Intravenous thrombolysis for ischemic stroke in the posterior circulation: A systematic review and meta-analysis.

OBJECTIVES: Intravenous thrombolysis (IVT) is recommended in patients with ischemic stroke in the anterior and posterior circulation. Neurological outcomes due to posterior circulation strokes (PCS) without treatment remain poor. Our aim was to overview the literature on outcomes of IVT and conservative treatment in PCS, based on a systematic review and meta-analysis. METHODS: A systematic literature search was performed on February 27th 2023. Outcome measures included favorable functional outcome at 90 days (modified Rankin Scale [mRS] 0-2), mortality at 90 days, and symptomatic intracranial hemorrhages (sICH). Weighted averages with DerSimonian-Laird approach was used to analyze the data. Subgroup analyses by time window were performed: standard time window (<4.5 hours after symptom onset) and extended time window (>4.5 hours). Analyses were performed using R. RESULTS: Eight prospective and four retrospective cohort studies were included (n = 1589 patients); no studies with conservative treatment were eligible. The pooled weighted probability regarding favorable functional outcome after IVT was 63 % (95 %CI:0.45-0.78), for mortality 19 % (95 %CI:0.11-0.30), and for sICH 4 % (95 %CI:0.02-0.07). Subgroup analyses showed higher probabilities on achieving favorable functional outcomes for patients treated in the standard (77 %; 95 %CI:0.62-0.88) compared to the extended time window (38 %; 95 %CI:0.29-0.48) with RR = 1.93 (95 %CI:1.66-2.24). Lower probabilities regarding mortality at 90 days and sICH were seen in patients treated in standard compared to extended time window (RR = 0.42, 95 %CI:0.34-0.51 and RR = 0.27, 95 %CI:0.16-0.45, respectively). CONCLUSIONS: IVT in patients with PCS seems to be safe and effective in standard and extended time window. The effect of IVT is higher in the standard time window.

Standard operating procedure for idarucizumab reversal of dabigatran anticoagulation in ischemic and hemorrhagic stroke.

BACKGROUND: Reversal of dabigatran anticoagulation activity using idarucizumab is indicated for individuals suffering from life-threatening or non-controlled bleeding and those in need of urgent operation or invasive intervention. Through idarucizumab application patients with acute ischemic stroke (AIS) may regain eligibility for intravenous thrombolysis (IVT) and patients with intracranial hemorrhage (ICH) may show less hematoma growth, thereby improving functional outcome in both groups. However, evidence is limited, and international guidelines contain heterogenous recommendations substantiating the need for the review of evidence and standard operating procedures (SOPs). MATERIALS AND METHODS: For our review, we searched PubMed for all published articles using idarucizumab and ischemic stroke/hemorrhagic stroke as keywords. Illustrating two clinical cases, we discuss the current literature and national guidelines. RESULTS: Our search retrieved 47 articles of which 8 case studies or series made public after 2020/2021, 28 reviews, 1 leading opinion article, 1 editorial and 10 guidelines. Summarizing the available evidence, idarucizumab application in stroke patients taking dabigatran results in decreased mortality rate and improved functional outcomes. Based on two clinical cases from our departments, we provide SOPs on how to deal with eligible patients in a time-efficient way, thereby reducing door-to-needle times in AIS and preventing early deterioration in ICH patients. CONCLUSION: Reversal of dabigatran with idarucizumab in stroke patients appears easy to manage, safe and beneficial. The SOPs aim to reassure stroke physicians to include dabigatran reversal into their daily clinical routine when dealing with patients presenting with ischemic or hemorrhagic stroke under dabigatran therapy.

Direct oral anticoagulants for secondary stroke prevention in patients over 80 years of age: the role of geriatric functional status.

Prescribing anticoagulation therapy in very old (≥ 80-years) patients with atrial fibrillation (AF) is an emerging clinical issue, but current knowledge and recommendations are insufficient. We aimed to determine the efficacy and safety of direct oral anticoagulants (DOACs) in secondary stroke prevention in very old patients and to explore the related geriatric functional status of these patients. Three hundred fifty-three consecutive ≥ 80-year-old patients treated for transient ischemic attack (TIA) or ischemic stroke (IS) at the neurological clinic at UMC Ljubljana, who were prescribed DOACs for AF between December 2012 and May 2020, were included. Data regarding recurrent TIA/IS, major bleeds, intracranial hemorrhage (ICH) and death were collected. Data were descriptively compared with data from RCTs- including younger patients. Patients prescribed DOACs between January 2018 and May 2020 were contacted in December 2020, and their functional status was assessed using the Barthel index (BI). The efficacy of secondary stroke prevention with DOACs was comparable to RCTs for significantly younger patients. Major bleeds occurred more often, but most incidences were gastrointestinal, and the rate of ICH was comparable. Importantly, most patients were highly independent determined by BI. Overall, our real world results suggest that DOACs are as effective at preventing IS in secondary prevention in very old patients than in younger patients and that geriatric functional assessment could be a useful tool in the decision-making process.

Preceding Head Trauma in Four Cases of Sporadic Cerebral Amyloid Angiopathy - Case Report Series.

BACKGROUND: CAA is a heterogeneous group of diseases caused by Aß deposition in the vascular walls, often leading to lobar ICH and cognitive impairment. Although CAA is rare in younger patients, it has been associated with specific mutations as well as with other causes. CASE PRESENTATION: We present four cases of patients with CAA and recurrent ICH who have a history of severe TBI in childhood. CONCLUSION: Our cases as well as review of the literature suggest that a history of TBI in patients with genetic predispositions such as male sex may be associated with CAA in young persons.

Revascularization outcomes following acute ischemic stroke in patients taking direct oral anticoagulants: a single hospital cohort study.

Successful revascularization therapy is of paramount importance in patients suffering acute ischemic stroke (AIS). However, there is currently only limited evidence on revascularization outcomes for patients suffering AIS while treated with direct oral anticoagulants (DOACs). The aim of our study was to determine the efficacy and safety of intravenous thrombolysis (IVT) and mechanical reperfusion (MeR) in AIS patients taking DOACs, and compare them to randomized clinical trials (RCTs), which included patients without DOAC treatment. In an observational cohort study, we analyzed clinical and radiological outcomes following AIS for all consecutive patients on DOAC therapy treated by IVT or MeR, between 2013 and 2019, at the University Medical Center Ljubljana. Patients in the IVT group were on dabigatran treatment and have received idarucizumab as a reversal agent prior to IVT. Patients in the MeR group had a large vessel occlusion. The primary outcome of the study was efficiency, defined as significant improvement after recanalization (National Institutes of Health Stroke Scale (NIHSS) score improvement of ≥8 points after 24 h and modified Rankin Scale (mRS) ≤2 after 3 months) and safety, defined as occurrence of symptomatic intracerebral hemorrhage (SICH) and mortality. Fifty-one DOAC-treated patients with AIS were included. Nineteen dabigatran-treated patients received IVT after reversal by idarucizumab. Thirty-two patients with a large vessel occlusion (12 on dabigatran, 12 on rivaroxaban, and 8 on apixaban) received MeR. Median NIHSS at admission was 9 in the IVT group and 17 in the MeR group. A significant clinical improvement, 24 h after revascularization (median improvement of NIHSS ≥8), occurred in 84% of patients treated with IVT and 25% of patients treated with MeR. A favorable functional outcome after 3 months (modified Rankin Scale (mRS) ≤2) occurred in 84 % of patients treated with IVT and 44% of patients treated with MeR. SICH occurred in one patient (5%) in the IVT group, and in two patients (6%) in the MeR group. In summary, in our observational study of DOAC-treated AIS patients, the level of IVT efficiency was substantially better than in the RCTs. At the same time, the results of MeR treatment were on the same level as in non-DOAC AIS patients included in the RCTs. The observed safety of IVT and MeR treatment was similar to the RCTs. We propose that thrombi in patients on dabigatran may have increased susceptibility to IVT, thereby allowing for better clinical results.

Re-initiation of anticoagulation after central nervous system hemorrhage during treatment with direct oral anticoagulants: a single hospital cohort study.

BACKGROUND: Central nervous system (CNS) hemorrhage is a serious complication related to direct oral anticoagulant (DOAC) therapy. Current recommendations about re-initiation of anticoagulation treatment are limited to expert opinions. For this purpose, we analyzed the data of all consecutive DOAC patients with CNS hemorrhage, in whom DOACs were reinitiated. METHODS: Over a 6-year period (2012-2018), all consecutive patients with CNS hemorrhage (subdural, subarachnoid, intracerebral, spinal), while receiving DOACs, were included in this observational single-center cohort study. DOAC therapy was reinitiated only in patients with well-controlled arterial hypertension and diabetes, as well as exclusion of vascular malformations and cerebral amyloid angiopathy. The composite primary endpoint comprised of recurrent CNS hemorrhage, ischemic stroke, and mortality; secondary endpoints were separate aforementioned outcomes. RESULTS: Of the 54 patients included, 18 died within a month of CNS hemorrhage. The average observational time was 590 days. DOACs were reinitiated in 13/36 patients (36%); of these patients, three died: none due to ischemic stroke or recurrent CNS bleeding. In 23 patients, anticoagulation was not reinitiated; of these patients, 10 died: three from recurrent CNS hemorrhage, one due to ischemic stroke, and six from causes unrelated to stroke. CONCLUSIONS: In carefully selected patients, re-initiation of DOAC therapy did not increase the rate of both endpoints. Recommendations for DOAC re-initiation, which include hypertension and diabetes control, as well as treated vascular malformations, and excluded cerebral amyloid angiopathy, appear to be valid in clinical practice.

Safety and Outcomes of Intravenous Thrombolysis in Posterior Versus Anterior Circulation Stroke: Results From the Safe Implementation of Treatments in Stroke Registry and Meta-Analysis.

Background and Purpose- Posterior circulation stroke (PCS) accounts for 5% to 19% of patients with acute stroke receiving intravenous thrombolysis. We aimed to compare safety and outcomes following intravenous thrombolysis between patients with PCS and anterior circulation stroke (ACS) and incorporate the results in a meta-analysis. Methods- We included patients in the Safe Implementation of Treatments in Stroke Thrombolysis Registry 2013 to 2017 with computed tomography/magnetic resonance angiographic occlusion data. Outcomes were parenchymal hematoma, symptomatic intracerebral hemorrhage (SICH) per SITS-MOST (Safe Implementation of Thrombolysis in Stroke Monitoring Study), ECASS II (Second European Co-operative Stroke Study) and NINDS (Neurological Disorders and Stroke definition), 3-month modified Rankin Scale score, and death. Adjustment for SICH risk factors (age, sex, National Institutes of Health Stroke Scale, blood pressure, glucose, and atrial fibrillation) and center was done using inverse probability treatment weighting, after which an average treatment effect (ATE) was calculated. Meta-analysis of 13 studies comparing outcomes in PCS versus ACS after intravenous thrombolysis was conducted. Results- Of 5146 patients, 753 had PCS (14.6%). Patients with PCS had lower median National Institutes of Health Stroke Scale: 7 (interquartile range, 4-13) versus 13 (7-18), P<0.001 and fewer cerebrovascular risk factors. In patients with PCS versus ACS, parenchymal hematoma occurred in 3.2% versus 7.9%, ATE (95% CI): -4.7% (-6.3% to 3.0%); SICH SITS-MOST in 0.6% versus 1.9%, ATE: -1.4% (-2.2% to -0.7%); SICH NINDS in 3.1% versus 7.8%, ATE: -3.0% (-6.3% to 0.3%); SICH ECASS II in 1.8% versus 5.4%, ATE: -2.3% (-5.3% to 0.7%). In PCS versus ACS, 3-month outcomes (70% data availability) were death 18.5% versus 20.5%, ATE: 6.0% (0.7%-11.4%); modified Rankin Scale score 0-1, 45.2% versus 37.5%, ATE: 1.7% (-6.6% to 3.2%); modified Rankin Scale score 0-2, 61.3% versus 49.4%, ATE: 2.4% (3.1%-7.9%). Meta-analysis showed relative risk for SICH in PCS versus ACS being 0.49 (95% CI, 0.32-0.75). Conclusions- The risk of bleeding complications after intravenous thrombolysis in PCS was half that of ACS, with similar functional outcomes and higher risk of death, acknowledging limitations of the National Institutes of Health Stroke Scale for stroke severity or infarct size adjustment.

Idarucizumab for dabigatran reversal in daily clinical practice: A case series.

BACKGROUND: Real-life experience with idarucizumab, which reverses the anticoagulant effect of dabigatran, is currently limited. OBJECTIVE: To evaluate efficacy and safety of the clinical use of idarucizumab after its availability in Slovenia. METHODS: We analysed consecutive cases treated with idarucizumab in Slovenia from January to October 2016. The decision to reverse dabigatran with idarucizumab was made by the treating clinicians, as was the assessment of clinical outcomes and blood sampling/monitoring (activated partial thromboplastin time, thrombin time and diluted thrombin time) before and after use. RESULTS: Idarucizumab was used in 17 cases. One patient was treated with the antidote twice with an interval of 2 months between treatments. The indications for idarucizumab use were: emergency surgery (4/17), severe bleeding (11/17; seven with intracranial bleeding) and ischaemic stroke (2/17). During surgery, no excessive bleeding was reported. Five patients died due to cardiogenic, haemorrhagic or septic shock, intracranial bleeding or multiple organ failure. Among cases with laboratory data available, baseline coagulation tests were prolonged in 12/13 cases with bleeding or emergency surgery. After idarucizumab administration, normal coagulation parameters were confirmed in 10/11. However, re-occurrence of dabigatran effect was noted later in four patients with creatinine clearance less than 30 ml min, and one patient with persistent bleeding required retreatment with idarucizumab. CONCLUSION: Our first experiences with idarucizumab use in daily-care settings support a rapid and efficient decrease in the anticoagulant effect of dabigatran in emergency situations. Late re-occurrence of dabigatran effect was noted in a subset of patients with severe renal failure.

Intravenous Thrombolysis After Idarucizumab Application in Acute Stroke Patients-A Potentially Increased Sensitivity of Thrombi to Lysis?

BACKGROUND: Rapid inactivation of dabigatran by its specific inhibitor idarucizamab allows intravenous thrombolysis (IVT) in patients suffering ischemic stroke while being treated with dabigatran. Only limited data of this approach is available and numerous questions regarding efficacy/safety remain to be answered. Herein, we present the findings from the Slovenian national cohort study. METHODS: Retrospective analysis of all stroke patients treated with idarucizumab and IVT (n = 11) in the period from July 2016 to February 2018 from Slovenian region were analyzed. RESULTS: The indication for dabigatran treatment in all 11 cases was nonvalvular atrial fibrillation. Importantly, 6 out of 11 cases were classified as severe ischemic strokes (National Institutes of Health Stroke Scale; NIHSS ≥ 10) with a median NIHSS 13. At admission, prolonged activated partial thromboplastin time was present in 9 patients indicating therapeutic anticoagulation activity. The average door-to-needle time was 156 minutes. After 3 months, 9 patients had a modified Rankin Score of less than or equal to 2 and 7 patients had mRS less than 1 whereas, 2 patients died due to symptomatic intracranial hemorrhage (sICH); 1 due to spontaneous sICH, and the other due to a large ischemic stroke with hemorrhagic transformation. No thrombotic complications were observed. CONCLUSIONS: Our data show that IVT after idarucizumab administration is a safe and effective method of treatment in ischemic stroke patients on dabigatran. We recorded a higher proportion of patients with favorable outcome as well as with sICH compared to the randomized controlled studies which could suggest a higher sensitivity of thrombi to IVT in dabigatran treated patients.

Andexanet Alfa: What We Have Learned from Clinical Trials and Real-World Data.

Andexanet alfa is a specific reversal agent for factor Xa inhibitors with immediate reversal of their anticoagulant effect. Andexanet alfa is currently approved for use in patients treated with rivaroxaban and apixaban who have life-threatening or uncontrolled bleeding. New data from both controlled clinical trials and real-world experience are continuously being published, providing greater insight into the clinical characteristics of the drug, such as efficacy and safety. It is worth considering that andexanet alfa could be of benefit in a variety of different clinical scenarios where patients receiving treatment with apixaban and rivaroxaban (and endoxaban) have life-threatening conditions. These different clinical scenarios, which range from pre-treatment of urgent surgery, especially neurosurgical interventions, and concomitant use of andexanet alfa and prothrombin complex concentrate to onset of bleeding more than 6 h prior to admission, should be clarified as well as the issue of "low/high" dose of andexanet alfa and the need for baseline anti-Xa inhibitor levels measured by point-of-care testing. Finally, management of patients at high risk of thrombosis or recent arterial/venous thrombotic events needs to be further explored. In this current opinion, we address these urgent questions in the light of recent literature and clinical trial data.

Clinical outcomes of reperfusion therapy in patients with site-specific basilar artery occlusion.

BACKGROUND: Despite its low incidence, basilar artery occlusion (BAO) remains a major therapeutic challenge since severe disability and death occur in about 80% of patients. Specific site of BAO (proximal, middle, or distal) has rarely been reported as a prognostic factor in reperfusion therapy. We aimed to explore the relationship between site-specific BAO and clinical outcomes in patients treated with reperfusion therapies. METHODS: We performed a single-centre retrospective study of all consecutive patients with acute BAO admitted to the University Medical Centre Ljubljana between January 2013 and August 2022 who were treated with reperfusion therapies. Patients were grouped according to the location of BAO and compared for baseline characteristics, differences in stroke aetiology, type of reperfusion therapy, success of recanalization, and clinical outcome after 90 days evaluated by the modified Rankin Scale (mRS) score. Statistical analysis was performed with the two-sided ANOVA t-tests for continuous measures, Chi-squared (χ2) tests for categorical measures and a multivariate ordinal logistic regression analysis. RESULTS: The study included 103 patients (47% females, median age 74 years; confidence interval (CI) 72 to 98). Proximal BAO was found in 13%, middle in 13%, and distal in 74% of patients. Cardioembolic etiology was more common in distal (=0.01), and atherosclerotic etiology in proximal and middle BAO occlusions (P=0.02). While distal BAO was more likely to be recanalized using intravenous thrombolysis (IVT) compared with other sites of occlusion (P=0.05), we found no difference between different occlusion sites and the success of endovascular treatment (EVT). Lower age (odds ratio (OR) 0.89; CI 0.84 to 0.95; P<0.01) and shorter time to intervention (OR 0.71; CI 0.53 to 0.95; P=0.02), regardless of it being IVT or EVT, were predictors of an excellent clinical outcome (mRS 0-2). Distal occlusion (OR 28; CI 2.7 to 300; p<0.01) was a strong predictor of a favorable clinical outcome (mRS 0-3). CONCLUSION: Prompt reperfusion, regardless of it being IVT or EVT, increases the chance of excellent clinical outcomes in patients with acute BAO. Distal BAO is more often associated with a favorable clinical outcome compared with the proximal and middle segments.

Recurrent Intracerebral Haematomas Due to Amyloid Angyopathy after Lyodura Transplantation in Childhood.

The number of published cases of presumed iatrogenic cerebral amyloid angiopathy (iCAA) due to the transmission of amyloid ß during neurosurgery is slowly rising. One of the potential ways of transmission is through a cadaveric dura mater graft (LYODURA) exposure during neurosurgery. This is a case of a 46-year-old female patient with no chronic conditions who presented with recurrent intracerebral haemorrhages (ICHs) without underlying vessel pathology. Four decades prior, the patient had a neurosurgical procedure with documented LYODURA transplantation. Brain biopsy confirmed CAA. This is a rare case of histologically proven iCAA after a documented LYODURA transplantation in childhood. Our case and already published iCAA cases emphasize the need for considering neurosurgery procedure history as important data in patients who present with ICH possibly related to CAA.

Idarucizumab in dabigatran-treated patients with acute stroke: a review and clinical update.

Idarucizumab is an antibody fragment specific for the immediate reversal of dabigatran anticoagulation effects. The use of idarucizumab is approved for dabigatran-treated patients suffering from life-threatening or uncontrolled bleeding and those in need of urgent surgery or invasive procedures. Data from randomized controlled clinical trials and real-world experience provide reassuring evidence about the efficacy and safety of idarucizmab use in patients with acute stroke. In this narrative review, we summarize the available real-world evidence and discuss the relevance and importance of idarucizumab treatment in acute stroke patients in everyday clinical practice. In addition, we also discuss special issues like prothrombin complex concentrate application as an alternative to idarucizumab, its application before endovascular therapy, sensitivity of thrombi to lysis, and necessary laboratory examinations.

Specific Reversal Agents for Direct Oral Anticoagulants in Acute Stroke.

Direct oral anticoagulants (DOACs) changed stroke prevention and decreased the risk of ischemic and hemorrhagic complications in patients on oral anticoagulation (OAC) therapy. The numbers of patients prescribed DOACs has increased rapidly. Availability of specific reversal agents opened new avenues in the prevention and management of DOAC complications. An ideal specific reversal agent for a DOAC in acute stroke is an agent which lacks safety concerns and immediately reverses DOAC anticoagulation activity, thereby enabling effective treatment. Reversal of anticoagulant activity is mandatory in patients with acute ischemic stroke (AIS) before performing therapeutic procedures such as intravenous thrombolysis (IVT) and neurosurgery in intracranial hemorrhage (ICH) in order to improve clinical outcomes. In this manuscript we pursue an interdisciplinary approach in discussing advantages and concerns of specific reversal agents in acute stroke DOAC-treated patients in everyday clinical practice.

How much of the variance in functional outcome related to intracerebral hemorrhage volume is already apparent in neurological status at admission?

BACKGROUND: Hematoma volume is a major pathophysiological hallmark of acute intracerebral hemorrhage (ICH). We investigated how the variance in functional outcome induced by the ICH volume is explained by neurological deficits at admission using a mediation model. METHODS: Patients with acute ICH treated in three tertiary stroke centers between January 2010 and April 2019 were retrospectively analyzed. Mediation analysis was performed to investigate the effect of ICH volume (0.8 ml (5% quantile) versus 130.6 ml (95% quantile)) on the risk of unfavorable functional outcome at discharge defined as modified Rankin Score (mRS) ≥ 3 with mediation through National Institutes of Health Stroke Scale (NIHSS) at admission. Multivariable regression was conducted to identify factors related to neurological improvement and deterioration. RESULTS: Three hundred thirty-eight patients were analyzed. One hundred twenty-one patients (36%) achieved mRS ≤ 3 at discharge. Mediation analysis showed that NIHSS on admission explained 30% [13%; 58%] of the ICH volume-induced variance in functional outcome at smaller ICH volume levels, and 14% [4%; 46%] at larger ICH volume levels. Higher ICH volume at admission and brainstem or intraventricular location of ICH were associated with neurological deterioration, while younger age, normotension, lower ICH volumes, and lobar location of ICH were predictors for neurological improvement. CONCLUSION: NIHSS at admission reflects 14% of the functional outcome at discharge for larger hematoma volumes and 30% for smaller hematoma volumes. These results underscore the importance of effects not reflected in NIHSS admission for the outcome of ICH patients such as secondary brain injury and early rehabilitation.

Iatrogenic cerebral amyloid angiopathy: A multinational case series and individual patient data analysis of the literature.

BACKGROUND: The transmission of amyloid ß (Aß) in humans leading to iatrogenic cerebral amyloid angiopathy (iCAA) is a novel concept with analogies to prion diseases. However, the number of published cases is low, and larger international studies are missing. AIMS: We aimed to build a large multinational collaboration on iCAA to better understand the clinical spectrum of affected patients. METHODS: We collected clinical data on patients with iCAA from Austria, Croatia, Italy, Slovenia, and Spain. Patients were included if they met the proposed Queen Square diagnostic criteria (QSC) for iCAA. In addition, we pooled data on disease onset, latency, and cerebrospinal fluid (CSF) biomarkers from previously published iCAA cases based on a systematic literature review. RESULTS: Twenty-seven patients (22% women) were included in this study. Of these, 19 (70%) met the criteria for probable and 8 (30%) for possible iCAA. Prior neurosurgical procedures were performed in all patients (93% brain surgery, 7% spinal surgery) at median age of 8 (interquartile range (IQR) = 4-18, range = 0-26 years) years. The median symptom latency was 39 years (IQR = 34-41, range = 28-49). The median age at symptom onset was 49 years (IQR = 43-55, range = 32-70). Twenty-one patients (78%) presented with intracranial hemorrhage and 3 (11%) with seizures. CONCLUSIONS: Our large international case series of patients with iCAA confirms a wide age boundary for the diagnosis of iCAA. Dissemination of awareness of this rare condition will help to identify more affected patients.

A Case Series of Four Patients with Artery of Percheron Occlusion over a Three-Month Period.

Here, we present a case series of four patients diagnosed with acute ischaemic stroke due to occlusion of the artery of Percheron (AOP), a rare stroke variant, observed in a single emergency centre within a three-month period. AOP occlusion is characterized by bilateral thalamic infarction with or without involvement of the mesencephalon. The presenting symptoms are diverse and not specific, but commonly include disturbance of consciousness, memory impairment, and vertical gaze palsy. In addition, due to the location of the infarction, imaging recognition is challenging and AOP occlusion often remains undiagnosed. This paper emphasizes the necessity of early recognition and appropriate management of AOP occlusion to significantly impact patient outcomes. Moreover, we argue that the condition might be more common than previously thought and that misdiagnosis or delay in diagnosis may lead to inappropriate treatment and potential failure to apply thrombolysis within the required timeframe.

Apixaban for the Treatment of Cerebral Venous Sinus Thrombosis: A Single-Centre Experience and Systematic Review of the Literature.

BACKGROUND AND OBJECTIVE: Cerebral venous thrombosis (CVT) is a rare disease, and data regarding direct oral anticoagulant therapy are insufficient. Apixaban could have a safer profile than other direct oral anticoagulants. We present our case series of patients with CVT treated with apixaban and a systematic review of published real-world cases. METHODS: We described our series of patients with CVT treated with apixaban and searched PubMed for similar published cases with reported complete outcome data: recanalisation rate, recurrent CVT, modified Rankin score, intracranial haemorrhage, other bleedings and mortality. RESULTS: Four male patients (average age 43.5 years) with idiopathic CVT, who presented with a headache and/or seizure without neurological deficits/symptoms or cerebral infarcts/haemorrhage were treated with apixaban 5 mg twice daily for an average 28 months (18-46 months) and followed for on average 2.8 years. In two patients, a partial/complete recanalisation was achieved, there was no recurrent CVT, all patients achieved a modified Rankin score of 0, none experienced an intracranial haemorrhage, other bleedings or died. One patient, in whom anti-phospholipid syndrome was later diagnosed, had a recurrence of CVT after stopping apixaban. Our systematic review identified only 15 eligible patients (average age 39 years, 60% female). Partial/complete recanalisation was achieved in 74% of cases, there was no recurrent CVT, 95% achieved a modified Rankin score of ≤ 2, none experienced an intracranial haemorrhage, other bleedings or died. CONCLUSIONS: Our cases and the review of similar published cases, albeit obtained on a smaller scale, suggest that apixaban may be a safe and effective therapy for CVT. This assumption should be tested in a large randomised study.