Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with ...cervical artery dissection, although some current guidelines—based on available evidence from mostly observational studies—suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection.
We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio INR 2·0–3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460.
Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% 95% CI −4 to 21, non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group.
Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection.
Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.
Objective
We present a systematic review of the literature regarding types and anatomic distribution of fractures in association with generalized convulsive status epilepticus (GCSE) and convulsive ...seizures in adult patients accompanied by an illustrative case of a patient with GCSE and diffuse postictal pain from underlying bone fractures.
Methods
The library search engines PubMed and EMBASE were screened systematically using predefined search terms. All identified articles written in English were screened for eligibility by two reviewers. The preferred reporting items for systematic reviews and meta‐analyses guidelines were followed.
Results
The screening of 3145 articles revealed 39 articles meeting the inclusion criteria. Among all fractures, bilateral posterior fracture‐dislocations of the shoulders were reported most frequently (33%), followed by thoracic and lumbar vertebral compression fractures (29%), skull and jaw fractures (8%), and bilateral femoral neck fractures (6%). Risk factors for seizure‐related fractures are seizure severity, duration of epilepsy, the use of antiseizure drugs known to decrease bone density, and a family history of fractures. Based on these findings, a three‐step screening procedure is proposed to uncover fractures in the postictal state. All studies were retrospective without standardized screening methods for seizure‐associated fractures resulting in a very low level of evidence and a high risk of bias.
Significance
Posterior fracture‐dislocations of the shoulders, thoracic and lumbar vertebral compression, fractures of the skull and jaw, and bilateral femoral neck fractures are most frequently reported. Preventive measures including bone densitometry, calcium/vitamin D supplementation, and bisphosphonate therapy should be reinforced in epilepsy patients at risk of osteoporosis. As long as the effect of standardized screening of fractures is not investigated, it is too early to integrate such a screening into treatment guidelines. In the meantime, clinicians are urged to heighten awareness regarding seizure‐associated fractures, especially in patients with postictal pain, as symptoms can be unspecific and misinterpretation may impede rehabilitation.
Six randomized controlled clinical trials have assessed whether mechanical thrombectomy (MT) alone is non-inferior to intravenous thrombolysis (IVT) plus MT within 4.5 hours of symptom onset in ...patients with anterior circulation large vessel occlusion (LVO) ischemic stroke and no contraindication to IVT. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted with the European Society of Minimally Invasive Neurological Therapy (ESMINT) according to ESO standard operating procedure based on the GRADE system. We identified two relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert opinion was provided if insufficient evidence was available to provide recommendations based on the GRADE approach.For stroke patients with anterior circulation LVO directly admitted to a MT-capable center ('mothership') within 4.5 hours of symptom onset and eligible for both treatments, we recommend IVT plus MT over MT alone (moderate evidence, strong recommendation). MT should not prevent the initiation of IVT, nor should IVT delay MT. In stroke patients with anterior circulation LVO admitted to a center without MT facilities and eligible for IVT ≤4.5 hours and MT, we recommend IVT followed by rapid transfer to a MT capable-center ('drip-and-ship') in preference to omitting IVT (low evidence, strong recommendation). Expert consensus statements on ischemic stroke on awakening from sleep are also provided. Patients with anterior circulation LVO stroke should receive IVT in addition to MT if they have no contraindications to either treatment.
Objective
Classical clinical characteristics associated with successful or unsuccessful extubation are unreliable in neurocritically ill patients, and attempts to predict successful extubation in ...this context have failed. We aimed to investigate the frequency of mechanical ventilation (MV) in adult patients in status epilepticus (SE) and its clinical associations, to identify predictors at SE onset of prolonged postictal MV, and to determine the associated outcomes with prolonged MV.
Methods
From 2012 to 2018, SE patients treated in intensive care units at a Swiss academic care center were included. Multivariable Poisson regression adjusting for potential confounders, such as continuously administered anesthetics, was performed to identify risks for postictal MV for >24 h after SE and its association with no return to neurologic function and death. Linear regression was performed to identify correlations between the durations of administered specific anesthetics and postictal MV.
Results
Of 262 patients, 42% were ventilated, with 24% being on ventilators for >24 h after SE. Patients with prolonged postictal MV were extubated at a median of 7 days, with 56% not being extubated on the day of successful weaning from MV because of altered consciousness and/or lack of airway‐protective reflexes. After extubation, noninvasive ventilation and reintubation were rarely needed. Prolonged postictal MV was associated with increased risk for death independent of potential confounders, including fatal etiology of SE, age, SE severity, and use of anesthetics (relative risk for every additional day = 2.7, p = .024). At SE onset, decreased consciousness and presumed fatal etiology predicted prolonged postictal MV. Anesthetics were associated with prolonged MV, but linear regression could not identify significant correlations.
Significance
Our data reveal that prolonged postictal MV is frequent and an independent risk factor for death. Extubation is often delayed for days despite sufficient weaning from the ventilator and altered airway‐protective reflexes in only few patients. Studies need to investigate whether more rigorous extubation strategies improve outcome.
Summary Background Identification of patients at highest risk of early stroke after transient ischaemic attack has been improved with imaging based scores. We aimed to compare the validity and ...prognostic utility of imaging-based stroke risk scores in patients after transient ischaemic attack. Methods We did a pooled analysis of published and unpublished individual-patient data from 16 cohort studies of transient ischaemic attack done in Asia, Europe, and the USA, with early brain and vascular imaging and follow up. All patients were assessed by stroke specialists in hospital settings as inpatients, in emergency departments, or in transient ischaemic attack clinics. Inclusion criteria were stroke-specialist confirmed transient ischaemic attack, age of 18 years or older, and MRI done within 7 days of index transient ischaemic attack and before stroke recurrence. Multivariable logistic regression was done to analyse the predictive utility of abnormal diffusion-weighted MRI, carotid stenosis, and transient ischaemic attack within 1 week of index transient ischaemic attack (dual transient ischaemic attack) after adjusting for ABCD2 score. We compared the prognostic utility of the ABCD2, ABCD2-I, and ABCD3-I scores using discrimination, calibration, and risk reclassification. Findings In 2176 patients from 16 cohort studies done between 2005 and 2015, after adjusting for ABCD2 score, positive diffusion-weighted imaging (odds ratio OR 3·8, 95% CI 2·1–7·0), dual transient ischaemic attack (OR 3·3, 95% CI 1·8–5·8), and ipsilateral carotid stenosis (OR 4·7, 95% CI 2·6–8·6) were associated with 7 day stroke after index transient ischaemic attack (p<0·001 for all). 7 day stroke risk increased with increasing ABCD2-I and ABCD3-I scores (both p<0·001). Discrimination to identify early stroke risk was improved for ABCD2-I versus ABCD2 (2 day c statistic 0·74 vs 0·64; p=0·006). However, discrimination was further improved by ABCD3-I compared with ABCD2 (2 day c statistic 0·84 vs 0·64; p<0·001) and ABCD2-I ( c statistic 0·84 vs 0·74; p<0·001). Early stroke risk reclassification was improved by ABCD3-I compared with ABCD2-I score (clinical net reclassification improvement 33% at 2 days). Interpretation Although ABCD2-I and ABCD3-I showed validity, the ABCD3-I score reliably identified highest-risk patients at highest risk of a stroke after transient ischaemic attack with improved risk prediction compared with ABCD2-I. Transient ischaemic attack management guided by ABCD3-I with immediate stroke-specialist assessment, urgent MRI, and vascular imaging should now be considered, with monitoring of safety and cost-effectiveness. Funding Health Research Board of Ireland, Irish Heart Foundation, Irish Health Service Executive, Irish National Lottery, National Medical Research Council of Singapore, Swiss National Science Foundation, Bangerter-Rhyner Foundation, Swiss National Science Foundation, Swisslife Jubiläumsstiftung for Medical Research, Swiss Neurological Society, Fondazione Dr Ettore Balli (Switzerland), Clinical Trial Unit of University of Bern, South Korea's Ministry for Health, Welfare, and Family Affairs, UK Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre.
BACKGROUND:
Endovascular treatment (EVT) for cerebral vein thrombosis (CVT) has not been proven to be more effective than anticoagulation based on recent results of the Thrombolysis or ...Anticoagulation for Cerebral Venous Thrombosis (TO-ACT) randomized clinical trial.
OBJECTIVE:
To compare outcomes of EVT vs medical management in CVT.
METHODS:
We compared EVT vs medical management in a retrospective multinational cohort of consecutive patients with CVT across 4 countries (USA, Italy, Switzerland, and New Zealand) and 27 sites (2015-2020), using propensity score matching (PSM) and inverse probability treatment weighting (IPTW), and meta-analyzed these results with the TO-ACT trial. The primary outcome was excellent functional outcome (modified Rankin Scale mRS 0-1) at 90 days.
RESULTS:
Of the 987 patients, the mean age was 45.7 ± 16.9 years and 79 (8%) underwent EVT. With PSM (n = 124), there were no major differences in clinical or imaging features between groups other than a higher proportion of female patients receiving EVT (81% vs 65%,
P
= .04). There was no difference in the primary outcome with PSM (odds ratio OR 1.48, 95% CI, 0.55-3.96) or IPTW (OR 1.02, 95% CI, 0.34-3.06). EVT was associated with a higher 90-day shift in modified Rankin Scale (OR 2.00, 95% CI, 1.01-3.98) and mortality with IPTW (OR 4.60, 95% CI, 1.10-19.23) but no other differences in secondary outcomes with PSM or IPTW. A meta-analysis of primary and secondary outcomes from TO-ACT and PSM patients from anticoagulation in the treatment of cerebral venous thrombosis also showed no significant association with EVT in primary or secondary outcomes.
CONCLUSION:
In this large observational cohort, there was no evidence of benefit with EVT for CVT. These findings corroborate the results from the TO-ACT trial.
Correction of hyponatremia might represent an additional treatment for improving stroke patients' clinical outcomes.
Admission hyponatremia is associated with worse clinical outcome in stroke ...patients, but whether normalization of hyponatremia improves outcome is unknown. We investigated whether normalization of hyponatremia affects patients' disability, mortality, and stroke recurrence within 3 months; length of hospitalization; and discharge destination.
This was a registry-based analysis of data collected between January 2016 and December 2018. We linked data from Swiss Stroke Registry (SSR) with electronic patients' records for extracting sodium values.
We analyzed data of hospitalized patients treated at University Hospital of Basel.
Stroke patients whose data and informed consent were available.
Modified Rankin Scale (mRS) score at 3 months. The tested hypothesis was formulated after SSR data collection but before linkage with electronic patients' records.
Of 1995 patients, 144 (7.2%) had hyponatremia on admission; 102 (70.8%) reached normonatremia, and 42 (29.2%) remained hyponatremic at discharge. An increase of initial sodium was associated with better functional outcome at 3 months (odds ratio OR 0.94; 95% CI, 0.90-0.99, for a shift to higher mRS per 1 mmol/L sodium increase). Compared with normonatremic patients, patients who remained hyponatremic at discharge had a worse functional outcome at 3 months (odds ratio 2.46; 95% CI, 1.20-5.03, for a shift to higher mRS). No effect was found on mortality, recurrence, or length of hospitalization.
In hospitalized acute stroke patients, persistent hyponatremia is associated with worse functional outcome. Whether active correction of hyponatremia improves outcome remains to be determined in prospective studies.
Venous thromboembolism (VTE) can occur simultaneously with a cryptogenic stroke (CS) linked to patent foramen ovale (PFO), given paradox thromboembolism as potential stroke cause. However, little is ...known on the frequency of concomitant VTE and CS. We aimed to review the literature on the frequency of VTE in patients with CS linked to PFO (primary aim) and of ischemic stroke (IS) among patients with pulmonary embolism (PE) (secondary aim).
We performed a Medline search for cohort studies, written in English, with the following characteristics: (a) enrolling patients hospitalized for an acute ischemic stroke undergoing a work-up for deep venous thrombosis (DVT) and/or PE. To be included in this review, a study had to have at least a subgroup of patients with PFO; (b) the time interval between the index stroke and the work-up had to be within 40 days and the studies had to differentiate between DVT and PE. For the secondary aim, studies had to include patients with acute PE, known PFO-status and routine brain imaging on admission or within 1 year.
We found eight studies reporting on the frequency of VTE after an acute CS linked to PFO. Concerning DVT, the reported frequency ranged between 7 and 27%; concerning PE, it lied between 4.4 and 37%. Six studies assessed the frequency of ischemic brain lesions among patients with an acute PE. In all studies, the presence of PFO was associated with ischemic brain lesions, both at baseline and follow-up.
VTE can be detected in patients with CS linked to PFO. While -based on the presented literature-routine screening for VTE in patients with CS linked to PFO does not appear justified, history taking, and clinical exam should consider concomitant VTE. Whenever clinically suspected, the threshold to trigger ancillary testing for VTE should be low. Among patients with an acute PE and PFO, vigilance for new neurologic deficits should be increased, with a low threshold for brain imaging.
Predicting the duration of poststroke dysphagia is important to guide therapeutic decisions. Guidelines recommend nasogastric tube (NGT) feeding if swallowing impairment persists for 7 days or longer ...and percutaneous endoscopic gastrostomy (PEG) placement if dysphagia does not recover within 30 days, but, to our knowledge, a systematic prediction method does not exist.
To develop and validate a prognostic model predicting swallowing recovery and the need for enteral tube feeding.
We enrolled participants with consecutive admissions for acute ischemic stroke and initially severe dysphagia in a prospective single-center derivation (2011-2014) and a multicenter validation (July 2015-March 2018) cohort study in 5 tertiary stroke referral centers in Switzerland.
Severely impaired oral intake at admission (Functional Oral Intake Scale score <5).
Recovery of oral intake (primary end point, Functional Oral Intake Scale ≥5) or return to prestroke diet (secondary end point) measured 7 (indication for NGT feeding) and 30 (indication for PEG feeding) days after stroke.
In total, 279 participants (131 women 47.0%; median age, 77 years interquartile range, 67-84 years) were enrolled (153 54.8% in the derivation study; 126 45.2% in the validation cohort). Overall, 64% (95% CI, 59-71) participants failed to recover functional oral intake within 7 days and 30% (95% CI, 24-37) within 30 days. Prolonged swallowing recovery was independently associated with poor outcomes after stroke. The final prognostic model, the Predictive Swallowing Score, included 5 variables: age, stroke severity on admission, lesion location, initial risk of aspiration, and initial impairment of oral intake. Predictive Swallowing Score prediction estimates ranged from 5% (score, 0) to 96% (score, 10) for a persistent impairment of oral intake on day 7 and from 2% to 62% on day 30. Model performance in the validation cohort showed a discrimination (C statistic) of 0.84 (95% CI, 0.76-0.91; P < .001) for predicting the recovery of oral intake on day 7 and 0.77 (95% CI, 0.67-0.87; P < .001) on day 30, and a discrimination for a return to prestroke diet of 0.94 (day 7; 95% CI, 0.87-1.00; P < .001) and 0.71 (day 30; 95% CI, 0.61-0.82; P < .001). Calibration plots showed high agreement between the predicted and observed outcomes.
The Predictive Swallowing Score, available as a smartphone application, is an easily applied prognostic instrument that reliably predicts swallowing recovery. It will support decision making for NGT or PEG insertion after ischemic stroke and is a step toward personalized medicine.
The optimal timing to start direct oral anticoagulants (DOACs) after an acute ischaemic stroke (AIS) related to atrial fibrillation (AF) remains unclear. We aimed to compare early (≤5 days of AIS) ...versus late (>5 days of AIS) DOAC-start.
This is an individual patient data pooled analysis of eight prospective European and Japanese cohort studies. We included patients with AIS related to non-valvular AF where a DOAC was started within 30 days. Primary endpoints were 30-day rates of recurrent AIS and ICH.
A total of 2550 patients were included. DOACs were started early in 1362 (53%) patients, late in 1188 (47%). During 212 patient-years, 37 patients had a recurrent AIS (1.5%), 16 (43%) before a DOAC was started; 6 patients (0.2%) had an ICH, all after DOAC-start. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent AIS, while 2 patients (0.1%) had an ICH. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent AIS; 4 patients (0.3%) suffered from ICH. In the propensity score-adjusted comparison of late versus early DOAC-start groups, there was no statistically significant difference in the hazard of recurrent AIS (aHR=1.2, 95% CI 0.5 to 2.9, p=0.69), ICH (aHR=6.0, 95% CI 0.6 to 56.3, p=0.12) or any stroke.
Our results do not corroborate concerns that an early DOAC-start might excessively increase the risk of ICH. The sevenfold higher risk of recurrent AIS than ICH suggests that an early DOAC-start might be reasonable, supporting enrolment into randomised trials comparing an early versus late DOAC-start.
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