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Magnetization transfer ratio (MTR) and brain volumetric imaging are (semi-)quantitative MRI markers capturing demyelination, axonal degeneration and/or inflammation. However, factors shaping variation in these traits are largely unknown. In this study, we collected a longitudinal cohort of 33 multiple sclerosis (MS) patients and extended it cross-sectionally to 213. We measured MTR in lesions, normal-appearing white matter (NAWM), normal-appearing grey matter (NAGM) and total brain, grey matter, white matter and lesion volume. We also calculated the polygenic MS risk score. Longitudinally, inter-patient differences at inclusion and intra-patient changes during follow-up together explained > 70% of variance in MRI, with inter-patient differences at inclusion being the predominant source of variance. Cross-sectionally, we observed a moderate correlation of MTR between NAGM and NAWM and, less pronounced, with lesions. Age and gender explained about 30% of variance in total brain and grey matter volume. However, they contributed less than 10% to variance in MTR measures. There were no significant associations between MRI traits and the genetic risk score. In conclusion, (semi-)quantitative MRI traits change with ongoing disease activity but this change is modest in comparison to pre-existing inter-patient differences. These traits reflect individual variation in biological processes, which appear different from those involved in genetic MS susceptibility.

Introduction: Microhemorrhages have not been described in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome (MELAS) on magnetic resonce imaging (MRI). Main symptoms and/or important findings: A MELAS-patient had a rapid succession of 3 stroke-like episodes with dysphasia, visual field deficits and paresis of the right arm. MRI showed a lesion with corticosubcortical vasogenic edema without reduced diffusion, conforming to a stroke-like MELAS-lesion. Microhemorrhages within MELAS-lesions were detected on MRI. The main diagnoses, therapeutic interventions, and outcomes: Microhemorrhages are an atypical imaging finding in MELAS. The patient was treated with L-arginine.Conclusion: Microhemorrhages can present on MRI in (sub)acute MELAS lesions and may reflect mitochondrial microangiopathy.

PurposeDetection of intracranial arterial occlusions on CT angiography (CTA) can be challenging. We studied the value of CT perfusion (CTP) for arterial occlusion detection in the anterior circulation amongst radiologists and neurologists, both experienced and less experienced.MethodsSeven raters reviewed CTAs of 335 acute stroke patients with and without occlusions. We evaluated occlusion detection with and without CTP. We categorized the occlusions by location. Two experienced raters exposed to all baseline and follow-up imaging defined a consensus gold standard. We calculated sensitivity, specificity and accuracy for occlusion detection with and without CTP and compared the area under the curve (AUC). We also compared the performance of radiologists versus neurologists and of experienced and less experienced raters.ResultsWe included 260 patients with ≥1 occlusion and 75 without occlusions. The accuracy of occlusion detection was greater with CTP assistance compared to CTA only (AUC 0.93 vs 0.91, p= 0.03 for proximal and AUC 0.88 vs 0.81, p<0.001 for distal). Distal occlusion detection accuracy improved with CTP in neurologists and in radiologists, whereas improved proximal occlusion detection accuracy was only present in neurologists. Adding CTP improved distal occlusion detection in experienced and less experienced raters. Proximal occlusion detection accuracy improved with CTP in experienced raters, and trended towards improvement in less experienced raters.ConclusionAssistance of CTP maps may improve the accuracy of intracranial occlusion detection on CTA. In this study, the benefit was most profound for distal occlusions, regardless of experience level or specialty background of the rater.

Background and purpose Guidelines help physicians to provide optimal care for stroke patients, but implementation is challenging due to the quantity of recommendations. Therefore a practical overview related to applicability of recommendations can be of assistance. Methods A systematic review was performed on ischaemic stroke guidelines published in scientific journals, covering the whole acute care process for patients with ischaemic stroke. After data extraction, experts rated the recommendations on dimensions of applicability, that is, actionability, feasibility and validity, on a 9‐point Likert scale. Agreement was defined as a score of ≥8 by ≥80% of the experts. Results Eighteen articles were identified and 48 recommendations were ultimately extracted. Papers were included only if they described the whole acute care process for patients with ischaemic stroke. Data extraction and analysis revealed variation in terms of both content and comprehensiveness of this description. Experts reached agreement on 34 of 48 (70.8%) recommendations in the dimension actionability, for 16 (33.3%) in feasibility and for 15 (31.3%) in validity. Agreement on all three dimensions was reached for seven (14.6%) recommendations: use of a stroke unit, exclusion of intracerebral haemorrhage as differential diagnosis, administration of intravenous thrombolysis, performance of electrocardiography/cardiac evaluation, non‐invasive vascular examination, deep venous thrombosis prophylaxis and administration of statins if needed. Discussion and conclusion Substantial variation in agreement was revealed on the three dimensions of the applicability of recommendations. This overview can guide stroke physicians in improving the care process and removing barriers where implementation may be hampered by validity and feasibility.

Background We previously validated simplified electroencephalogram (EEG) tracings obtained by a bispectral index (BIS) device against standard EEG. This retrospective study now investigated whether BIS EEG tracings can predict neurological outcome after cardiac arrest (CA). Methods Bilateral BIS monitoring (BIS VISTA™, Aspect Medical Systems, Inc. Norwood, USA) was started following intensive care unit admission. Six, 12, 18, 24, 36 and 48 h after targeted temperature management (TTM) at 33 °C was started, BIS EEG tracings were extracted and reviewed by two neurophysiologists for the presence of slow diffuse rhythm, burst suppression, cerebral inactivity and epileptic activity (defined as continuous, monomorphic, > 2 Hz generalized sharp activity or continuous, monomorphic, < 2 Hz generalized blunt activity). At 180 days post-CA, neurological outcome was determined using cerebral performance category (CPC) classification (CPC1-2: good and CPC3-5: poor neurological outcome). Results Sixty-three out-of-hospital cardiac arrest patients were enrolled for data analysis of whom 32 had a good and 31 a poor neurological outcome. Epileptic activity within 6–12 h predicted CPC3-5 with a positive predictive value (PPV) of 100%. Epileptic activity within time frames 18–24 and 36–48 h showed a PPV for CPC3-5 of 90 and 93%, respectively. Cerebral inactivity within 6–12 h predicted CPC3-5 with a PPV of 57%. In contrast, cerebral inactivity between 36 and 48 h predicted CPC3-5 with a PPV of 100%. The pattern with the worst predictive power at any time point was burst suppression with PPV of 44, 57 and 40% at 6–12 h, at 18–24 h and at 36–48 h, respectively. Slow diffuse rhythms at 6–12 h, at 18–24 h and at 36–48 h predicted CPC1-2 with PPV of 74, 76 and 80%, respectively. Conclusion Based on simplified BIS EEG, the presence of epileptic activity at any time and cerebral inactivity after the end of TTM may assist poor outcome prognostication in successfully resuscitated CA patients. A slow diffuse rhythm at any time after CA was indicative for a good neurological outcome.

Aims Penumbral selection is best‐evidence practice for thrombectomy in the 6‐24 hour window. Moreover, it helps to identify the best responders to thrombolysis. Multimodal computed tomography (mCT) at the primary centre—including noncontrast CT, CT perfusion, and CT angiography—may enhance reperfusion therapy decision‐making. We developed a network with five spoke primary stroke sites and assessed safety, feasibility, and influence of mCT in rural hospitals on decision‐making for thrombolysis. Methods Consecutive patients assessed via telemedicine from April 2013 to June 2018. Clinical outcomes were measured, and decision‐making compared using theoretical models for reperfusion therapy applied without mCT guidance. Symptomatic intracranial hemorrhage (sICH) was assessed according to Safe Implementation of Treatments in Stroke Thrombolysis Registry criteria. Results A total of 334 patients were assessed, 240 received mCT, 58 were thrombolysed (24.2%). The mean age of thrombolysed patients was 70 years, median baseline National Institutes of Health Stroke Scale was 10 (IQR 7‐18) and 23 (39.7%) had a large vessel occlusion. 1.7% had sICH and 3.5% parenchymal hematoma. Three months poststroke, 55% were independent, compared with 70% in the non‐thrombolysed group. Conclusion Implementation of CTP in rural centers was feasible and led to high thrombolysis rates with low rates of sICH.

Introduction: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0–5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings. Patients and methods: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6–24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions. Results: Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0–5 (n = 310), receiving EVT (n = 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3–6 vs 6 IQR 4–6; aOR 0.4, 95% CI 0.2–0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2–18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2–0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6–10 in the extended time window (interaction aOR 0.9; 95% CI 0.5–1.7). Conclusion: In the extended time window, patients with ASPECTS 0–5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6–10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window. Trial registration number: clinicaltrials.gov; Unique identifier: NCT04096248

Introduction Whether the risk-benefit profile of once-daily versus twice-daily direct oral anticoagulants (DOAC) differs after atrial fibrillation(AF)-associated ischemic stroke is unclear. We explored this in a post-hoc analysis of ELAN trial data (NCT03148457). Patients and methods We compared the risk of the primary outcome (recurrent ischemic stroke, systemic embolism, intracranial hemorrhage (ICH), major extracranial bleeding, vascular death) from treatment initiation to the trial’s 90-day follow-up in participants treated with once-daily or twice-daily DOAC after AF-associated stroke using Firth’s logistic and Cox proportional hazards regression in unadjusted, inverse-probability-of-treatment-weighted and augmented-inverse-probability-weighted models to address confounding. Secondary outcomes were the primary outcome components and non-major bleeding. We calculated the net clinical benefit (NCB) of twice-daily over once-daily DOAC by subtracting the weighted rate of excess bleeding attributable to twice-daily DOAC from the rate of excess ischemic events possibly prevented by twice-daily DOAC. Results We analyzed 1890/2013 (94%) participants (median age 77 years, 45% female), of whom 384 (20%) received once-daily and 1506 (80%) twice-daily DOAC. The primary outcome occurred in 64 (3.4%) participants, and did not differ between DOAC types in logistic (ORunadjusted 0.89 (95% CI 0.50–1.66); ORweighted 1.34 (0.71–2.79); ORaugmented 1.45 (0.81–3.21); twice-daily vs once-daily DOAC) nor in Cox models. We identified no clear differences in any secondary outcome. NCB analysis revealed a near-neutral net effect of twice-daily versus once-daily DOAC (+0.28 to +0.67 weighted events possibly prevented/100 person-months for ICH weights 1.5–3.3). Discussion and conclusion The risk-benefit profile of once-daily versus twice-daily DOAC after AF-associated ischemic stroke does not seem to differ.

Background The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window. Methods We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists. The non-interventionist group was defined by all other specialties of the respondents: stroke neurologist, neuroradiologist, emergency medicine physician, trainee (fellows and residents) and others. Results Of 3000 invited to participate, 1506 (1027 non-interventionists, 478 interventionists, 1 declined to specify) physicians completed the study. Interventionist respondents were more likely to proceed directly to EVT (39.5% vs. 19.5%; p  < 0.0001) compared to non-interventionist respondents in patients with favorable ASPECTS (Alberta Stroke Program Early CT Score). Despite no difference in access to advanced imaging, interventionists were more likely to prefer CT/CTA alone (34.8% vs. 21.0%) and less likely to prefer CT/CTA/CTP (39.1% vs. 52.4%) for patient selection ( p  < 0.0001). When faced with uncertainty, non-interventionists were more likely to follow clinical guidelines (45.1% vs. 30.2%) while interventionists were more likely to follow their assessment of evidence (38.7% vs. 27.0%) ( p  < 0.0001). Conclusion Interventionists were less likely to use advanced imaging techniques in selecting LVO patients presenting in the late window and more likely to base their decisions on their assessment of evidence rather than published guidelines. These results reflect gaps between interventionists and non-interventionists reliance on clinical guidelines, the limits of available evidence, and clinician belief in the utility of advanced imaging.