defined as a hospitalization for stroke that was self-reported in a standardized interview by certified and supervised personnel.

Results:
The FamRS outperformed other simplified family measures such as affected parents or number of affected family members. FamRS and PGS were not correlated, and no individuals were observed with both very high FamRS and very high PGS (top 1% percentile). In a combined model, both FamRS and PGS were independently from each other associated with risk of stroke, also independent of other traditional risk factors (p [FamRS]=0.02, p [PGS]=0.005). Individuals in the top 1% of either FamRS or PGS were found to have >5-fold risk for stroke (odds ratios, 5.82 [95% CI, 2.08–14]; P=0.0002). The results for incident stroke events showed the same trend but were not significant.

Conclusions:
Our study shows that a family risk score and PGS capture different information concerning individual stroke risk. Combining the risk measures FamRS and PGS increases predictive power, as demonstrated in a population-based study. Graphical Abstract

Risk of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage

Andrew J. Durnford

,

Danyal Akarca

,

David Culliford

,

John Millar

,

Ridhima Guniganti

,

Enrico Giordan

,

Waleed Brinjikji

,

Ching-Jen Chen

,

Isaac Josh Abecassis

,

Michael Levitt

,

Adam J. Polifka

,

Colin P. Derdeyn

,

Edgar A. Samaniego

,

Amanda Kwasnicki

,

Ali Alaraj

,

Adriaan R.E. Potgieser

,

Stephanie Chen

,

Yoshiteru Tada

,

Ryan Phelps

,

Adib Abla

,

Junichiro Satomi

,

Robert M. Starke

,

J. Marc C. van Dijk

,

Sepideh Amin-Hanjani

,

Minako Hayakawa

,

Bradley Gross

,

W. Christopher Fox

,

Louis Kim

,

Jason Sheehan

,

Giuseppe Lanzino

,

Akash P. Kansagra

,

Rose Du

,

Rosalind Lai

,

Gregory J. Zipfel

,

Diederik O. Bulters

,

Jay F. Piccirillo

,

Hari Raman

,

Kim Lipsey;

,

Roanna Vine

,

Harry J. Cloft

,

David F. Kallmes

,

Bruce E. Pollock

,

Michael J. Link

,

Mohana Rao Patibandla

,

Dale Ding

,

Thomas Buell

,

Gabriella Paisan

,

R. Michael Meyer

,

Cory Kelly;

,

Jonathan Duffill

,

Adam Ditchfield

,

Jason Macdonald

,

Dimitri Laurent

,

Brian Hoh

,

Jessica Smith

,

Ashley Lockerman

,

L. Dade Lunsford

,

Brian T. Jankowitz

,

Santiago Ortega Gutierrez

,

David Hasan

,

Jorge A. Roa

,

James Rossen

,

Waldo Guerrero

,

Allen McGruder

,

Fady T. Charbel

,

Victor A. Aletich

,

Linda Rose-Finnell

,

Eric C. Peterson

,

Dileep R. Yavagal

,

Samir Sur

,

Yasuhisa Kanematsu

,

Nobuaki Yamamoto

,

Tomoya Kinouchi

,

Masaaki Korai

,

Izumi Yamaguchi

,

Yuki Yamamoto

,

Ethan Winkler

,

Michael Lawton

,

Martin Rutkowski

,

M. Ali Aziz Sultan

,

Nirav Patel

and

Kai U. Frerichs

Stroke. 2022 | Volume 53, Issue 7: 2340–2345,

originally publishedApril 14, 2022,

https://doi.org/10.1161/STROKEAHA.121.036450

Abstract Export Citations PDF/EPUB

Background:
Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage.

Methods:
Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference.

Results:
Of 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2–14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3–5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7–12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4–37.7; P, 0.026).

Conclusions:
The risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe. Graphical Abstract

Herniation World Federation of Neurosurgical Societies Scale Improves Prediction of Outcome in Patients With Poor-Grade Aneurysmal Subarachnoid Hemorrhage

Stroke. 2022 | Volume 53, Issue 7: 2346–2351,

originally publishedMarch 23, 2022,

https://doi.org/10.1161/STROKEAHA.121.036699

Abstract Export Citations PDF/EPUB

Background:
Favorable outcomes are seen in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage. Therefore, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. We previously modified the WFNS scale by requiring positive signs of brain stem dysfunction to assign grade V. This study aimed to validate the new herniation WFNS grading system in an independent prospective cohort.

Methods:
We conducted an international prospective multicentre study in poor-grade aneurysmal subarachnoid hemorrhage patients comparing the WFNS classification with a modified version—the herniation WFNS scale (hWFNS). Here, only patients who showed positive signs of brain stem dysfunction (posturing, anisocoric, or bilateral dilated pupils) were assigned hWFNS grade V. Outcome was assessed by modified Rankin Scale score 6 months after hemorrhage. The primary end point was the difference in specificity of the WFNS and hWFNS grading with respect to poor outcomes (modified Rankin Scale score 4–6).

Results:
Of the 250 patients included, 237 reached the primary end point. Comparing the WFNS and hWFNS scale after neurological resuscitation, the specificity to predict poor outcome increased from 0.19 (WFNS) to 0.93 (hWFNS) (McNemar, P<0.001) whereas the sensitivity decreased from 0.88 to 0.37 (P<0.001), and the positive predictive value from 61.9 to 88.3 (weighted generalized score statistic, P<0.001). For mortality, the specificity increased from 0.19 to 0.93 (McNemar, P<0.001), and the positive predictive value from 52.5 to 86.7 (weighted generalized score statistic, P<0.001).

Conclusions:
The identification of objective positive signs of brain stem dysfunction significantly improves the specificity and positive predictive value with respect to poor outcome in grade V patients. Therefore, a simple modification—presence of brain stem signs is required for grade V—should be added to the WFNS classification.

Registration:
URL: https://clinicaltrials.gov; Unique identifier: NCT02304328. Graphical Abstract

Hemorrhage Enlargement Is More Frequent in the First 2 Hours: A Prehospital Mobile Stroke Unit Study

Ritvij Bowry

,

Stephanie A. Parker

,

Patti Bratina

,

Noopur Singh

,

Jose-Miguel Yamal

,

Suja S. Rajan

,

Asha P. Jacob

,

Kenny Phan

,

Alexandra Czap

and

James C. Grotta

Stroke. 2022 | Volume 53, Issue 7: 2352–2360,

originally publishedApril 4, 2022,

https://doi.org/10.1161/STROKEAHA.121.037591

Abstract Export Citations PDF/EPUB

Background:
Hematoma enlargement (HE) after intracerebral hemorrhage (ICH) is a therapeutic target for improving outcomes. Hemostatic therapies to prevent HE may be more effective the earlier they are attempted. An understanding of HE in first 1 to 2 hours specifically in the prehospital setting would help guide future treatment interventions in this time frame and setting.

Methods:
Patients with spontaneous ICH within 4 hours of symptom onset were prospectively evaluated between May 2014 and April 2020 as a prespecified substudy within a multicenter trial of prehospital mobile stroke unit versus standard management. Baseline computed tomography scans obtained <1, 1 to 2, and 2 to 4 hours postsymptom onset on the mobile stroke unit in the prehospital setting were compared with computed tomography scans repeated 1 hour later and at 24 hours in the hospital. HE was defined as >6 mL if baseline ICH volume was <20 mL and 33% increase if baseline volume >20 mL. The association between time from symptom onset to baseline computed tomography (hours) and HE was investigated using Wilcoxon rank-sum test when time was treated as a continuous variable and using Fisher exact test when time was categorized. Kruskal-Wallis and Wilcoxon rank-sum tests evaluated differences in baseline volumes and HE. Univariable and multivariable logistic regression analyses were conducted to identify factors associated with HE and variable selection was performed using cross-validated L1-regularized (Lasso regression). This study adhered to STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology) for cohort studies.

Results:
One hundred thirty-nine patients were included. There was no difference between baseline ICH volumes obtained <1 hour (n=43) versus 1 to 2 hour (n=51) versus >2 hours (n=45) from symptom onset (median [interquartile range], 13 mL [6–24] versus 14 mL [6–30] versus 12 mL [4–19]; P=0.65). However, within the same 3 time epochs, initial hematoma growth (volume/time from onset) was greater with earlier baseline scanning (median [interquartile range], 17 mL/hour [9–35] versus 9 mL/hour [5–23]) versus 4 mL/hour [2–7]; P<0.001). Forty-nine patients had repeat scans 1 hour after baseline imaging (median, 2.3 hours [interquartile range. 1.9–3.1] after symptom onset). Eight patients (16%) had HE during that 1-hour interval; all of these occurred in patients with baseline imaging within 2 hours of onset (5/18=28% with baseline imaging within 1 hour, 3/18=17% within 1–2 hour, 0/13=0% >2 hours; P=0.02). HE did not occur between the scans repeated at 1 hour and 24 hours. No association between baseline variables and HE was detected in multivariable analyses.

Conclusions:
HE in the next hour occurs in 28% of ICH patients with baseline imaging within the first hour after symptom onset, and in 17% of those with baseline imaging between 1 and 2 hours. These patients would be a target for ultraearly hemostatic intervention. Graphical Abstract

Evidence of Motor Skill Learning in Acute Stroke Patients Without Lesions to the Thalamus and Internal Capsule

Audrey Riga

,

Estelle Gathy

,

Marisa Ghinet

,

Chloë De Laet

,

Benoît Bihin

,

Maxime Regnier

,

Maria Leeuwerck

,

Béatrice De Coene

,

Laurence Dricot

,

Benoît Herman

,

Martin G. Edwards

and

Yves Vandermeeren

Stroke. 2022 | Volume 53, Issue 7: 2361–2368,

originally publishedMarch 21, 2022,

https://doi.org/10.1161/STROKEAHA.121.035494

Abstract Export Citations PDF/EPUB

Background:
It is currently unknown whether motor skill learning (MSkL) with the paretic upper limb is possible during the acute phase after stroke and whether lesion localization impacts MSkL. Here, we investigated MSkL in acute (1–7 days post) stroke patients compared with healthy individuals (HIs) and in relation to voxel-based lesion symptom mapping.

Methods:
Twenty patients with acute stroke and 35 HIs were trained over 3 consecutive days on a neurorehabilitation robot measuring speed, accuracy, and movement smoothness variables. Patients used their paretic upper limb and HI used their nondominant upper limb on an MSkL task involving a speed/accuracy trade-off. Generalization was evaluated on day 3. All patients underwent a 3-dimensional magnetic resonance imaging used for VSLM.

Results:
Most patients achieved MSkL demonstrated by day-to-day retention and generalization of the newly learned skill on day 3. When comparing raw speed/accuracy trade-off values, HI achieved larger MSkL than patients. However, relative speed/accuracy trade-off values showed no significant differences in MSkL between patients and HI on day 3. In patients, MSkL progression correlated with acute motor and cognitive impairments. The voxel-based lesion symptom mapping showed that acute vascular damage to the thalamus or the posterior limb of the internal capsule reduced MSkL.

Conclusions:
Despite worse motor performance for acute stroke patients compared with HI, most patients were able to achieve MSkL with their paretic upper limb. Damage to the thalamus and posterior limb of the internal capsule, however, reduced MSkL. These data show that MSkL could be implemented into neurorehabilitation during the acute phase of stroke, particularly for patients without lesions to the thalamus and posterior limb of the internal capsule.

Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT01519843. Graphical Abstract

Rho-Kinase Inhibition Improves the Outcome of Focal Subcortical White Matter Lesions

Sanem A. Aykan

,

Hongyu Xie

,

Yi Zheng

,

David Y. Chung

,

Sreekanth Kura

,

James Han Lai

,

Taylan D. Erdogan

,

Andreia Morais

,

Isra Tamim

,

Damla Yagmur

,

Hidehiro Ishikawa

,

Ken Arai

,

M. Abbas Yaseen

,

David A. Boas

,

Sava Sakadzic

and

Cenk Ayata

Stroke. 2022 | Volume 53, Issue 7: 2369–2376,

originally publishedJune 3, 2022,

https://doi.org/10.1161/STROKEAHA.121.037358

Abstract Export Citations PDF/EPUB

Background:
Subcortical white matter lesions are exceedingly common in cerebral small vessel disease and lead to significant cumulative disability without an available treatment. Here, we tested a rho-kinase inhibitor on functional recovery after focal white matter injury.

Methods:
A focal corpus callosum lesion was induced by stereotactic injection of N⁵-(1-iminoethyl)-L-ornithine in mice. Fasudil (10 mg/kg) or vehicle was administered daily for 2 weeks, starting one day after lesion induction. Resting-state functional connectivity and grid walk performance were studied longitudinally, and lesion volumes were determined at one month.

Results:
Resting-state interhemispheric functional connectivity significantly recovered between days 1 and 14 in the fasudil group (P<0.001), despite worse initial connectivity loss than vehicle before treatment onset. Grid walk test revealed an increased number of foot faults in the vehicle group compared with baseline, which persisted for at least 4 weeks. In contrast, the fasudil arm did not show an increase in foot faults and had smaller lesions at 4 weeks. Immunohistochemical examination of reactive astrocytosis, synaptic density, and mature oligodendrocytes did not reveal a significant difference between treatment arms.

Conclusions:
These data show that delayed fasudil posttreatment improves functional outcomes after a focal subcortical white matter lesion in mice. Future work will aim to elucidate the mechanisms. Graphical Abstract

Delayed Infiltration of Peripheral Monocyte Contributes to Phagocytosis and Transneuronal Degeneration in Chronic Stroke

Keun Woo Park

,

Hyunwoo Ju

,

Il-doo Kim

,

John W. Cave

,

Yang Guo

,

Wei Wang

,

Zhuhao Wu

and

Sunghee Cho

Stroke. 2022 | Volume 53, Issue 7: 2377–2388,

originally publishedJune 3, 2022,

https://doi.org/10.1161/STROKEAHA.122.038701

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Background:
Mononuclear phagocytes, including monocyte-derived macrophages (MDMs) and microglia, contribute to infarct development as well as tissue repair in the postischemic brain. Here, we identify the origin and function of MDMs in the brain during poststroke repair processes.

Methods:
Adult mice were subjected to transient middle cerebral artery occlusion. Longitudinal brain atrophy and secondary degeneration were evaluated during acute to recovery phases of stroke. Adoptive transfer of GFP+ splenocytes into asplenic mice was used to distinguish MDMs from resident microglia. Fluorescence beads were injected into stroked animals to examine phagocytic function.

Results:
Progressive atrophy and neuronal degeneration in remote regions were observed in chronic stroke, which also was accompanied by MDM infiltration into the ipsilateral hemisphere. Compared with microglia, MDMs had significantly higher phagocytic activity. MDM trafficking and phagocytosis was spatiotemporally regulated with acute and prolonged infiltration into infarcted tissue, as well as delayed entry in remote areas such as the thalamus and substantia nigra.

Conclusions:
The stepwise and long-lasting involvement of MDMs at multiple poststroke stages shows that MDMs have a role in progressive stroke-induced injury and repair processes. These findings suggest that manipulating monocyte entry at different stroke stages may be an effective immune-based strategy to limit injury propagation in chronic stroke. Graphical Abstract

Effect of Intensive Blood Pressure Control on Incident Stroke Risk in Patients With Mild Cognitive Impairment

Adam de Havenon

,

Richa Sharma

,

Guido J. Falcone

,

Shyam Prabhakaran

and

Kevin N. Sheth

Stroke. 2022 | Volume 53, Issue 7: e242–e245,

originally publishedMay 3, 2022,

https://doi.org/10.1161/STROKEAHA.122.038818

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Background:
Patients with mild cognitive impairment may be at higher risk of incident stroke, but the effect of intensive blood pressure (BP) control on that risk has not been explored.

Methods:
We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) and included patients with a baseline Montreal Cognitive Assessment score of 19 to 25 and without a prior history of stroke. The primary outcome was incident stroke (ischemic and hemorrhagic) during follow-up. We report the unadjusted cumulative risk of our primary outcome by SPRINT randomization arm (intensive versus standard BP control) and also fit Cox models to the primary outcome and adjusted for patient age at randomization, race/ethnicity, sex, baseline BP, atrial fibrillation, diabetes, and smoking.

Results:
We included 5091 patients (mean age 68.2, 44% female, 56.7% non-Hispanic White, and 50.2% randomized to intensive BP control), of which 95/5091 (1.9%) had an incident stroke during a mean of 3.8±0.9 years of follow-up. The risk of incident stroke in patients randomized to standard BP control was 57/2536 (2.3%) and to intensive BP control was 38/2555 (1.5%; P=0.045). In the adjusted Cox model, the hazard ratio for incident stroke events with intensive BP control was 0.65 (95% CI, 0.43–0.98; P=0.040).

Conclusions:
Although the SPRINT trial failed to show a reduction in stroke with intensive BP control for all subjects, those with a Montreal Cognitive Assessment score consistent with mild cognitive impairment at baseline had an association between intensive BP control and lower risk of incident stroke. Future trials of primary prevention of stroke may benefit from enrichment using baseline vascular biomarkers of elevated risk, such as mild cognitive impairment. Graphical Abstract

Reliability of Instant Messaging-Based Evaluation of Brain Imaging in Acute Stroke

Love-Preet Kalra

,

Himani Khatter

,

Anirudh Kulkarni

,

Rajeshwar Sahonta

,

Shubhra Rathore

,

Elke Hattingen

,

Se-Jong You

,

Marlies Wagner

,

Stefan Weidauer

,

Fee Keil

,

Jeyaraj Durai Pandian

and

Christian Foerch

Stroke. 2022 | Volume 53, Issue 7: e246–e250,

originally publishedMay 4, 2022,

https://doi.org/10.1161/STROKEAHA.121.037274

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Background:
The use of instant messenger applications among physicians has become common in acute stroke management, especially in developing countries. Photos or video sequences of brain computed tomography (CT) scans are being sent to receive real-time support in assessing radiological findings. We analyzed whether instant messaging-based evaluation is precise enough to extract relevant information from the images.

Methods:
In this prospective study, anonymized videos and photos of CT and CT angiography scans of patients with symptoms of acute stroke were recorded from the diagnostic monitor using a smartphone. Two neurologists and 2 neuroradiologists performed evaluation of the images using WhatsApp. The gold standard was set by 2 experienced neuroradiologists who evaluated the CT images with their full radiological equipment. Statistical analysis included the calculation of Cohen kappa (κ).

Results:
A total of 104 brain images (derived from 81 patients) were included. All 4 raters performed with a perfect (κ=1) interobserver reliability in diagnosing intracerebral hemorrhage. For subarachnoid hemorrhage, interobserver reliability was slightly lower (raters 1, 2, and 3, κ=1; rater 4, κ=0.88). For diagnosing stroke mimics, interobserver reliability showed considerable variations (κ between 0.32 and 1). Alberta Stroke Program Early CT Score differences overall were comparable between raters and did not exceed 3 to 4 points without noticeable outliers. All raters performed with a moderate-to-substantial interobserver reliability for detecting large vessel occlusions (κ=0.48 in rater 1, κ=0.62 in rater 2, and κ=0.63 in raters 3 and 4).

Conclusions:
Stroke neurologists can reliably extract information on intracerebral hemorrhage from CT images recorded via smartphone and sent through instant messaging tools. Remote diagnosis of early infarct signs and stroke mimics was less reliable. We developed a standard for the acquisition of images, taking data protection into account. Graphical Abstract

Detecting Silent Acute Microinfarcts in Cerebral Small Vessel Disease Using Submillimeter Diffusion-Weighted Magnetic Resonance Imaging: Preliminary Results

Karen Misquitta

,

Marietou Daou

,

John Conklin

,

Congyu Liao

,

Kawin Setsompop

,

Julien Poublanc

,

Zahra Shirzadi

,

Bradley J. MacIntosh

,

George Tomlinson

,

Melanie Cohn

,

Richard I. Aviv

,

Frank L. Silver

and

Daniel M. Mandell

Stroke. 2022 | Volume 53, Issue 7: e251–e252,

originally publishedJune 13, 2022,

https://doi.org/10.1161/STROKEAHA.122.039723

Thrombosed Developmental Venous Anomaly as a Rare Cause of Brain Stem Venous Infarction

Stephanie B. Syc-Mazurek

,

Nathan A. Seven

,

Saumya M. Shah

,

John J. Chen

and

Zafer Keser

Stroke. 2022 | Volume 53, Issue 7: e253–e254,

originally publishedMay 6, 2022,

https://doi.org/10.1161/STROKEAHA.122.038314

COVID-19-Associated Cerebral Developmental Venous Anomaly Thrombosis With Hemorrhagic Transformation

Stephano J. Chang

,

Alexander D. Rebchuk

,

Philip Teal

,

Christopher R. Honey

and

Thalia S. Field

Stroke. 2022 | Volume 53, Issue 7: e255–e256,

originally publishedMay 25, 2022,

https://doi.org/10.1161/STROKEAHA.122.039534

Congenital Left Ventricular Diverticulum: A Rare Cause of Recurrent Juvenile Cryptogenic Stroke

Marina Romozzi

,

Valeria Guglielmino

,

Costanza Sottani

,

Aldobrando Broccolini

and

Mauro Monforte

Stroke. 2022 | Volume 53, Issue 7: e257–e258,

originally publishedMay 13, 2022,

https://doi.org/10.1161/STROKEAHA.122.039578

Role of Endothelial Cells and Platelets in COVID-Related Cerebrovascular Events

Nabil J. Alkayed

and

Marilyn J. Cipolla

Stroke. 2022 | Volume 53, Issue 7: 2389–2392,

originally publishedJune 8, 2022,

https://doi.org/10.1161/STROKEAHA.122.039971

Accuracy of Automated Computer-Aided Diagnosis for Stroke Imaging: A Critical Evaluation of Current Evidence

Joanna M. Wardlaw

,

Grant Mair

,

Rüdiger von Kummer

,

Michelle C. Williams

,

Wenwen Li

,

Amos J. Storkey

,

Emanuel Trucco

,

David S. Liebeskind

,

Andrew Farrall

,

Philip M. Bath

and

Philip White

Stroke. 2022 | Volume 53, Issue 7: 2393–2403,

originally publishedApril 20, 2022,

https://doi.org/10.1161/STROKEAHA.121.036204

Abstract Export Citations PDF/EPUB
There is increasing interest in computer applications, using artificial intelligence methodologies, to perform health care tasks previously performed by humans, particularly in medical imaging for diagnosis. In stroke, there are now commercial artificial intelligence software for use with computed tomography or MR imaging to identify acute ischemic brain tissue pathology, arterial obstruction on computed tomography angiography or as hyperattenuated arteries on computed tomography, brain hemorrhage, or size of perfusion defects. A rapid, accurate diagnosis may aid treatment decisions for individual patients and could improve outcome if it leads to effective and safe treatment; or conversely, to disaster if a delayed or incorrect diagnosis results in inappropriate treatment. Despite this potential clinical impact, diagnostic tools including artificial intelligence methods are not subjected to the same clinical evaluation standards as are mandatory for drugs. Here, we provide an evidence-based review of the pros and cons of commercially available automated methods for medical imaging diagnosis, including those based on artificial intelligence, to diagnose acute brain pathology on computed tomography or magnetic resonance imaging in patients with stroke.

Impact of Exercise on Cerebrovascular Physiology and Risk of Stroke

Justin A. Edward

and

William K. Cornwell III

Stroke. 2022 | Volume 53, Issue 7: 2404–2410,

originally publishedMay 4, 2022,

https://doi.org/10.1161/STROKEAHA.121.037343

Abstract Export Citations PDF/EPUB
Ischemic heart disease and stroke are the number 1 and number 2 causes of death worldwide, respectively. A lifelong commitment to exercise reduces the risk of these adverse events and is also associated with several cardiometabolic improvements, including reductions in blood pressure, cholesterol, and inflammatory markers, as well as improved glucose control. Routine exercise also reduces the risk of developing comorbidities that increase the risk of cardiovascular or cerebrovascular disease. While the benefits of a lifelong commitment to exercise are well documented, there is a complex interaction between exercise and stroke risk, such that the risk of ischemic or hemorrhagic stroke may increase acutely during or immediately following exercise. In this article, we discuss the physiological responses to different types of exercise, as well as the determinants of resting and exertional cerebrovascular perfusion, and explore the complex interaction between atrial fibrillation, exercise, and stroke risk. Finally, we highlight the increased risk of stroke during different types of exercise, as well as factors that may alleviate this risk.

Perspective: The Case for Acute Large Vessel Ischemic Stroke in COVID-19 Originating Within Thrombosed Pulmonary Venules

James F.M. Meaney

,

James S. O’Donnell

,

Charles Bridgewood

,

Joseph Harbison

and

Dennis McGonagle

Stroke. 2022 | Volume 53, Issue 7: 2411–2419,

originally publishedMay 11, 2022,

https://doi.org/10.1161/STROKEAHA.121.038056

Abstract Export Citations PDF/EPUB
The main burden of SARS-CoV-2 falls on the lungs but neurological manifestations, the most disabling of which are strokes and which correlate with disease severity, are common. We proffer a novel mechanism for acute COVID-19 stroke whereby pulmonary vein clots developing within the characteristic pulmonary intravascular thrombotic lesions can embolize to the brain. Appreciation of this mechanism requires an understanding of the tricompartmental model of lung parenchyma oxygenation (the alveolus, the bronchial artery, and the pulmonary artery), all of which are compromised in COVID-19. Of these 3 sources, the bronchial artery plays a crucial role in COVID-19 stroke because the unique collaterals from bronchial artery to pulmonary vein which exist under normal physiological conditions (and which maintain venous patency when the pulmonary artery is blocked by embolus) are occluded, thus leading to venular thrombosis in the presence of hypercoagulability. Dislodgement of clots from this source translocates the pathology to the brain and is a disease mechanism, formerly rare, which may account for many cases of large vessel occlusion stroke in COVID-19. This mechanism extends the concept of cardioembolic stroke from endocardium retrogradely into the pulmonary circulation with which the left cardiac chambers lie in direct continuity, and which is an accepted stroke mechanism under other circumstances such as lung lobectomy, where surgical ligation of the pulmonary vein creates a blind sac from which thrombi can embolize. The proposed model is supported by postmortem studies which have demonstrated venular thrombosis and by case reports of pulmonary vein thrombosis in COVID-19. This concept provides a more plausible cause for COVID-19 associated large vessel occlusion stroke than other putative mechanisms, such as cerebral endotheliitis, cytokine storm, and hypercoagulopathy, although it is acknowledged that the latter mechanism contributes to the genesis of pulmonary vein clots. Recognizing that extrapulmonary manifestations including stroke arise within thrombosed pulmonary veins is key to understanding of neurological manifestations of SARS-CoV-2 infection.

Ethical Justification for Deferral of Consent in the AcT Trial for Acute Ischemic Stroke

Hannah Faris

,

Brian Dewar

,

Dar Dowlatshahi

,

Alnar Ramji

,

Carol Kenney

,

Stacey Page

,

Brian Buck

,

Michael D. Hill

,

Shelagh B. Coutts

,

Mohammed Almekhlafi

,

Tolulope Sajobi

,

Nishita Singh

,

Arshia Sehgal

,

Richard H. Swartz

,

Bijoy K. Menon

and

Michel Shamy

Stroke. 2022 | Volume 53, Issue 7: 2420–2423,

originally publishedMay 23, 2022,

https://doi.org/10.1161/STROKEAHA.122.038760

Abstract Export Citations PDF/EPUB
The AcT trial (Alteplase Compared to Tenecteplase) compares alteplase or tenecteplase for patients with acute ischemic stroke. All eligible patients are enrolled by deferral of consent. Although the use of deferral of consent in the AcT trial meets the requirements of Canadian policy, we sought to provide a more explicit and rigorous approach to the justification of deferral of consent organized around 3 questions. Ultimately, the approach we outline here could become the foundation for a general justification for deferral of consent.

Carotid Sources of Stroke

J.P. Mohr

Stroke. 2022 | Volume 53, Issue 7: e259–e263,

originally publishedJune 27, 2022,

https://doi.org/10.1161/STROKEAHA.122.038567

Abstract Export Citations PDF/EPUB
The ancient Greeks used the term karotides for the great arteries in the neck, compression of which could plunge the victim into karoun: deep sleep or stupor. The artery name aside, studies of the patterns of brain infarction and their clinical severity have been an unbroken chain of growing sophistication in the past 150 years. Two main patterns emerged: perfusion failure with high-convexity infarction from hemodynamically important ipsilateral carotid stenosis or embolism from nonstenosing carotid plaque.

Organizational Update: World Stroke Conference 2021

Ana Catarina Fonseca

and

Sean I. Savitz

Stroke. 2022 | Volume 53, Issue 7: e264–e266,

originally publishedJune 27, 2022,

https://doi.org/10.1161/STROKEAHA.122.038782

Local Versus General Anesthesia for Carotid Endarterectomy: Cochrane Review

Amaraporn Rerkasem

,

Sothida Nantakool

,

Saritphat Orrapin

,

Peter M. Rothwell

,

Dominic P.J. Howard

and

Kittipan Rerkasem

Stroke. 2022 | Volume 53, Issue 7: e267–e268,

originally publishedJune 27, 2022,

https://doi.org/10.1161/STROKEAHA.121.038012

Information Provision for Stroke Survivors and Their Carers: Cochrane Review

Thomas F. Crocker

,

Lesley Brown

,

Natalie Lam

,

Faye Wray

,

Peter Knapp

and

Anne Forster

Stroke. 2022 | Volume 53, Issue 7: e269–e270,

originally publishedJune 27, 2022,

https://doi.org/10.1161/STROKEAHA.121.038162

July Literature Synopsis

Terence J. Quinn

Stroke. 2022 | Volume 53, Issue 7: e271–e272,

originally publishedJune 27, 2022,

https://doi.org/10.1161/STROKEAHA.122.039585

Write With the Reviewers in Mind: Why You Got a Rejection and How to Avoid the Next

Joseph Kamtchum-Tatuene

,

Larissa Ange Tchuisseu-Kwangoua

,

Noëlle Audrey Moko-Tatuene

,

Jean Joel Bigna

and

Jean Jacques Noubiap

Stroke. 2022 | Volume 53, Issue 7: e273–e275,

originally publishedMarch 28, 2022,

https://doi.org/10.1161/STROKEAHA.122.036142

Persistent Posterior Fossa Hypoperfusion in the Setting of Vertebrobasilar Dolichoectasia

Peter S.W. Park

,

Vignan Yogendrakumar

,

Nawaf Yassi

and

Bruce C.V. Campbell

Stroke. 2022 | Volume 53, Issue 7: e276–e281,

originally publishedMay 27, 2022,

https://doi.org/10.1161/STROKEAHA.122.038527

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association

Steven M. Greenberg

,

Wendy C. Ziai

,

Charlotte Cordonnier

,

Dar Dowlatshahi

,

Brandon Francis

,

Joshua N. Goldstein

,

J. Claude Hemphill III

,

Ronda Johnson

,

Kiffon M. Keigher

,

William J. Mack

,

J. Mocco

,

Eileena J. Newton

,

Ilana M. Ruff

,

Lauren H. Sansing

,

Sam Schulman

,

Magdy H. Selim

,

Kevin N. Sheth

,

Nikola Sprigg

,

Katharina S. Sunnerhagen

and

on behalf of the American Heart Association/American Stroke Association

Stroke. 2022 | Volume 53, Issue 7: e282–e361,

originally publishedMay 17, 2022,

https://doi.org/10.1161/STR.0000000000000407

Correction to: Clinical Results of the Advanced Neurovascular Access Catheter System Combined With a Stent Retriever in Acute Ischemic Stroke (SOLONDA)

Stroke. 2022 | Volume 53, Issue 7: e362,

originally publishedJune 27, 2022,

https://doi.org/10.1161/STR.0000000000000409

This article corrects the following:
- Clinical Results of the Advanced Neurovascular Access Catheter System Combined With a Stent Retriever in Acute Ischemic Stroke (SOLONDA)
  - Manuel Requena
  - Marc Ribo
  - Joaquin Zamarro
  - Pedro Vega
  - Jordi Blasco
  - Eva María González
  - María Del Mar Freijo
  - Jose Carlos Mendez Cendón
  - María Ángeles de Miquel
  - David Hernández
  - Manuel Moreu
  - Sebastià Remollo
  - Sonia Sánchez
  - David S. Liebeskind
  - Tommy Andersson
  - Christophe Cognard
  - Raul Nogueira
  - Alejandro Tomasello
  - Volume 53Issue 7Stroke
  - 1 April 2022

Table of Contents

Stroke: Highlights of Selected Articles

July 2022 Stroke Highlights

Focused Updates

Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities

Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

Cardiovascular Events After Intracerebral Hemorrhage

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities

Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

Cardiovascular Events After Intracerebral Hemorrhage

Cardiovascular Events After Intracerebral Hemorrhage

Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities

Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities

Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities

Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage

Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

Cardiovascular Events After Intracerebral Hemorrhage

Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage

Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

Cardiovascular Events After Intracerebral Hemorrhage

Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation

Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

Cardiovascular Events After Intracerebral Hemorrhage

Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

Cardiovascular Events After Intracerebral Hemorrhage

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities

Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation

Cardiovascular Events After Intracerebral Hemorrhage

Focused Update on Vascular Risk and Secondary Prevention in Survivors of Intracerebral Hemorrhage

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities

Protecting the Brain, From the Heart: Safely Mitigating the Consequences of Thrombosis in Intracerebral Hemorrhage Survivors With Atrial Fibrillation

Cardiovascular Events After Intracerebral Hemorrhage

Clinical Trials

Priming Intermittent Theta Burst Stimulation for Hemiparetic Upper Limb After Stroke: A Randomized Controlled Trial

Background:

Methods:

Results:

Conclusions:

Registration:

Robot-Assisted Training as Self-Training for Upper-Limb Hemiplegia in Chronic Stroke: A Randomized Controlled Trial

Background:

Methods:

Results:

Conclusions:

Registration:

Tailored Sitting Tai Chi Program for Subacute Stroke Survivors: A Randomized Controlled Trial

Background:

Methods:

Results:

Conclusions:

Registration:

Effect of Deferoxamine on Trajectory of Recovery After Intracerebral Hemorrhage: A Post Hoc Analysis of the i-DEF Trial

Background:

Methods:

Results:

Conclusions:

Registration:

Clinical Results of the Advanced Neurovascular Access Catheter System Combined With a Stent Retriever in Acute Ischemic Stroke (SOLONDA)

Correction to: Clinical Results of the Advanced Neurovascular Access Catheter System Combined With a Stent Retriever in Acute Ischemic Stroke (SOLONDA)

Background:

Methods:

Results:

Conclusions: