Safety and Clinical Outcome of Thrombolysis in Ischaemic Stroke Using a Perfusion CT Mismatch between 3 and 6 Hours

It may be possible to thrombolyse ischaemic stroke (IS) patients up to 6 h by using penumbral imaging. We investigated whether a perfusion CT (CTP) mismatch can help to select patients for thrombolysis up to 6 h.A cohort of 254 thrombolysed IS patients was studied. 174 (69%) were thrombolysed at 0-3 h by using non-contrast CT (NCCT), and 80 (31%) at 3-6 h (35 at 3-4.5 h and 45 at 4.5-6 h) by using CTP mismatch criteria. Symptomatic intracerebral haemorrhage (SICH), the mortality and the modified Rankin Score (mRS) were assessed at 3 months. Independent determinants of outcome in patients thrombolysed between 3 and 6 h were identified.The baseline characteristics were comparable in the two groups. There were no differences in SICH (3% v 4%, p = 0.71), any ICH (7% v 9%, p = 0.61), or mortality (16% v 9%, p = 0.15) or mRS 0-2 at 3 months (55% v 54%, p = 0.96) between patients thrombolysed at 0-3 h (NCCT only) or at 3-6 h (CTP mismatch). There were no significant differences in outcome between patients thrombolysed at 3-4.5 h or 4.5-6 h. The NIHSS score was the only independent determinant of a mRS of 0-2 at 3 months (OR 0.89, 95% CI 0.82-0.97, p = 0.007) in patients treated using CTP mismatch criteria beyond 3 h.The use of a CTP mismatch model may help to guide thrombolysis decisions up to 6 h after IS onset

Isosorbide Mononitrate and Cilostazol Treatment in Patients With Symptomatic Cerebral Small Vessel Disease: The Lacunar Intervention Trial-2 (LACI-2) Randomized Clinical Trial

Importance Cerebral small vessel disease (cSVD) is a common cause of stroke (lacunar stroke), is the most common cause of vascular cognitive impairment, and impairs mobility and mood but has no specific treatment.Objective To test the feasibility, drug tolerability, safety, and effects of 1-year isosorbide mononitrate (ISMN) and cilostazol treatment on vascular, functional, and cognitive outcomes in patients with lacunar stroke.Design, Setting, and Participants The Lacunar Intervention Trial-2 (LACI-2) was an investigator-initiated, open-label, blinded end-point, randomized clinical trial with a 2 × 2 factorial design. The trial aimed to recruit 400 participants from 26 UK hospital stroke centers between February 5, 2018, and May 31, 2021, with 12-month follow-up. Included participants had clinical lacunar ischemic stroke, were independent, were aged older than 30 years, had compatible brain imaging findings, had capacity to consent, and had no contraindications to (or indications for) the study drugs. Data analysis was performed on August 12, 2022.Interventions All patients received guideline stroke prevention treatment and were randomized to ISMN (40-60 mg/d), cilostazol (200 mg/d), ISMN-cilostazol (40-60 and 200 mg/d, respectively), or no study drug.Main Outcomes The primary outcome was recruitment feasibility, including retention at 12 months. Secondary outcomes were safety (death), efficacy (composite of vascular events, dependence, cognition, and death), drug adherence, tolerability, recurrent stroke, dependence, cognitive impairment, quality of life (QOL), and hemorrhage.Results Of the 400 participants planned for this trial, 363 (90.8%) were recruited. Their median age was 64 (IQR, 56.0-72.0) years; 251 (69.1%) were men. The median time between stroke and randomization was 79 (IQR, 27.0-244.0) days. A total of 358 patients (98.6%) were retained in the study at 12 months, with 257 of 272 (94.5%) taking 50% or more of the allocated drug. Compared with those participants not receiving that particular drug, neither ISMN (adjusted hazard ratio [aHR], 0.80 [95% CI, 0.59 to 1.09]; P = .16) nor cilostazol (aHR, 0.77 [95% CI, 0.57 to 1.05]; P = .10) alone reduced the composite outcome in 297 patients. Isosorbide mononitrate reduced recurrent stroke in 353 patients (adjusted odds ratio [aOR], 0.23 [95% CI, 0.07 to 0.74]; P = .01) and cognitive impairment in 308 patients (aOR, 0.55 [95% CI, 0.36 to 0.86]; P = .008). Cilostazol reduced dependence in 320 patients (aHR, 0.31 [95% CI, 0.14 to 0.72]; P = .006). Combination ISMN-cilostazol reduced the composite (aHR, 0.58 [95% CI, 0.36 to 0.92]; P = .02), dependence (aOR, 0.14 [95% CI, 0.03 to 0.59]; P = .008), and any cognitive impairment (aOR, 0.44 [95% CI, 0.23 to 0.85]; P = .02) and improved QOL (adjusted mean difference, 0.10 [95% CI, 0.03 to 0.17]; P = .005) in 153 patients. There were no safety concerns.Conclusions and Relevance These results show that the LACI-2 trial was feasible and ISMN and cilostazol were well tolerated and safe. These agents may reduce recurrent stroke, dependence, and cognitive impairment after lacunar stroke, and they could prevent other adverse outcomes in cSVD. Therefore, both agents should be tested in large phase 3 trials.Trial Registration ClinicalTrials.gov Identifier: NCT0345159

P244 The effect of transcranial direct current stimulation on motor sequence learning and upper limb function after stroke

OBJECTIVE: To assess the impact of electrode arrangement on the efficacy of tDCS in stroke survivors and determine whether changes in transcallosal inhibition (TCI) underlie improvements. METHODS: 24 stroke survivors (3-124months post-stroke) with upper limb impairment participated. They received blinded tDCS during a motor sequence learning task, requiring the paretic arm to direct a cursor to illuminating targets on a monitor. Four tDCS conditions were studied (crossover); anodal to ipsilesional M1, cathodal to contralesional M1, bihemispheric, sham. The Jebsen Taylor hand function test (JTT) was assessed pre- and post-stimulation and TCI assessed as the ipsilateral silent period (iSP) duration using transcranial magnetic stimulation. RESULTS: The time to react to target illumination reduced with learning of the movement sequence, irrespective of tDCS condition (p>0.1). JTT performance improved after unilateral tDCS (anodal or cathodal) compared with sham (p0.1). There was no effect of tDCS on change in iSP duration (p>0.1). CONCLUSIONS: Unilateral tDCS is effective for improving JTT performance, but not motor sequence learning. SIGNIFICANCE: This has implications for the design of future clinical trials

Cerebrovascular manifestations of herpes simplex virus infection of the central nervous system: a systematic review

Abstract Background Intracerebral hemorrhage and ischemic stroke are increasingly recognized complications of central nervous system (CNS) infection by herpes simplex virus (HSV). Aim of the study To analyze clinical, imaging, and laboratory findings and outcomes of cerebrovascular manifestations of HSV infection. Methods Systematic literature review from January 2000 to July 2018. Results We identified 38 patients (median age 45 years, range 1–73) comprising 27 cases of intracerebral hemorrhage, 10 of ischemic stroke, and 1 with cerebral venous sinus thrombosis. Intracerebral hemorrhage was predominantly (89%) a complication of HSV encephalitis located in the temporal lobe. Hematoma was present on the first brain imaging in 32%, and hematoma evacuation was performed in 30% of these cases. Infarction was frequently multifocal, and at times preceded by hemorrhage (20%). Both a stroke-like presentation and presence of HSV encephalitis in a typical location were rare (25% and 10%, respectively). There was evidence of cerebral vasculitis in 63%, which was exclusively located in large-sized vessels. Overall mortality was 21% for hemorrhage and 0% for infarction. HSV-1 was a major cause of hemorrhagic complications, whereas HSV-2 was the most prevalent agent in the ischemic manifestations. Conclusion We found a distinct pathogenesis, cause, and outcome for HSV-related cerebral hemorrhage and infarction. Vessel disruption within a temporal lobe lesion caused by HSV-1 is the presumed mechanism for hemorrhage, which may potentially have a fatal outcome. Brain ischemia is mostly related to multifocal cerebral large vessel vasculitis associated with HSV-2, where the outcome is more favorable

Endovascular Therapy for Tandem Occlusion in Acute Ischemic Stroke: Intravenous Thrombolysis Improves Outcomes

Ischemic stroke related to tandem internal carotid and middle cerebral artery (TIM) occlusion is a challenging condition where endovascular treatment (EVT) is an emerging revascularization option. The identification of factors influencing clinical outcomes can assist in creating appropriate therapeutic algorithms for such patients. This study aimed to evaluate prognostic factors in the context of EVT for TIM occlusion. We performed a retrospective study of consecutive patients with TIM occlusion admitted within 6 h from symptom onset to two tertiary stroke centers. We recorded the etiology of stroke, clinical deficits at stroke onset and discharge, details of EVT, final infarct volume (FIV), in-hospital mortality, and outcome at three months. Among 73 patients with TIM occlusion, 53 were treated with EVT. The median age was 75.9 years (interquartile range (IQR) 64.6⁻82.6), with the most common etiology of cardioembolism (51.9%). Intravenous thrombolysis with tissue-plasminogen activator (t-PA) was performed in the majority (69.8%) of cases. EVT achieved successful recanalization with a thrombolysis in cerebral infarction (TICI) grade of 2b or 3 in 67.9%. A good outcome (modified Rankin score of 0⁻2 at three months) was observed in 37.7%. After adjustment for age, the National Institutes of Health Stroke Scale (NIHSS) at admission, and success of recanalization, smaller final infarct volume (odds ratio (OR) 0.021 for FIV above 25th percentile (95% CI 0.001⁻0.332, p = 0.005)) and administration of intravenous t-PA (OR 12.04 (95% CI 1.004⁻144.392, p = 0.049)) were associated with a good outcome at three months. Our study demonstrates that bridging with t-PA is associated with improved outcomes in the setting of tandem ICA and MCA occlusions treated with EVT and should therefore not be withheld in eligible patients