Recanalisation therapies for acute ischaemic stroke in patients on direct oral anticoagulants.

Direct oral anticoagulants (DOACs) have emerged as primary therapeutic option for stroke prevention in patients with atrial fibrillation. However, patients may have ischaemic stroke despite DOAC therapy and there is uncertainty whether those patients can safely receive intravenous thrombolysis or mechanical thrombectomy. In this review, we summarise and discuss current knowledge about different approaches to select patient. Time since last DOAC intake-as a surrogate for anticoagulant activity-is easy to use but limited by interindividual variability of drug pharmacokinetics and long cut-offs (>48 hours). Measuring anticoagulant activity using drug-specific coagulation assays showed promising safety results. Large proportion of patients at low anticoagulant activity seem to be potentially treatable but there remains uncertainty about exact safe cut-off values and limited assay availability. The use of specific reversal agents (ie, idarucizumab or andexanet alfa) prior to thrombolysis is a new emerging option with first data reporting safety but issues including health economics need to be elucidated. Mechanical thrombectomy appears to be safe without any specific selection criteria applied. In patients on DOAC therapy with large vessel occlusion, decision for intravenous thrombolysis should not delay thrombectomy (eg, direct thrombectomy or immediate transfer to a thrombectomy-capable centre recommended). Precision medicine using a tailored approach combining clinicoradiological information (ie, penumbra and vessel status), anticoagulant activity and use of specific reversal agents only if necessary seems a reasonable choice.

Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage.

OBJECTIVE: To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH. METHODS: Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC. RESULTS: IHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04-1.93) vs non-LDSH: 1.32 (0.33-3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38-4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4-6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume <4.4 mL: 0.18 (0.04-0.78); p=0.022) and low National Institutes of Health Stroke Scale (NIHSS) score on admission (OR: NIHSS <4: 0.29 (0.11-0.78); p=0.014) were significantly associated with fewer IHC. CONCLUSIONS: Heparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention.

Efficacy and safety of bridging thrombolysis initiated before transfer in a drip-and-ship stroke service.

OBJECTIVE: Data regarding the efficacy and safety of bridging thrombolysis (BT) initiated before transfer for evaluation of endovascular therapy is heterogeneous. We, therefore, analyse efficacy and safety of BT in patients treated within a drip-and-ship stroke service. METHODS: Consecutive adult patients suffering from acute ischaemic stroke and large-vessel occlusions (LVO) transferred to our comprehensive stroke centre for evaluation of endovascular therapy in 2017-2020 were identified from a local prospective stroke database and categorised according to BT and no-BT. BT was defined as intravenous thrombolysis initiated before transfer. LVO was assessed before and after transfer. Functional outcome before stroke and at 3 months using the modified Rankin scale (mRS) was determined. Excellent outcome was defined as mRS 0-1 or return to prestroke mRS. For safety analysis, intracranial haemorrhages and mortality at 3 months were analysed. Main analysis was limited to patients with anterior circulation stroke. RESULTS: Of N=714 patients, n=394 (55.2%) received BT. More patients in the BT group with documented LVO before transfer recanalised without endovascular therapy (n=46, 11.7%) than patients who did not receive BT before transfer (n=4, 1.3%, p<0.001). In multivariate analysis, BT was the strongest independent predictor of early recanalisation (adjusted OR 10.9, 95% CI 3.8 to 31.1, p<0.001). BT tended to be an independent predictor of an excellent outcome at 3 months (adjusted OR 1.38, 95% CI 0.97 to 1.96, p=0.077). There were no differences in safety between the BT and no-BT groups. CONCLUSIONS: BT initiated before transfer was a strong independent predictor of early recanalisation.

Manifestation of Intracranial Lesions at High Altitude: Case Report and Review of the Literature.

Speidel, Victor, Jan Christoph Purrucker, and Katarína Klobucníková. Manifestation of intracranial lesions at high altitude: case report and review of the literature. High Alt Med Biol. 22:87-89, 2021.-A 32-year-old man trekked to the South Everest Base Camp (5,364 m) in Nepal. On the last day of the ascent, he noticed some dysesthesia in his right leg and descended by helicopter. He suffered a generalized seizure shortly after his descent, followed by right-sided hemiparesis and speech arrest. Without the possibility of cerebral imaging, the patient was given dexamethasone intravenously who showed a marked improvement and regained the ability to speak. Magnetic resonance imaging later revealed a lesion in the left frontotemporal region with compression of brain parenchyma and minimal paralesional edema. A meningioma was later surgically resected. Although seizures are a common first manifestation of meningioma, we argue that the exposure to high altitude may have contributed to his symptoms, either by increasing the peritumoral edema by pathophysiology similar to high-altitude cerebral edema (HACE) or lowering the seizure threshold otherwise. This case shows a before unknown pre-existing condition becoming symptomatic at high altitude and illustrates the necessity for careful and immediate evaluation of every patient with new onset of unexplained focal neurological deficits or seizures at high altitude in addition to unspecific neurological symptoms commonly associated with HACE such as headaches, dizziness, lightheadedness, or ataxia.

Challenges of Acute Ischemic Stroke Treatment in Orally Anticoagulated Patients via Telemedicine.

BACKGROUND: Managing acute ischemic stroke (AIS) in patients receiving treatment with vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs) is difficult and the challenge this poses for stroke telemedicine remains unexplored. METHODS: We analyzed data from a random sample (n = 1500) of all teleneurological consultations conducted between July 2015 and December 2017. Management of patients suffering AIS with and without prior oral anticoagulation treatment was characterized, including potential vs. actual treatment with intravenous thrombolysis (IVT) and reasons for withholding it. RESULTS: n = 359 patients had suffered an AIS, of whom 63 (17.5%) were under treatment with oral anticoagulants (VKA, n = 24; NOAC, n = 39). Administration of IVT was more common in patients who had not received prior oral anticoagulation treatment (20.3% vs. 3.2%, p < 0.001). NOAC intake was the primary reason for withholding IVT in 37% of orally anticoagulated patients who were found potentially eligible for IVT. Furthermore, patients under oral anticoagulation tended to be transported to the comprehensive stroke center more often (23.8% vs. 13.9%, p = 0.056). CONCLUSIONS: AIS in patients on oral anticoagulation treatment is a frequent reason for telestroke consultation, and NOAC intake constitutes an important barrier to administering IVT.

Electronic Alberta Stroke Program Early CT score change and functional outcome in a drip-and-ship stroke service.

BACKGROUND: Debate continues as to whether patients with acute ischemic stroke with (suspected) large vessel occlusion benefit from direct referral versus secondary transportation. AIMS: To analyze the change in early infarct signs, collaterals, and acute ischemia volume and their association with transfer time and functional outcome. METHODS: We retrospectively analyzed consecutive transfers between 2013 and 2016 for patients with anterior circulation stroke transported from referring hospitals to our center as potential candidates for thrombectomy. Alberta Stroke Programme Early CT Scores (ASPECTS) were automatically calculated on external and in-house CT using the Brainomix e-ASPECTS software, and collaterals were assessed using the e-CTA tool. Functional status after stroke using the modified Rankin scale (mRS) was obtained. RESULTS: 102 patients with CT scans both at the referring hospital and our center were identified. During patient transfer, e-ASPECTS declined by a median of 1 point (0-2). Functional outcome correlated with the change in e-ASPECTS (decline, n=54) (Spearman rs =0.322, 95% CI 0.131 to 0.482, p=0.001). The median image-to-image time was 149 min (IQR 113-190), but did not correlate with change in e-ASPECTS (p=0.754) and mRS score at 3 months (p=0.25). Preserved good collateral status assessed at the comprehensive stroke center was associated with better functional outcome (rs =-0.271, 95% CI -0.485 to -0.037, p=0.02). CONCLUSIONS: Patient transfer in a drip-and-ship network was associated with declines in e-ASPECTS associated with worse functional outcome. Image-to-image time did not influence this association, but worsening collateral status did.

Design and validation of a clinical scale for prehospital stroke recognition, severity grading and prediction of large vessel occlusion: the shortened NIH Stroke Scale for emergency medical services.

OBJECTIVE: To develop an NIH Stroke Scale (NIHSS)-compatible, all-in-one scale for rapid and comprehensive prehospital stroke assessment including stroke recognition, severity grading and progression monitoring as well as prediction of large vessel occlusion (LVO). METHODS: Emergency medical services (EMS) personnel and stroke physicians (n=326) rated each item of the NIHSS regarding suitability for prehospital use; best rated items were included. Stroke recognition was evaluated retrospectively in 689 consecutive patients with acute stroke or stroke mimics, prediction of LVO in 741 consecutive patients with ischaemic stroke with acute vessel imaging independent of admission NIHSS score. RESULTS: Nine of the NIHSS items were rated as 'suitable for prehospital use.' After excluding two items in order to increase specificity, the final scale (termed shortened NIHSS for EMS, sNIHSS-EMS) consists of 'level of consciousness', 'facial palsy', 'motor arm/leg', 'sensory', 'language' and 'dysarthria'. Sensitivity for stroke recognition of the sNIHSS-EMS is 91% (95% CI 86 to 94), specificity 52% (95% CI 47 to 56). Receiver operating curve analysis revealed an optimal cut-off point for LVO prediction of ≥6 (sensitivity 70% (95% CI 65 to 76), specificity 81% (95% CI 76 to 84), positive predictive value 70 (95% CI 65 to 75), area under the curve 0.81 (95% CI 0.78 to 0.84)). Test characteristics were non-inferior to non-comprehensive scales. CONCLUSIONS: The sNIHSS-EMS may overcome the sequential use of multiple emergency stroke scales by permitting parallel stroke recognition, severity grading and LVO prediction. Full NIHSS-item compatibility allows for evaluation of stroke progression starting at the prehospital phase.