Non-invasive Brain Stimulation Can Reduce Unilateral Spatial Neglect after Stroke: ELETRON Trial.

OBJECTIVE: Rehabilitation top-down techniques based on brain stimulation present variable outcomes in unilateral spatial neglect (USN) after stroke. This study aimed to examine the effects of physical therapy after anodal and cathodal transcranial direct current stimulation (A-tDCS and C-tDCS, respectively) to improve visuospatial and functional impairments in individuals with USN after stroke. METHODS: This double-blinded, pilot randomized clinical trial enrolled patients with USN after ischemic stroke. Randomization was stratified according to the Behavior Inattention Test-Conventional (BIT-C) and Catherine Bergego Scale (CBS). Outpatient physical therapy was conducted for 7.5 weeks after 20 minutes of tDCS. The primary outcome was the USN degree evaluated by the BIT-C. Secondary outcomes were the difference in CBS score, stroke severity (National Institutes of Health Stroke Scale [NIHSS]), disability (modified Rankin Scale), autonomy (Barthel Index, Functional Independence Measure), and quality of life (EuroQol Group 5-Dimension Self-Report Questionnaire). Outcomes were analyzed using an analysis of covariance model corrected by age, baseline NIHSS, and baseline BIT-C. Pairwise post hoc comparisons were performed using Bonferroni correction. RESULTS: In the primary outcomes, A-tDCS led to greater improvement in BIT-C after intervention (mean difference [MD] = 18.4, 95% confidence interval [CI] = 3.9-32.8, p = 0.008) compared to sham. However, no significant differences were observed between A-tDCS and C-tDCS (MD = 13.9, 95% CI = -0.3 to 28.1, p = 0.057), or C-tDCS and sham (MD = 4.5, 95% CI = -9.7 to 18.8, p = 0.99). There were no significant differences between groups in terms of secondary outcomes. INTERPRETATION: A-tDCS associated with physical therapy can decrease the severity of USN after stroke. However, these preliminary findings must be confirmed by collecting additional evidence in a larger phase 3 trial. ANN NEUROL 2022;92:400-410.

Site matters: Central neuropathic pain characteristics and somatosensory findings after brain and spinal cord lesions.

BACKGROUND: It is unknown if different etiologies or lesion topographies influence central neuropathic pain (CNP) clinical manifestation. METHODS: We explored the symptom-somatosensory profile relationships in CNP patients with different types of lesions to the central nervous system to gain insight into CNP mechanisms. We compared the CNP profile through pain descriptors, standardized bedside examination, and quantitative sensory test in two different etiologies with segregated lesion locations: the brain, central poststroke pain (CPSP, n = 39), and the spinal cord central pain due to spinal cord injury (CPSCI, n = 40) in neuromyelitis optica. RESULTS: Results are expressed as median (25th to 75th percentiles). CPSP presented higher evoked and paroxysmal pain scores compared to CPSCI (p < 0.001), and lower cold thermal limen (5.6°C [0.0-12.9]) compared to CPSCI (20.0°C [4.2-22.9]; p = 0.004). CPSCI also had higher mechanical pain thresholds (784.5 mN [255.0-1078.0]) compared to CPSP (235.2 mN [81.4-1078.0], p = 0.006) and higher mechanical detection threshold compared to control areas (2.7 [1.5-6.2] vs. 1.0 [1.0-3.3], p = 0.007). Evoked pain scores negatively correlated with mechanical pain thresholds (r = -0.38, p < 0.001) and wind-up ratio (r = -0.57, p < 0.001). CONCLUSIONS: CNP of different etiologies may present different pain descriptors and somatosensory profiles, which is likely due to injury site differences within the neuroaxis. This information may help better design phenotype mechanism correlations and impact trial designs for the main etiologies of CNP, namely stroke and spinal cord lesions. This study provides evidence that topography may influence pain symptoms and sensory profile. The findings suggest that CNP mechanisms might vary according to pain etiology or lesion topography, impacting future mechanism-based treatment choices.

Headache at the chronic stage of cerebral venous thrombosis.

BACKGROUND: Headache is the most frequent symptom of cerebral venous thrombosis (CVT) but there is limited information about the frequency and phenotype of headache, weeks to months after cerebral venous thrombosis (post-cerebral venous thrombosis headache, PCH). OBJECTIVE: To assess the frequency, characteristics and predictors of PCH. METHODS: In this cross-sectional study, the frequency and characteristics of PCH were assessed in cerebral venous thrombosis survivors. Patients were interviewed between six months and five years after the cerebral venous thrombosis diagnosis. Clinical and imaging characteristics at the time of cerebral venous thrombosis diagnosis, as well as history of headache prior to cerebral venous thrombosis were compared in subjects with (GroupPCH) and without PCH (Groupcontrol). RESULTS: Subjects (n = 100; 82% women) were assessed, on average, at 1.1 ± 1.6 years of follow-up. PCH was present in 59% of the patients, phenotypes of tension-type-like headache were present in 31/59 (52.6%) and of migraine-like headache in 16/59 (27.1%). History of primary headache prior to cerebral venous thrombosis was significantly more common (OR: 6.4; 95% CI: 1.7-36.3) in GroupPCH (33.9%) than in Groupcontrol (7.3%). CONCLUSION: PCH was present in more than half of the patients. History of prior headache may be a risk factor for PCH. Prospective studies are required to confirm these findings and determine mechanisms, as well as interventions for prevention and treatment of PCH.

Outcomes of acute basilar artery occlusion-real-world experience in a middle-income country.

OBJECTIVES: Our goal was to describe outcomes in a single-center, real-world series of patients with acute basilar artery occlusion in a middle-income country. In addition, we assessed potential outcome predictors. MATERIAL AND METHODS: Data from 28 patients were retrospectively reviewed. The primary outcome was death until last follow-up. Other outcomes were rates of favorable outcome until last follow-up and rates of intracranial hemorrhage. Outcomes were compared in subgroups according to several variables, including reperfusion (REP group) or no reperfusion (NOREP group) interventions, with chi-squared, Fisher's exact test, or Mann-Whitney tests. RESULTS: The rate of overall intrahospital death was 46%. Death until last follow-up occurred in 8/17 (47%) in the REP and in 7/11 (63%) of the NOREP group. Favorable outcomes were observed in 35.7% of the patients: 8/17 (47%) in REP and in 2/11 (18.1%) in NOREP. NIH stroke scale scores were significantly lower in patients with favorable outcomes. Intracranial hemorrhage was observed in 6/28 (21.4%) of the patients (all in REP group). Twenty patients were treated with anticoagulants within the first 24 h. No hemorrhage was observed in those treated with enoxaparin, while three occurred in subjects treated with unfractionated heparin. CONCLUSION: Together with other series, our results underscore the relevance of NIH stroke scale at admission as a prognostic marker, the importance of reperfusion to improve outcomes, and the need of clinical trials to compare the impact of treatment with anticoagulants within first 24 h in basilar artery occlusion.

Noninvasive Brain Stimulations for Unilateral Spatial Neglect after Stroke: A Systematic Review and Meta-Analysis of Randomized and Nonrandomized Controlled Trials.

Background: Unilateral spatial neglect (USN) is the most frequent perceptual disorder after stroke. Noninvasive brain stimulation (NIBS) is a tool that has been used in the rehabilitation process to modify cortical excitability and improve perception and functional capacity. Objective: To assess the impact of NIBS on USN after stroke. Methods: An extensive search was conducted up to July 2016. Studies were selected if they were controlled and noncontrolled trials examining transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and theta burst stimulation (TBS) in USN after stroke, with outcomes measured by standardized USN and functional tests. Results: Twelve RCTs (273 participants) and 4 non-RCTs (94 participants) proved eligible. We observed a benefit in overall USN measured by the line bisection test with NIBS in comparison to sham (SMD -2.35, 95% CI -3.72, -0.98; p = 0.0001); the rTMS yielded results that were consistent with the overall meta-analysis (SMD -2.82, 95% CI -3.66, -1.98; p = 0.09). The rTMS compared with sham also suggested a benefit in overall USN measured by Motor-Free Visual Perception Test at both 1 Hz (SMD 1.46, 95% CI 0.73, 2.20; p < 0.0001) and 10 Hz (SMD 1.19, 95% CI 0.48, 1.89; p = 0.54). There was also a benefit in overall USN measured by Albert's test and the line crossing test with 1 Hz rTMS compared to sham (SMD 2.04, 95% CI 1.14, 2.95; p < 0.0001). Conclusions: The results suggest a benefit of NIBS on overall USN, and we conclude that rTMS is more efficacious compared to sham for USN after stroke.

Increase of Stroke Incidence in Young Adults in a Middle-Income Country: A 10-Year Population-Based Study.

BACKGROUND AND PURPOSE: The incidence of stroke is on the rise in young adults in high-income countries. However, there is a gap of knowledge about trends in stroke incidence in young adults from low- and middle-income countries. We aimed to measure trends in incidence of ischemic stroke (IS) and intracerebral hemorrhage (IH) in young people from 2005 to 2015 in Joinville, Brazil. METHODS: We retrospectively ascertained all first-ever IS subtypes and IH that occurred in Joinville in the periods of 2005 to 2006, 2010 to 2011, and 2014 to 2015. Poisson regression was used to calculate incidence rate ratios of all strokes, IS, and IH. We also compared the prevalence of risk factors and extension of diagnostic work-up across the 3 periods. RESULTS: For 10 years, we registered 2483 patients (7.5% aged <45 years). From 2005 to 2006 to 2014 to 2015, overall stroke incidence significantly increased by 62% (incidence rate ratios, 1.62; 95% confidence interval, 1.10-2.40) in subjects <45 years and by 29% in those <55 years (incidence rate ratios, 1.29; 95% confidence interval, 1.04-1.60). Incidence of IS increased by 66% (incidence rate ratios, 1.66; 95% confidence interval, 1.09-2.54), but there was no significant change in incidence of IH in subjects <45 years. Smoking rates decreased by 71% (odds ratio, 0.29; 95% confidence interval, 0.12-0.68). CONCLUSIONS: Stroke incidence is rising in young adults in Joinville, Brazil, because of increase in rates of ischemic but not hemorrhagic strokes. We urgently need better policies of cardiovascular prevention in the young.

Etiological Classification of Stroke in Patients with Chagas Disease Using TOAST, Causative Classification System TOAST, and ASCOD Phenotyping.

BACKGROUND: Cardioembolism is considered a major pathophysiological mechanism in patients with ischemic stroke (IS) and Chagas disease (CD). However, a previous study reported that other stroke subtypes are present in more than 40% of CD patients according to the TOAST classification. Therefore, the aim of our study was to evaluate the etiologic classification of stroke in patients with CD using the Causative Classification System (CCS), the ASCOD, and the TOAST classifications in a prospective cohort of patients. METHODS: Patients evaluated in our outpatient clinic from 2012 to 2015 with IS and CD were included and underwent full investigation for stroke etiology. TOAST, CCS TOAST, and the ASCOD classifications were compared. FINDINGS: We Included 32 patients (18 men; mean age 62.7 +/-10.1 years). A total of 93.8% had at least 1 vascular risk factor; the most frequent was hypertension (87.5%). According to TOAST, we defined 87.5% as having cardioembolic stroke, being 9.4% as large-artery atherosclerotic (LAA) and 3.1% as undetermined cause. Using the CCS TOAST, 62.5% were classified as cardioaortic embolism evident and 15.6% as possible, 6.3% as small artery occlusion evident and 3.1% as probable, and 12.5% as LAA evident. When ASCOD phenotyping was applied, atherosclerosis was present in 50.1% of patients (A1 = 6.3%, A3 = 43.8%), cardiac pathology in 84.4% (C1 = 62.5%, C2 = 15.6%, C3 = 6.3%), and small-vessel disease in 66% (S1 = 9.4%, S2 = 3.1%, S3 = 3.1%). FINDINGS: In conclusion, the use of the CCS and the ASCOD phenotyping in patients with CD confirmed a high frequency of cardioembolic IS but also showed that other etiologies are prevalent, such as large-artery atherosclerosis and small-vessel occlusion.

Upper Limb Immobilisation: A Neural Plasticity Model with Relevance to Poststroke Motor Rehabilitation.

Advances in our understanding of the neural plasticity that occurs after hemiparetic stroke have contributed to the formulation of theories of poststroke motor recovery. These theories, in turn, have underpinned contemporary motor rehabilitation strategies for treating motor deficits after stroke, such as upper limb hemiparesis. However, a relative drawback has been that, in general, these strategies are most compatible with the recovery profiles of relatively high-functioning stroke survivors and therefore do not easily translate into benefit to those individuals sustaining low-functioning upper limb hemiparesis, who otherwise have poorer residual function. For these individuals, alternative motor rehabilitation strategies are currently needed. In this paper, we will review upper limb immobilisation studies that have been conducted with healthy adult humans and animals. Then, we will discuss how the findings from these studies could inspire the creation of a neural plasticity model that is likely to be of particular relevance to the context of motor rehabilitation after stroke. For instance, as will be elaborated, such model could contribute to the development of alternative motor rehabilitation strategies for treating poststroke upper limb hemiparesis. The implications of the findings from those immobilisation studies for contemporary motor rehabilitation strategies will also be discussed and perspectives for future research in this arena will be provided as well.

Increase in Short-Interval Intracortical Facilitation of the Motor Cortex after Low-Frequency Repetitive Magnetic Stimulation of the Unaffected Hemisphere in the Subacute Phase after Stroke.

Low-frequency repetitive transcranial magnetic stimulation of the unaffected hemisphere (UH-LF-rTMS) in patients with stroke can decrease interhemispheric inhibition from the unaffected to the affected hemisphere and improve hand dexterity and strength of the paretic hand. The objective of this proof-of-principle study was to explore, for the first time, effects of UH-LF-rTMS as add-on therapy to motor rehabilitation on short-term intracortical inhibition (SICI) and intracortical facilitation (ICF) of the motor cortex of the unaffected hemisphere (M1UH) in patients with ischemic stroke. Eighteen patients were randomized to receive, immediately before rehabilitation treatment, either active or sham UH-LF-rTMS, during two weeks. Resting motor threshold (rMT), SICI, and ICF were measured in M1UH before the first session and after the last session of treatment. There was a significant increase in ICF in the active group compared to the sham group after treatment, and there was no significant differences in changes in rMT or SICI. ICF is a measure of intracortical synaptic excitability, with a relative contribution of spinal mechanisms. ICF is typically upregulated by glutamatergic agonists and downregulated by gabaergic antagonists. The observed increase in ICF in the active group, in this hypothesis-generating study, may be related to M1UH reorganization induced by UH-LF-rTMS.

Effect of transcranial direct current stimulation in the initial weeks post-stroke: a pilot randomized study.

OBJECTIVE: This study aimed at assessing the alterations in upper limb motor impairment and connectivity between motor areas following the post-stroke delivery of cathodal transcranial direct current stimulation sessions. METHODS: Modifications in the Fugl-Meyer Assessment scores, connectivity between the primary motor cortex of the unaffected and affected hemispheres, and between the primary motor and premotor cortices of the unaffected hemisphere were compared prior to and following six sessions of cathodal transcranial direct current stimulation application in 13 patients (active = 6; sham = 7); this modality targets the primary motor cortex of the unaffected hemisphere early after a stroke. RESULTS: Clinically relevant distinctions in Fugl-Meyer Assessment scores (≥9 points) were observed more frequently in the Sham Group than in the Active Group. Between-group differences in the alterations in Fugl-Meyer Assessment scores were not statistically significant (Mann-Whitney test, p=0.133). ROI-to-ROI correlations between the primary motor cortices of the affected and unaffected hemispheres post-therapeutically increased in 5/6 and 2/7 participants in the Active and Sham Groups, respectively. Between-group differences in modifications in connectivity between the aforementioned areas were not statistically significant. Motor performance enhancements were more frequent in the Sham Group compared to the Active Group. CONCLUSION: The results of this hypothesis-generating investigation suggest that heightened connectivity may not translate into early clinical benefits following a stroke and will be crucial in designing larger cohort studies to explore mechanisms underlying the impacts of this intervention. ClinicalTrials.gov Identifier: NCT02455427.

Treatment results of carotid artery stenting in a developing country.

OBJECTIVE: The purpose of this study was to investigate the details of minor complications of carotid artery stenting in a developing country. METHODS: This was a retrospective, single-center study conducted on the target group consisting of 65 symptomatic patients who underwent carotid artery stenting. We assessed technical success rate, periprocedural complication within 30 days (hypotension, bradycardia, acute kidney injury, vasospasm, a transient ischemic attack, stroke, myocardial infarction, and death), and the differences between groups with and without complications. RESULTS: Minor periprocedural complications occurred in 15 patients. In all, 8 (12.3%) had transient hypotension, 6 (9.2%) had bradycardia, 7 (10.7%) had acute kidney injury, 2 (3.1%) had vasospasm, and 1 (1.5%) had transient ischemic attack. A greater rate of minor complications was observed in women (p=0.051). CONCLUSION: The results of the carotid artery stenting procedures performed in a developing country were acceptable.

Corticomotor excitability is altered in central neuropathic pain compared with non-neuropathic pain or pain-free patients.

OBJECTIVES: Central neuropathic pain (CNP) is associated with altered corticomotor excitability (CE), which can potentially provide insights into its mechanisms. The objective of this study is to describe the CE changes that are specifically related to CNP. METHODS: We evaluated CNP associated with brain injury after stroke or spinal cord injury (SCI) due to neuromyelitis optica through a battery of CE measurements and comprehensive pain, neurological, functional, and quality of life assessments. CNP was compared to two groups of patients with the same disease: i. with non-neuropathic pain and ii. without chronic pain, matched by sex and lesion location. RESULTS: We included 163 patients (stroke=93; SCI=70: 74 had CNP, 43 had non-neuropathic pain, and 46 were pain-free). Stroke patients with CNP had lower motor evoked potential (MEP) in both affected and unaffected hemispheres compared to non- neuropathic pain and no-pain patients. Patients with CNP had lower amplitudes of MEPs (366 µV ±464 µV) than non-neuropathic (478 ±489) and no-pain (765 µV ± 880 µV) patients, p < 0.001. Short-interval intracortical inhibition (SICI) was defective (less inhibited) in patients with CNP (2.6±11.6) compared to no-pain (0.8±0.7), p = 0.021. MEPs negatively correlated with mechanical and cold-induced allodynia. Furthermore, classifying patients' results according to normative data revealed that at least 75% of patients had abnormalities in some CE parameters and confirmed MEP findings based on group analyses. DISCUSSION: CNP is associated with decreased MEPs and SICI compared to non-neuropathic pain and no-pain patients. Corticomotor excitability changes may be helpful as neurophysiological markers of the development and persistence of pain after CNS injury, as they are likely to provide insights into global CE plasticity changes occurring after CNS lesions associated with CNP.

Ischemic stroke caused by large-artery atherosclerosis: a red flag for subclinical coronary artery disease.

Background: The coronary calcium score (CAC) measured on chest computerized tomography is a risk marker of cardiac events and mortality. We compared CAC scores in two multiethnic groups without symptomatic coronary artery disease: subjects in the chronic phase after stroke or transient ischemic attack and at least one symptomatic stenosis ≥50% in the carotid or vertebrobasilar territories (Groupathero) and a control group (Groupcontrol). Methods: In this cross-sectional study, Groupathero included two subgroups: GroupExtraorIntra, with stenoses in either cervical or intracranial arteries, and GroupExtra&Intra, with stenoses in at least one cervical and one intracranial artery. Groupcontrol had no history of prior stroke/transient ischemic attacks and no stenoses ≥50% in cervical or intracranial arteries. Age and sex were comparable in all groups. Frequencies of CAC ≥100 and CAC > 0 were compared between Groupathero and Groupcontrol, as well as between GroupExtraorIntr, GroupExtra&Intra, and Groupcontrol, with bivariate logistic regressions. Multivariate analyses were also performed. Results: A total of 120 patients were included: 80 in Groupathero and 40 in Groupcontrol. CAC >0 was significantly more frequent in Groupathero (85%) than Groupcontrol (OR, 4.19; 1.74-10.07; p = 0.001). Rates of CAC ≥100 were not significantly different between Groupathero and Groupcontrol but were significantly greater in GroupExtra&Intra (n = 13) when compared to Groupcontrol (OR 4.67; 1.21-18.04; p = 0.025). In multivariate-adjusted analyses, "Groupathero" and "GroupExtra&Intra" were significantly associated with CAC. Conclusion: The frequency of coronary calcification was higher in subjects with stroke caused by large-artery atherosclerosis than in controls.

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19.

INTRODUCTION: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. PATIENTS AND METHODS: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. RESULTS: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28-54) vs 45 (28-56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28-79) vs 68 (30-125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19-62) vs 53 (20-92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. DISCUSSION AND CONCLUSIONS: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.

Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries.

BACKGROUND: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. AIMS: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. METHODS: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). RESULTS: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20-37) versus 47 (IQR 32-58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11-40]) than in HICs (44/102 [43%, 95% CI 34-53], p = 0.039). CONCLUSIONS: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.

Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.

BACKGROUND AND OBJECTIVES: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). METHODS: We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations. DISCUSSION: There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. TRIAL REGISTRATION INFORMATION: This study is registered under NCT04934020.

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. METHODS: We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (ß = 0.21; 95% CI 0.04-0.38, p = 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (ß = -0.28; 95% CI -0.41 to -0.15, p < 0.001) and across multiple domains of function (ß = -0.14; 95% CI -0.22 to -0.06, p < 0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI 3%-58%, p = 0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (odds ratio 1.04, 95% CI 1.01-1.08, p = 0.004). DISCUSSION: We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.

Consensus paper: roles of the cerebellum in motor control--the diversity of ideas on cerebellar involvement in movement.

Considerable progress has been made in developing models of cerebellar function in sensorimotor control, as well as in identifying key problems that are the focus of current investigation. In this consensus paper, we discuss the literature on the role of the cerebellar circuitry in motor control, bringing together a range of different viewpoints. The following topics are covered: oculomotor control, classical conditioning (evidence in animals and in humans), cerebellar control of motor speech, control of grip forces, control of voluntary limb movements, timing, sensorimotor synchronization, control of corticomotor excitability, control of movement-related sensory data acquisition, cerebro-cerebellar interaction in visuokinesthetic perception of hand movement, functional neuroimaging studies, and magnetoencephalographic mapping of cortico-cerebellar dynamics. While the field has yet to reach a consensus on the precise role played by the cerebellum in movement control, the literature has witnessed the emergence of broad proposals that address cerebellar function at multiple levels of analysis. This paper highlights the diversity of current opinion, providing a framework for debate and discussion on the role of this quintessential vertebrate structure.

Sonothrombolysis for acute ischemic stroke: a systematic review of randomized controlled trials.

OBJECT: Sonothrombolysis has recently been considered an emerging modality for the treatment of stroke. The purpose of the present paper was to review randomized clinical studies concerning the effects of sonothrombolysis associated with tissue plasminogen activator (tPA) on acute ischemic stroke. METHODS: Systematic searches for literature published between January 1996 and July 2011 were performed for studies regarding sonothrombolysis combined with tPA for acute ischemic stroke. Only randomized controlled trials were included. Data extraction was based on ultrasound variables, patient characteristics, and outcome variables (rate of intracranial hemorrhages and arterial recanalization). RESULTS: Four trials were included in this study; 2 trials evaluated the effect of transcranial Doppler (TCD) ultrasonography on sonothrombolysis, and 2 addressed transcranial color-coded duplex (TCCD) ultrasonography. The frequency of ultrasound waves varied from 1.8 to 2 MHz. The duration of thrombus exposure to ultrasound energy ranged from 60 to 120 minutes. Sample sizes were small, recanalization was evaluated at different time points (60 and 120 minutes), and inclusion criteria were heterogeneous. Sonothrombolysis combined with tPA did not lead to an increase in symptomatic intracranial hemorrhagic complications. Two studies demonstrated that patients treated with ultrasound combined with tPA had statistically significant higher rates of recanalization than patients treated with tPA alone. CONCLUSIONS: Despite the heterogeneity and the limitations of the reviewed studies, there is evidence that sonothrombolysis associated with tPA is a safe procedure and results in an increased rate of recanalization in the setting of acute ischemic stroke when wave frequencies and energy intensities of diagnostic ultrasound systems are used.

Plasticity of adult sensorimotor system in severe brain infarcts: challenges and opportunities.

Functional reorganization forms the critical mechanism for the recovery of function after brain damage. These processes are driven by inherent changes within the central nervous system (CNS) triggered by the insult and further depend on the neural input the recovering system is processing. Therefore these processes interact with not only the interventions a patient receives, but also the activities and behaviors a patient engages in. In recent years, a wide range of research programs has addressed the association between functional reorganization and the spontaneous and treatment-induced recovery. The bulk of this work has focused on upper-limb and hand function, and today there are new treatments available that capitalize on the neuroplasticity of the brain. However, this is only true for patients with mild to moderated impairments; for those with very limited hand function, the basic understanding is much poorer and directly translates into limited treatment opportunities for these patients. The present paper aims to highlight the knowledge gap on severe stroke with a brief summary of the literature followed by a discussion of the challenges involved in the study and treatment of severe stroke and poor long-term outcome.