Publications by authors named "Anne Hege Aamodt"

32 Publications

Vaccine Induced Immune Thrombotic Thrombocytopenia Causing a Severe Form of Cerebral Venous Thrombosis With High Fatality Rate: A Case Series.

Front Neurol 2021 30;12:721146. Epub 2021 Jul 30.

Faculty of Medicine, Institute of Clinical Medicine, University in Oslo, Oslo, Norway.

During a 2-week period, we have encountered five cases presenting with the combination of cerebral venous thrombosis (CVT), intracerebral hemorrhage and thrombocytopenia. A clinical hallmark was the rapid and severe progression of disease in spite of maximum treatment efforts, resulting in fatal outcome in for 4 out of 5 patients. All cases had received ChAdOx1 nCov-19 vaccine 1-2 weeks earlier and developed a characteristic syndrome thereafter. The rapid progressive clinical course and high fatality rate of CVT in combination with thrombocytopenia in such a cluster and in otherwise healthy adults is a recent phenomenon. Cerebral autopsy findings were those of venous hemorrhagic infarctions and thrombi in dural venous sinuses, including thrombus material apparently rich in thrombocytes, leukocytes and fibrin. Vessel walls were free of inflammation. Extra-cerebral manifestations included leech-like thrombi in large veins, fibrin clots in small venules and scattered hemorrhages on skin and membranes. CVT with thrombocytopenia after adenovirus vectored COVID-19 vaccination is a new clinical syndrome that needs to be recognized by clinicians, is challenging to treat and seems associated with a high mortality rate.
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http://dx.doi.org/10.3389/fneur.2021.721146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363077PMC
July 2021

Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination.

N Engl J Med 2021 06 9;384(22):2124-2130. Epub 2021 Apr 9.

From the Departments of Hematology (N.H.S., G.E.T., P.A.H.), Immunology (L.A.M., F.L.-J.), Neurosurgery (M.W.), Neurology (A.-H.A.), and Radiology and Nuclear Medicine (T.H.S.), and the Research Institute of Internal Medicine (N.H.S., A.E.M., P.A.H.), Oslo University Hospital, and the Faculty of Medicine (A.E.M., G.E.T., P.A.H.), the KG Jebsen Center for B Cell Malignancy (L.A.M., G.E.T.), Institute of Clinical Medicine, and the ImmunoLingo Convergence Center (F.L.-J.), University of Oslo, the Department of Hematology, Akershus University Hospital, Lørenskog (N.H.S.), and the Norwegian National Unit for Platelet Immunology, Division of Diagnostics, University Hospital of North Norway, Tromsø (I.H.S., M.T.A.) - all in Norway.

We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4-polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.
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http://dx.doi.org/10.1056/NEJMoa2104882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112568PMC
June 2021

Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19.

J Neurol 2021 Oct 20;268(10):3574-3583. Epub 2021 Mar 20.

Department of Neurology, Oslo University Hospital, Oslo, Norway.

Objective: To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients.

Methods: Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects.

Results: In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 × 10) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02).

Conclusion: Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
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http://dx.doi.org/10.1007/s00415-021-10517-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980743PMC
October 2021

Cerebral venous thrombosis after COVID-19.

Tidsskr Nor Laegeforen 2020 12 14;140(18). Epub 2020 Dec 14.

Background: There is emerging evidence of an increased risk of venous thromboembolism as well as several reports of cerebral venous thrombosis in COVID-19.

Case Presentation: A previously healthy man in his fifties was admitted due to sudden confusion and reduced consciousness. One month earlier the patient had symptoms with headache, fever, dry cough, vomiting and diarrhoea and reduced sense of taste and smell. He was diagnosed with COVID-19 and the symptoms were mainly resolved within three weeks. On admission the patient was disorientated with aphasia. Brain imaging revealed a haemorrhagic infarction in the left temporal lobe due to thrombosis of the left transverse sinus and low-molecular weight heparin was instituted. On follow-up four months later, there was clinical improvement with only slight problems with short term memory and concentration.

Interpretation: This case illustrates the risk of serious neurological complications due to cerebral venous thrombosis in COVID-19.
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http://dx.doi.org/10.4045/tidsskr.20.0563DOI Listing
December 2020

How does COVID-19 affect the brain?

Tidsskr Nor Laegeforen 2020 06 29;140(10). Epub 2020 May 29.

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http://dx.doi.org/10.4045/tidsskr.20.0444DOI Listing
June 2020

Atrial fibrillation in cryptogenic stroke and transient ischaemic attack - The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Rationale and design.

Eur Stroke J 2019 Jun 19;4(2):172-180. Epub 2019 Mar 19.

Department of Neurology, Innlandet Hospital Trust, Lillehammer, Norway.

Purpose: Paroxysmal atrial fibrillation is often suspected as a probable cause of cryptogenic stroke. Continuous long-term ECG monitoring using insertable cardiac monitors is a clinically effective technique to screen for atrial fibrillation and superior to conventional follow-up in cryptogenic stroke. However, more studies are needed to identify factors which can help selecting patients with the highest possibility of detecting atrial fibrillation with prolonged rhythm monitoring. The clinical relevance of short-term atrial fibrillation, the need for medical intervention and the evaluation as to whether intervention results in improved clinical outcomes should be assessed.

Method: The Nordic Atrial Fibrillation and Stroke Study is an international, multicentre, prospective, observational trial evaluating the occurrence of occult atrial fibrillation in cryptogenic stroke and transient ischaemic attack. Patients with cryptogenic stroke or transient ischaemic attack from the Nordic countries are included and will have the Reveal LINQ® Insertable cardiac monitor system implanted for 12 months for atrial fibrillation detection. Biomarkers which can be used as predictors for atrial fibrillation and may identify patients, who could derive the most clinical benefit from the detection of atrial fibrillation by prolonged monitoring, are being studied.

Conclusion: The primary endpoint is atrial fibrillation burden within 12 months of continuous rhythm monitoring. Secondary endpoints are atrial fibrillation burden within six months, levels of biomarkers predicting atrial fibrillation, CHADS-VASc score, incidence of recurrent stroke or transient ischaemic attack, use of anticoagulation and antiarrhythmic drugs, and quality of life measurements. The clinical follow-up period is 12 months. The study started in 2017 and the completion is expected at the end of 2020.
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http://dx.doi.org/10.1177/2396987319837089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591764PMC
June 2019

Persistent postural-perceptual dizziness

Tidsskr Nor Laegeforen 2019 May 27;139(9). Epub 2019 May 27.

Persistent symptoms of dizziness may be due to inappropriate compensatory strategies following an episode of acute dizziness. Common symptoms are dizziness in an upright position that is aggravated by visual stimuli and passive movement. In the World Health Organization’s new disease classification, ICD-11, the condition has been named persistent postural-perceptual dizziness. It is important to recognise this condition in order to avoid unnecessary investigation and to initiate the correct treatment.
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http://dx.doi.org/10.4045/tidsskr.18.0962DOI Listing
May 2019

Tenecteplase Versus Alteplase Between 3 and 4.5 Hours in Low National Institutes of Health Stroke Scale.

Stroke 2019 02;50(2):498-500

Department of Neurology (V.N., C.E.K., H.N., U.W.-A., L.T.), Haukeland University Hospital, Bergen, Norway.

Background and Purpose- Thrombolysis with alteplase has beneficial effect on outcome and is safe within 4.5 hours. The present study compares the efficacy and safety of tenecteplase and alteplase in patients treated 3 to 4.5 hours after ischemic stroke. Methods- The data are from a prespecified substudy of patients included in The NOR-TEST (Norwegian Tenecteplase Stroke Trial), a randomized control trial comparing tenecteplase with alteplase. Results- The median admission National Institutes of Health Stroke Scale for this study population was 3 (interquartile range, 2-6). In the intention-to-treat analysis, 57% of patients that received tenecteplase and 53% of patients that received alteplase reached good functional outcome (modified Rankin Scale score of 0-1) at 3 months (odds ratio, 1.19; 95% CI, 0.68-2.10). The rates of intracranial hemorrhage in the first 48 hours were 5.7% in the tenecteplase group and 6.7% in the alteplase group (odds ratio, 0.84; 95% CI, 0.26-2.70). At 3 months, mortality was 5.7% and 4.5%, respectively. After excluding stroke mimics and patients with modified Rankin Scale score of >1 before stroke, the proportion of patients with good functional outcome was 61% in the tenecteplase group and 57% in the alteplase group (odds ratio, 1.24; 95% CI, 0.65-2.37). Conclusions- Tenecteplase is at least as effective as alteplase to achieve a good clinical outcome in patients with mild stroke treated between 3 and 4.5 hours after ischemic stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.
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http://dx.doi.org/10.1161/STROKEAHA.118.024223DOI Listing
February 2019

The correct dosage of mobilisation.

Authors:
Anne Hege Aamodt

Tidsskr Nor Laegeforen 2018 10 30;138(17). Epub 2018 Oct 30.

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http://dx.doi.org/10.4045/tidsskr.18.0769DOI Listing
October 2018

Migraine and stroke.

Tidsskr Nor Laegeforen 2018 02 19;138(4). Epub 2018 Feb 19.

Bakgrunn: Migrene er en vanlig nevrologisk sykdom som medfører betydelig belastning for den enkelte som rammes, og store helseøkonomiske kostnader for samfunnet. Migrene er forbundet med økt risiko for hjerneslag. Formålet med denne artikkelen er å gi en oversikt over sammenhengen mellom migrene og hjerneslag: både hjerneinfarkt og hjerneblødning, mulige underliggende mekanismer, kliniske implikasjoner og behovet for videre forskning innen feltet.

Kunnskapsgrunnlag: Denne oversikten er basert på litteratursøk i PubMed med definert søkestreng supplert med et pyramidesøk i søkemotoren McMaster PLUS med ordene «migraine» og «stroke», samt gjennomgang av artiklenes referanselister.

Resultat: Migrene med aura er assosiert med en dobling av risikoen for hjerneinfarkt, men det er ingen sikker økt risiko blant personer med migrene uten aura. Røyking, p-pillebruk og hyppige migreneanfall øker risikoen. Det ser også ut til å være en noe høyere forekomst av hjerneblødning hos personer med migrene med og uten aura.

Fortolkning: Sammenhengen mellom migrene og hjerneslag er kompleks. Det er med bakgrunn i økt risiko for hjerneinfarkt ved migrene med aura anbefalt at modifiserbare risikofaktorer som røyking, hypertensjon og p-pillebruk kartlegges grundig og behandles.
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http://dx.doi.org/10.4045/tidsskr.17.0347DOI Listing
February 2018

Increased Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Ischemic Stroke and Transient Ischemic Attack.

J Am Heart Assoc 2018 01 12;7(2). Epub 2018 Jan 12.

Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway

Background: Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been shown to be increased in patients with acute ischemic stroke. Here, we evaluated plasma sLOX-1 levels and vascular carotid plaque LOX-1 (ie, ) gene expression in patients with ischemic stroke and transient ischemic attack (TIA) with particular focus on their relation to time since symptom onset.

Methods And Results: Plasma sLOX-1 (n=232) and carotid plaque gene expression (n=146) were evaluated in patients who were referred to evaluation for carotid endarterectomy, as well as in healthy control plasma (n=81). Patients were categorized according to presence of acute ischemic stroke or transient ischemic attack (n=35) ≤7 days, >7 days ≤3 months (n=90), >3 months (n=40), or no reported symptoms before study inclusion (n=67). Our major findings were the following: (1) Patients with carotid atherosclerosis had increased plasma sLOX-1 levels as compared with controls. (2) Plaque mRNA levels were increased in carotid plaques (n=146) compared with nonatherosclerotic vessels (ie, common iliac arteries of organ donors, n=10). (3) There were no differences in sLOX plasma levels or gene expression when analyzed according to the time since relevant cerebral ischemic symptoms. (4) Also patients with severe carotid atherosclerosis without any previous ischemic events had raised sLOX-1 levels. (5) Immunostaining showed colocalization between LOX-1 and macrophages within the carotid plaques. (6) Also patients with acute stroke (within 7 days) caused by atrial fibrillation (n=22) had comparable raised sLOX-1 levels.

Conclusions: sLOX-1 levels are elevated in patients with ischemic stroke and transient ischemic attack independent of cause and time since the ischemic event.
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http://dx.doi.org/10.1161/JAHA.117.006479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850141PMC
January 2018

[Tenecteplase in acute cerebral infarction].

Tidsskr Nor Laegeforen 2018 01 8;138(1). Epub 2018 Jan 8.

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http://dx.doi.org/10.4045/tidsskr.17.0992DOI Listing
January 2018

Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial.

Lancet Neurol 2017 10 2;16(10):781-788. Epub 2017 Aug 2.

Department of Neurology, Centre for Neurovascular Diseases, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Background: Tenecteplase is a newer thrombolytic agent with some pharmacological advantages over alteplase. Previous phase 2 trials of tenecteplase in acute ischaemic stroke have shown promising results. We aimed to investigate the safety and efficacy of tenecteplase versus alteplase in patients with acute stroke who were eligible for intravenous thrombolysis.

Methods: This phase 3, randomised, open-label, blinded endpoint, superiority trial was done in 13 stroke units in Norway. We enrolled adults with suspected acute ischaemic stroke who were eligible for thrombolysis and admitted within 4·5 h of symptom onset or within 4·5 h of awakening with symptoms, or who were eligible for bridging therapy before thrombectomy. Patients were randomly assigned (1:1) to receive intravenous tenecteplase 0·4 mg/kg (to a maximum of 40 mg) or alteplase 0·9 mg/kg (to a maximum of 90 mg), via a block randomisation schedule stratified by centre of inclusion. Patients were not informed of treatment allocation; treating physicians were aware of treatment allocation but those assessing the primary and secondary endpoints were not. The primary outcome was excellent functional outcome defined as modified Rankin Scale (mRS) score 0-1 at 3 months. The primary analysis was an unadjusted and non-stratified intention-to-treat analysis with last observation carried forward for imputation of missing data. This study is registered with ClinicalTrials.gov, number NCT01949948.

Findings: Between Sept 1, 2012, and Sept 30, 2016, 1107 patients met the inclusion criteria and seven patients were excluded because informed consent was withdrawn or eligibility for thrombolytic treatment was reconsidered. 1100 patients were randomly assigned to the tenecteplase (n=549) or alteplase (n=551) groups. The median age of participants was 77 years (IQR 64-79) and the median National Institutes of Health Stroke Scale score at baseline was 4 points (IQR 2-8). A final diagnosis other than ischaemic stroke or transient ischaemic attack was found in 99 (18%) patients in the tenecteplase group and 91 (17%) patients in the alteplase group. The primary outcome was achieved by 354 (64%) patients in the tenecteplase group and 345 (63%) patients in the alteplase group (odds ratio 1·08, 95% CI 0·84-1·38; p=0·52). By 3 months, 29 (5%) patients had died in the tenecteplase group compared with 26 (5%) in the alteplase group. The frequency of serious adverse events was similar between groups (145 [26%] in the tenecteplase group vs 141 [26%] in the alteplase group; p=0·74).

Interpretation: Tenecteplase was not superior to alteplase and showed a similar safety profile. Most patients enrolled in this study had mild stroke. Further trials are needed to establish the safety and efficacy in patients with severe stroke and whether tenecteplase is non-inferior to alteplase.

Funding: Research Council of Norway.
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http://dx.doi.org/10.1016/S1474-4422(17)30253-3DOI Listing
October 2017

New anticoagulants in combination with antiplatelet agents.

Tidsskr Nor Laegeforen 2016 10 11;136(18):1543-1546. Epub 2016 Oct 11.

Medisinsk avdeling Sykehuset Østfold og Institutt for klinisk medisin Universitetet i Oslo.

The use of new, direct anticoagulants is increasing. Data from both controlled trials and clinical practice have shown that these drugs are as efficacious and safe as warfarin for deep vein thrombosis and pulmonary embolism, and as stroke prophylaxis for patients with atrial fibrillation. But what if platelet inhibition is also indicated? In the following, the combination of antiplatelets and the new anticoagulants is discussed for various indications.
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http://dx.doi.org/10.4045/tidsskr.15.1356DOI Listing
October 2016

Cerebral foreign body reaction after carotid aneurysm stenting.

Interv Neuroradiol 2016 Feb 28;22(1):53-7. Epub 2015 Oct 28.

Department of Neurology, Oslo University Hospital, Rikshospitalet, Norway

Flow diverter stents are new important tools in the treatment of large, giant, or wide-necked aneurysms. Their delivery and positioning may be difficult due to vessel tortuosity. Common adverse events include intracranial hemorrhage and ischemic stroke, which usually occurs within the same day, or the next few days after the procedure. We present a case where we encountered an unusual intracerebral complication several months after endovascular treatment of a large left internal carotid artery aneurysm, and where brain biopsy revealed foreign body reaction to hydrophilic polymer fragments distally to the stent site. Although previously described, embolization of polymer material from intravascular equipment is rare. We could not identify any other biopsy verified case in the literature, with this particular presentation of intracerebral polymer embolization--a multifocal inflammation spread out through the white matter of one hemisphere without hemorrhage or ischemic changes.
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http://dx.doi.org/10.1177/1591019915609171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757375PMC
February 2016

Pseudoperipheral palsy: a case of subcortical infarction imitating peripheral neuropathy.

BMC Neurol 2015 Aug 25;15:151. Epub 2015 Aug 25.

Dept of Neurology, Oslo University Hospital, Oslo, Norway.

Background: Vascular damage in the central hand knob area can mimic peripheral motor nerve deficits.

Case Presentation: We describe the case of a woman presenting with apparent peripheral neuropathy. Brain magnetic resonance imaging and computed tomography angiography revealed an infarct in the precentral hand knob area, with significant stenosis in the right proximal middle cerebral artery trunk. Subsequent 3-Tesla magnetic resonance imaging of the brain suggested cerebral angiitis. The patient experienced improved hand function following combined glucocorticoid and cyclophosphamide treatment.

Conclusion: Vascular damage in the hand knob area should be considered when evaluating peripheral motor nerve deficits in the presence of normal nerve conduction velocities. The diagnosis of cerebral angiitis remains a major challenge for clinicians.
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http://dx.doi.org/10.1186/s12883-015-0409-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566418PMC
August 2015

A pragmatic approach to sonothrombolysis in acute ischaemic stroke: the Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS).

BMC Neurol 2015 Jul 11;15:110. Epub 2015 Jul 11.

Department of Neurology, Haukeland University Hospital, N-5021, Bergen, Norway.

Background: Ultrasound accelerates thrombolysis with tPA (sonothrombolysis). Ultrasound in the absence of tPA also accelerates clot break-up (sonolysis). Adding intravenous gaseous microbubbles may potentiate the effect of ultrasound in both sonothrombolysis and sonolysis. The Norwegian Sonothrombolysis in Acute Stroke Study aims in a pragmatic approach to assess the effect and safety of contrast enhanced ultrasound treatment in unselected acute ischaemic stroke patients.

Methods/design: Acute ischaemic stroke patients ≥ 18 years, with or without visible arterial occlusion on computed tomography angiography (CTA) and treatable ≤ 4(½) hours after symptom onset, are included in NOR-SASS. NOR-SASS is superimposed on a separate trial randomising patients with acute ischemic stroke to either tenecteplase or alteplase (The Norwegian Tenecteplase Stroke Trial NOR-TEST). The NOR-SASS trial has two arms: 1) the thrombolysis-arms (NOR-SASS A and B) includes patients given intravenous thrombolysis (tenecteplase or alteplase), and 2) the no-thrombolysis-arm (NOR-SASS C) includes patients with contraindications to thrombolysis. First step randomisation of NOR-SASS A is embedded in NOR-TEST as a 1:1 randomisation to either tenecteplase or alteplase. Second step NOR-SASS randomisation is 1:1 to either contrast enhanced sonothrombolysis (CEST) or sham CEST. Randomisation in NOR-SASS B (routine alteplase group) is 1:1 to either CEST or sham CEST. Randomisation of NOR-SASS C is 1:1 to either contrast enhanced sonolysis (CES) or sham CES. Ultrasound is given for one hour using a 2-MHz pulsed-wave diagnostic ultrasound probe. Microbubble contrast (SonoVue®) is given as a continuous infusion for ~30 min. Recanalisation is assessed at 60 min after start of CEST/CES. Magnetic resonance imaging and angiography is performed after 24 h of stroke onset. Primary study endpoints are 1) major neurological improvement measured with NIHSS score at 24 h and 2) favourable functional outcome defined as mRS 0-1 at 90 days.

Discussion: NOR-SASS is the first randomised controlled trial designed to test the superiority of contrast enhanced ultrasound treatment given ≤ 4(½) hours after stroke onset in an unselected acute ischaemic stroke population eligible or not eligible for intravenous thrombolysis, with or without a defined arterial occlusion on CTA. If a positive effect and safety can be proven, contrast enhanced ultrasound treatment will be an option for all acute ischaemic stroke patients. EudraCT No 201200032341; www.clinicaltrials.gov NCT01949961.
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http://dx.doi.org/10.1186/s12883-015-0359-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499181PMC
July 2015

The Norwegian tenecteplase stroke trial (NOR-TEST): randomised controlled trial of tenecteplase vs. alteplase in acute ischaemic stroke.

BMC Neurol 2014 May 15;14:106. Epub 2014 May 15.

Center for Neurovascular Diseases, Haukeland University Hospital, Bergen, Norway.

Background: Alteplase is the only approved thrombolytic agent for acute ischaemic stroke. The overall benefit from alteplase is substantial, but some evidence indicates that alteplase also has negative effects on the ischaemic brain. Tenecteplase may be more effective and less harmfull than alteplase, but large randomised controlled phase 3 trials are lacking. The Norwegian Tenecteplase Stroke Trial (NOR-TEST) aims to compare efficacy and safety of tenecteplase vs. alteplase.

Methods/design: NOR-TEST is a multi-centre PROBE (prospective randomised, open-label, blinded endpoint) trial designed to establish superiority of tenecteplase 0.4 mg/kg (single bolus) as compared with alteplase 0.9 mg/kg (10% bolus + 90% infusion/60 minutes) for consecutively admitted patients with acute ischaemic stroke eligible for thrombolytic therapy, i.e. patients a) admitted <4½ hours after symptoms onset; b) admitted <4½ hours after awakening with stroke symptoms c) receiving bridging therapy before embolectomy.Randomisation tenecteplase:alteplase is 1:1. The primary study endpoint is favourable functional outcome defined as modified Rankin Scale 0-1 at 90 days. Secondary study endpoints are: 1) haemorrhagic transformation (haemorrhagic infarct/haematoma); 2) symptomatic cerebral haemorrhage on CT 24-48 hours; 3) major neurological improvement at 24 hours; 4) recanalisation at 24-36 hours; 5) death.

Discussion: NOR-TEST may establish a novel approach to acute ischaemic stroke treatment. A positive result will lead to a more effective, safer and easier treatment for all acute ischaemic stroke pasients.NOR-TEST is reviewed and approved by the Regional Committee for Medical and Health Research Ethics (2011/2435), and The Norwegian Medicines Agency (12/01402). NOR-TEST is registered with EudraCT No 2011-005793-33 and in ClinicalTrials.gov (NCT01949948).
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http://dx.doi.org/10.1186/1471-2377-14-106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029902PMC
May 2014

[Septic embolus].

Tidsskr Nor Laegeforen 2014 May 13;134(9):945. Epub 2014 May 13.

Nevrologisk avdeling Oslo universitetssykehus.

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http://dx.doi.org/10.4045/tidsskr.13.1656DOI Listing
May 2014

[Atrial fibrillation and stroke].

Tidsskr Nor Laegeforen 2013 Aug;133(14):1453-7

Nevrologisk avdeling, Klinikk for kirurgi og nevrofag, Oslo universitetssykehus, Rikshospitalet, Norway.

Background: More than 70,000 Norwegians have atrial fibrillation, which is a major risk factor for ischemic stroke. A large proportion of ischemic strokes caused by atrial fibrillation could be prevented if patients receive optimal prophylactic treatment. This article describes the risk for ischemic stroke in patients with atrial fibrillation, and discusses who should receive prophylactic treatment and which therapy provides the best prevention.

Method: The article is based on recently published European, American and Canadian guidelines, a search in PubMed and the authors' own clinical experience.

Results: The new risk score CHA2DS2-VASc is better than the CHADS2 score for identifying patients with atrial fibrillation who have a truly low risk of ischemic stroke and are not in need of antithrombotic treatment. Oral anticoagulation therapy is recommended for patients with two or more risk factors for thromboembolism in addition to atrial fibrillation (CHA2DS2-VASc ≥ 2). Patients with atrial fibrillation and a single additional risk factor (CHA2DS2-VASc =1) an individual assessment should be made as to who should receive oral anticoagulants, and for patients with CHA2DS2-VASc = 0 antithrombotic treatment is not recommended. New oral anticoagulants are at least as effective as warfarin for preventing ischemic stroke in patients with nonvalvular atrial fibrillation, they carry a lower risk of cerebral haemorrhage, especially intracranial haemorrhage and are more practical in use. Platelet inhibitors have a minimal role in stroke prevention in patients with atrial fibrillation.

Interpretation: Risks stratifying patients using the CHA2DS2-VASc score is a better method for assessing which patients with atrial fibrillation who should receive oral anticoagulation. The introduction of new oral anticoagulants will simplify preventive treatment and hopefully lead to a more efficient anticoagulation treatment in a larger number of patients with atrial fibrillation.
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http://dx.doi.org/10.4045/tidsskr.12.0850DOI Listing
August 2013

When every minute counts.

Authors:
Anne Hege Aamodt

Tidsskr Nor Laegeforen 2013 Jun;133(12-13):1324

Department of Neurology, Division of Surgery and Clinical Neuroscience, Oslo University Hospital, Rikshospitalet, Norway.

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http://dx.doi.org/10.4045/tidsskr.13.0627DOI Listing
June 2013

The validity of questionnaire-based diagnoses: the third Nord-Trøndelag Health Study 2006-2008.

J Headache Pain 2010 Feb 28;11(1):67-73. Epub 2009 Nov 28.

Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway.

The Nord-Trøndelag Health Study (HUNT 3) performed in 2006-2008 is a replication of the cross-sectional survey from 1995 to 1997 (HUNT 2). The aim of the present study was to assess the sensitivity and specificity of questionnaire-based headache diagnoses using a personal interview by a neurologist as a gold standard. For the questionnaire-based status as headache sufferer, a sensitivity of 88%, a specificity of 86%, and a kappa statistic of 0.70 were found. Chronic headache, chronic tension-type headache (TTH), and medication overuse headache (MOH) were diagnosed with a specificity of > or =99%, and a kappa statistic of > or =0.73. Lower figures were found for the diagnoses of migraine and TTH. For individuals with headache > or =1 day per month, a sensitivity of 58% (migraine) and 96% (TTH), a specificity of 91 and 69%, and a kappa statistic of 0.54 and 0.44 were found, respectively. The specificity for migraine with aura was 95%. In conclusion, the HUNT 3-questionnaire is a valid tool for identifying headache sufferers, and diagnosing patients with chronic headache, including chronic TTH and MOH. The more moderate sensitivity for migraine and TTH makes the questionnaire-based diagnoses of migraine and TTH suboptimal for determining the prevalence. However, the high specificity of the questionnaire-based diagnosis of migraine, in particular for migraine with aura, makes the questionnaire a valid tool for diagnosing patients with migraine for genetic studies.
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http://dx.doi.org/10.1007/s10194-009-0174-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3452179PMC
February 2010
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