Ann De Smedt

Intravenous Thrombolysis with Recombinant Tissue Plasminogen Activator in a Stroke Patient Treated with Dabigatran

Apixaban is increasingly used in clinical practice (1), but data on the bleeding risk in patients treated with recombinant tissue plasminogen activator (rt-PA) while taking apixaban are nonexistent. A 74-year-old right-handed man presented with abrupt onset of global aphasia. He was known with a partial right hemianopsia secondary to a left occipital intracerebral hemorrhage five-years earlier and with paroxysmal nonvalvular atrial fibrillation treated with apixaban 5 mg bid. The National Institutes of Health Stroke Scale (NIHSS) score was 8. Noncontrast computed tomography (CT) of the brain showed no signs of acute intracranial pathology. Perfusion-CT revealed hypoperfusion in the territory of the left middle cerebral artery (Fig. 1a). An ostial stenosis of the left internal carotid artery was diagnosed on CT angiography (Fig. 1b). After informed consent by proxy, i.v. rt-PA therapy (0·9 mg/kg; total dose 81 mg) was administered at 4·5 h after symptom onset and 8·5 h after apixaban intake. Platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen levels were normal, as was creatinine clearance. The patient experienced an excellent recovery (NIHSS score 1) without signs of new infarction or intracranial hemorrhage on repeat CT. As apixaban is commonly used in patients with elevated stroke risk (1), therapeutic decision-making with regard to thrombolytic therapy may not uncommonly pose problems in the near future. Our case report illustrates that further study on the safety of rt-PA in this patient population is justified. Ann De Smedt*, Melissa Cambron, Koenraad Nieboer, Maarten Moens, Robbert-Jan Van Hooff, Laetitia Yperzeele, Kristin Jochmans, Jacques De Keyser, and Raf Brouns

Insulin-Like Growth Factor I Serum Levels Influence Ischemic Stroke Outcome

Background and Purpose— Insulin-like growth factor I (IGF-I) is neuroprotective in animal models of stroke. We investigated whether serum IGF-I levels in patients with acute ischemic stroke influence stroke severity and outcome. Methods— Concentrations of IGF-I and IGF binding protein 3 were measured in serum samples obtained within 6 hours after stroke onset from 255 patients who took part in the placebo arm of the United States and Canadian Lubeluzole in Acute Ischemic Stroke Study. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Multivariate analysis was performed to assess the overall shift in modified Rankin Scale score and changes in the National Institutes of Health Stroke Scale score at 3 months. Survival curves were plotted using the Kaplan-Meier method, and the Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival. Results— After controlling for statistically relevant risk factors, subjects with high IGF-I levels or IGF-I/IGF binding protein 3 ratios had a better neurological and functional outcome at 3 months. Baseline stroke severity was not different between high and low IGF-I groups. In contrast to the low IGF-I group, neurological symptoms gradually improved from Day 3 in the high IGF-I group. Conclusions— Our results suggest that high serum IGF-I levels just after ischemic stroke onset are associated with neurological recovery and a better functional outcome.

Prehospital Unassisted Assessment of Stroke Severity Using Telemedicine A Feasibility Study

Background and Purpose— We evaluated the feasibility and the reliability of remote stroke severity quantification in the prehospital setting using the Unassisted TeleStroke Scale (UTSS) via a telestroke ambulance system and a fourth-generation mobile network. Methods— The technical feasibility and the reliability of the UTSS were studied in healthy volunteers mimicking 41 stroke syndromes during ambulance transportation. Results— Except for 1 issue, high-quality telestroke assessment was feasible in all scenarios. The mean examination time for the UTSS was 3.1 minutes (SD, 0.4). The UTSS showed excellent intrarater and interrater variability (&rgr;=0.98 and 0.97; P<0.001), as well as excellent internal consistency and rater agreement. Adequate concurrent validity can be derived from the strong correlation between the UTSS and the National Institutes of Health Stroke Scale (&rgr;=0.90; P<0.001). Conclusions— Remote assessment of stroke severity in fast-moving ambulances using a system dedicated to prehospital telemedicine, 4G technology, and the UTSS is feasible and reliable.

Feasibility of AmbulanCe-Based Telemedicine (FACT) Study: Safety, Feasibility and Reliability of Third Generation In-Ambulance Telemedicine

Background Telemedicine is currently mainly applied as an in-hospital service, but this technology also holds potential to improve emergency care in the prehospital arena. We report on the safety, feasibility and reliability of in-ambulance teleconsultation using a telemedicine system of the third generation. Methods A routine ambulance was equipped with a system for real-time bidirectional audio-video communication, automated transmission of vital parameters, glycemia and electronic patient identification. All patients ( ≥18 years) transported during emergency missions by a Prehospital Intervention Team of the Universitair Ziekenhuis Brussel were eligible for inclusion. To guarantee mobility and to facilitate 24/7 availability, the teleconsultants used lightweight laptop computers to access a dedicated telemedicine platform, which also provided functionalities for neurological assessment, electronic reporting and prehospital notification of the in-hospital team. Key registrations included any safety issue, mobile connectivity, communication of patient information, audiovisual quality, user-friendliness and accuracy of the prehospital diagnosis. Results Prehospital teleconsultation was obtained in 41 out of 43 cases (95.3%). The success rates for communication of blood pressure, heart rate, blood oxygen saturation, glycemia, and electronic patient identification were 78.7%, 84.8%, 80.6%, 64.0%, and 84.2%. A preliminary prehospital diagnosis was formulated in 90.2%, with satisfactory agreement with final in-hospital diagnoses. Communication of a prehospital report to the in-hospital team was successful in 94.7% and prenotification of the in-hospital team via SMS in 90.2%. Failures resulted mainly from limited mobile connectivity and to a lesser extent from software, hardware or human error. The user acceptance was high. Conclusions Ambulance-based telemedicine of the third generation is safe, feasible and reliable but further research and development, especially with regard to high speed broadband access, is needed before this approach can be implemented in daily practice.

Prehospital Stroke Care: Limitations of Current Interventions and Focus on New Developments

Background: The global burden of stroke is immense, both in medical and economic terms. With the aging population and the ongoing industrialization of the third world, stroke prevalence is expected to increase and will have a major effect on national health expenditures. Currently, the medical treatment for acute ischemic stroke is limited to intravenous recombinant tissue plasminogen activator (IV r-tPA), but its time dependency leads to low utilization rates in routine clinical practice. Prehospital delay contributes significantly to delayed or missed treatment opportunities in acute stroke. State-of-the-art acute stroke care, starting in the prehospital phase, could thereby reduce the disease burden and its enormous financial costs. Summary: The first part of this review focuses on current education measures for the general public, the emergency medical services (EMS) dispatchers and paramedics. Although much has been expected of these measures to improve stroke care, no major effects on prehospital delay or missed treatment opportunities have been demonstrated over the years. Most interventional studies showed little or no effect on the onset-to-door time, IV r-tPA utilization rates or outcome, except for prenotification of the receiving hospital by the EMS. No data are currently available on the cost-effectiveness of these commonly used measures. In the second part, we discuss new developments for the improvement of prehospital stroke diagnosis and treatment which could open new perspectives in the nearby future. These include the implementation of prehospital telestroke and the deployment of mobile stroke units. These approaches may improve patient care and could serve as a platform for prehospital clinical trials. Other opportunities include the implementation of noninvasive diagnostics (like transcranial ultrasound and blood-borne biomarkers) and the reevaluation of neuroprotective strategies in the prehospital phase. Key Messages: Timely initiation of treatment can effectively reduce the medical and economic burden of stroke and should begin with optimal prehospital stroke care. For this, prehospital telemedicine is a particularly attractive approach because it is a scalable solution that has the potential to rapidly optimize acute stroke care at limited cost.

Heart rate variability and baroreceptor sensitivity in acute stroke : a systematic review

Background Autonomic nervous system dysfunction is common after acute stroke and is associated with elevated risk of cardiac arrhythmia and mortality. Heart rate variability and baroreceptor sensitivity have been investigated as parameters of autonomic nervous system dysfunction for the prediction of stroke outcome. Summary We performed a systematic literature review on heart rate variability and baroreceptor sensitivity as parameters for autonomic nervous function in acute stroke. Twenty-two studies were included. Associations between heart rate variability or baroreceptor sensitivity and stroke severity, early and late complications, dependency and mortality were reported. However, interpretability of most studies and extrapolation to general stroke population are limited due to many confounding factors such as varying methodology, small sample sizes, survival selection, and exclusion of patients with frequently occurring comorbidities in stroke. Key issues, such as the effect of thrombolytic therapy on autonomic function, autonomic nervous system dysfunction in the hyperacute phase of stroke, and correlation with the risk of recurrent stroke have not been investigated. Also, nonlinear techniques have remained largely unexplored in this domain, in spite of their advantage to provide more solid evaluation in the occurrence of arrhythmia. Key messages Cardiac autonomic dysfunction, represented by reduced heart rate variability or impaired baroreceptor sensitivity, is associated with stroke severity, early and late complications, dependency, and mortality. Large-scale prospective studies applying internationally accepted standards of measures for analysis of heart rate variability and baroreceptor sensitivity are needed in patients with acute stroke.

Unassisted Assessment of Stroke Severity Using Telemedicine

Background and Purpose— Quantification of stroke severity through telemedicine consultation is challenging and relies on professional support at the patient’s bedside. We aimed to develop a novel scale for assessing stroke severity through telemedicine without assistance from a third party (Unassisted TeleStroke Scale [UTSS]). Methods— Stroke severity was assessed in 45 patients with suspicion of acute stroke by bedside examination using the National Institutes of Health Stroke Scale (NIHSS) and by teleconsultation using the UTSS. Scale reliability was evaluated by intrarater and interrater variability, internal consistency, and rater agreement. Concurrent and predictive validity were tested by relating the UTSS with the NIHSS and long-term outcome (modified Rankin Scale and mortality at 6 months). Clinimetric analysis of the UTSS was obtained via the Rasch model. Results— The mean examination time for the UTSS was 3.1 minutes (SD, 1.1) versus 8.5 minutes for the NIHSS (SD, 2.6; P<0.001). Both UTSS and NIHSS showed excellent intrarater variability (r=0.97 and 0.98; P<0.001) and interrater variability (r=0.96 and 0.98; P<0.001), as well as excellent internal consistency and rater agreement. The UTSS correlated strongly with the NIHSS and was identified as an independent predictor of stroke outcome in logistic regression analysis. Rasch analysis indicated that the UTSS represents a unidimensional scale of stroke severity. Conclusions— The UTSS is a rapid, reliable, and valid tool for unassisted assessment of stroke severity through telemedicine.

Intravenous thrombolysis with recombinant tissue plasminogen activator in a stroke patient treated with apixaban

Apixaban is increasingly used in clinical practice (1), but data on the bleeding risk in patients treated with recombinant tissue plasminogen activator (rt-PA) while taking apixaban are nonexistent. A 74-year-old right-handed man presented with abrupt onset of global aphasia. He was known with a partial right hemianopsia secondary to a left occipital intracerebral hemorrhage five-years earlier and with paroxysmal nonvalvular atrial fibrillation treated with apixaban 5 mg bid. The National Institutes of Health Stroke Scale (NIHSS) score was 8. Noncontrast computed tomography (CT) of the brain showed no signs of acute intracranial pathology. Perfusion-CT revealed hypoperfusion in the territory of the left middle cerebral artery (Fig. 1a). An ostial stenosis of the left internal carotid artery was diagnosed on CT angiography (Fig. 1b). After informed consent by proxy, i.v. rt-PA therapy (0·9 mg/kg; total dose 81 mg) was administered at 4·5 h after symptom onset and 8·5 h after apixaban intake. Platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen levels were normal, as was creatinine clearance. The patient experienced an excellent recovery (NIHSS score 1) without signs of new infarction or intracranial hemorrhage on repeat CT. As apixaban is commonly used in patients with elevated stroke risk (1), therapeutic decision-making with regard to thrombolytic therapy may not uncommonly pose problems in the near future. Our case report illustrates that further study on the safety of rt-PA in this patient population is justified. Ann De Smedt*, Melissa Cambron, Koenraad Nieboer, Maarten Moens, Robbert-Jan Van Hooff, Laetitia Yperzeele, Kristin Jochmans, Jacques De Keyser, and Raf Brouns

Intravenous thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke in a patient treated with rivaroxaban.

Intravenous recombinant tissue plasminogen activator (IV rtPA) s the only approved therapy for acute ischemic stroke [1]. Interational guidelines stipulate that anticoagulant use is a (relative) ontraindication for treatment with IV rtPA. Rivaroxaban is an oral direct factor Xa inhibitor that is increasngly being used in routine clinical practice for primary prevention nd treatment of venous thromboembolism, stroke prevention in onvalvular atrial fibrillation and only in Europe as secondary preention in acute coronary syndromes [2]. It is therefore expected hat clinicians will be increasingly confronted with the question ow to treat acute ischemic stroke in these patients [3]. Data on the leeding risk in patients treated with IV rtPA while taking rivaroxban are lacking. Various commercial assays have been developed o measure the drug concentration, but as these are not yet widely vailable bedside [4], the prothrombin time (PT) is suggested as a imited alternative to assess the presence of anticoagulant effect, specially in urgent situations [5].

Feasibility of cerebral magnetic resonance imaging in patients with externalised spinal cord stimulator

OBJECT Spinal cord stimulation (SCS) is a well-known treatment option for intractable neuropathic pain after spinal surgery, but its pathophysiological mechanisms are poorly stated. The goal of this study is to analyse the feasibility of using brain MRI, functional MRI (fMRI) and Magnetic Resonance Spectroscopy (MRS) as tools to analyse these mechanisms in patients with externalised neurostimulators during trial period. METHODS The authors conducted in an in vitro and in vivo study analysing safety issues when performing brain MRI, fMRI and MRS investigations in human subjects with externalised SCS. Temperature measurements in vitro were performed simulating SCS during MRI sequences using head transmit-receive coils in 1.5 and 3 T MRI systems. 40 Patients with externalised SCS were included in the in vivo study. 20 patients underwent brain MRI, fMRI and another 20 patients underwent brain MRI and MRS. RESULTS A maximal temperature increase of 0.2°C was measured and neither electrode displacements nor hardware failures were observed. None of the patients undergoing the MRS sequences at the 1.5 or 3 T MRI scanners described any discomfort or unusual sensations. CONCLUSION We can conclude that brain MRI, fMRI and MRS studies performed in patients with externalised SCS can be safely executed.