Publications by authors named "Anders von Heijne"

23 Publications

  • Page 1 of 1

Detection of upper extremity deep vein thrombosis by magnetic resonance non-contrast thrombus imaging.

J Thromb Haemost 2021 May 21. Epub 2021 May 21.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.

Background: Compression ultrasonography (CUS) is the first-line imaging test for diagnosing upper extremity deep vein thrombosis (UEDVT), but often yields inconclusive test results. Contrast venography is still considered the diagnostic standard but is an invasive technique.

Objectives: We aimed to determine the diagnostic accuracy of magnetic resonance noncontrast thrombus imaging (MR-NCTI) for the diagnosis of UEDVT.

Methods: In this international multicenter diagnostic study, we prospectively included patients with clinically suspected UEDVT who were managed according to a diagnostic algorithm that included a clinical decision rule (CDR), D-dimer test, and diagnostic imaging. UEDVT was confirmed by CUS or (computed tomography [CT]) venography. UEDVT was excluded by (1) an unlikely CDR and normal D-dimer, (2) a normal serial CUS or (3) a normal (CT) venography. Within 48 h after the final diagnosis was established, patients underwent MR-NCTI. MR-NCTI images were assessed post hoc by two independent radiologists unaware of the presence or absence of UEDVT. The sensitivity, specificity, and interobserver agreement of MR-NCTI for UEDVT were determined.

Results: Magnetic resonance noncontrast thrombus imaging demonstrated UEDVT in 28 of 30 patients with UEDVT and was normal in all 30 patients where UEDVT was ruled out, yielding a sensitivity of 93% (95% CI 78-99) and specificity of 100% (95% CI 88-100). The interobserver agreement of MR-NCTI had a kappa value of 0.83 (95% CI 0.69-0.97).

Conclusions: Magnetic resonance noncontrast thrombus imaging is an accurate and reproducible method for diagnosing UEDVT. Clinical outcome studies should determine whether MR-NCTI can replace venography as the second-line imaging test in case of inconclusive CUS.
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http://dx.doi.org/10.1111/jth.15394DOI Listing
May 2021

Cost-effectiveness of magnetic resonance imaging for diagnosing recurrent ipsilateral deep vein thrombosis.

Blood Adv 2021 03;5(5):1369-1378

Department of Thrombosis and Hemostasis and.

The diagnostic workup of recurrent ipsilateral deep vein thrombosis (DVT) using compression ultrasonography (CUS) can be complicated by persistent intravascular abnormalities after a previous DVT. We showed that magnetic resonance direct thrombus imaging (MRDTI) can exclude recurrent ipsilateral DVT. However, it is unknown whether the application of MRDTI in daily clinical practice is cost effective. The aim of this study was to evaluate the cost effectiveness of MRDTI-based diagnosis for suspected recurrent ipsilateral DVT during first year of treatment and follow-up in the Dutch health care setting. Patient-level data of the Theia study (NCT02262052) were analyzed in 10 diagnostic scenarios, including a clinical decision rule and D-dimer test and imaging with CUS and/or MRDTI. The total costs of diagnostic tests and treatment during 1-year follow-up, including costs of false-positive and false-negative diagnoses, were compared and related to the associated mortality. The 1-year health care costs with MRDTI (range, €1219-1296) were generally lower than strategies without MRDTI (range, €1278-1529). This was because of superior specificity, despite higher initial diagnostic costs. Diagnostic strategies including CUS alone and CUS followed by MRDTI in case of an inconclusive CUS were potential optimal cost-effective strategies, with estimated average costs of €1529 and €1263 per patient and predicted mortality of 1 per 737 patients and 1 per 609 patients, respectively. Our model shows that diagnostic strategies with MRDTI for suspected recurrent ipsilateral DVT have generally lower 1-year health care costs than strategies without MRDTI. Therefore, compared with CUS alone, applying MRDTI did not increase health care costs.
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http://dx.doi.org/10.1182/bloodadvances.2020003849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948280PMC
March 2021

Hyperdense artery sign, symptomatic infarct swelling and effect of alteplase in acute ischaemic stroke.

Stroke Vasc Neurol 2020 Nov 27. Epub 2020 Nov 27.

Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK

Background: Alteplase improves functional outcomes of patients with acute ischaemic stroke, but its effects on symptomatic infarct swelling, an adverse complication of stroke and the influence of CT hyperdense artery sign (HAS) are unclear. This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association.

Methods: We included stroke patients whose prerandomisation scan was non-contrast CT. Raters, masked to clinical information, assessed baseline (prerandomisation) and follow-up (24-48 hours postrandomisation) CT scans for HAS, defined as an intracranial artery appearing denser than contralateral arteries. Symptomatic infarct swelling was defined as clinically significant neurological deterioration ≤7 days after stroke with radiological evidence of midline shift, effacement of basal cisterns or uncal herniation.

Results: Among 2961 patients, HAS presence at baseline was associated with higher risk of symptomatic infarct swelling (OR 2.21; 95% CI 1.42 to 3.44). Alteplase increased the risk of swelling (OR 1.69; 95% CI 1.11 to 2.57), with no difference between patients with and those without baseline HAS (p=0.49). In patients with baseline HAS, alteplase reduced the proportion with HAS at follow-up (OR 0.67; 95% CI 0.50 to 0.91), where HAS disappearance was associated with reduced risk of swelling (OR 0.25, 95% CI 0.14 to 0.47).

Conclusion: Although alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS, it was also associated with accelerated clearance of HAS, which in return reduced swelling, providing further mechanistic insights to underpin the benefits of alteplase.
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http://dx.doi.org/10.1136/svn-2020-000569DOI Listing
November 2020

Safety of using the combination of the Wells rule and D-dimer test for excluding acute recurrent ipsilateral deep vein thrombosis.

J Thromb Haemost 2020 09 21;18(9):2341-2348. Epub 2020 Jul 21.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.

Background: The diagnostic accuracy of clinical probability assessment and D-dimer testing for clinically suspected recurrent deep vein thrombosis (DVT) is largely unknown.

Aim: To evaluate the safety of ruling out acute recurrent DVT based on an unlikely Wells score for DVT and a normal D-dimer test.

Methods: This was a predefined endpoint of the Theia study in which the diagnostic accuracy of magnetic resonance direct thrombus imaging in acute recurrent ipsilateral DVT was validated. The Wells rule and D-dimer test, performed as part of the study protocol, were not used for management decisions. The primary outcome of this analysis was the incidence of recurrent DVT at baseline or during 3-month follow-up for patients with an unlikely Wells score and a normal D-dimer test.

Results: Results of both Wells score and D-dimer tests were available in 231 patients without anticoagulant treatment. The recurrent DVT prevalence was 45% (103/231). Forty-nine patients had an unlikely Wells score and normal D-dimer test, of whom 3 (6.1%, 95% confidence interval [CI] 1.3%-18%) had recurrent DVT at baseline/follow-up, yielding a sensitivity of 97% (95% CI 92%-99%) and specificity of 36% (95% CI 28%-45%). Thus, if clinical probability scoring and D-dimer testing would have been applied, radiological imaging could have been omitted in 21% of patients with a diagnostic failure rate of 6.1%.

Conclusion: By applying clinical probability scoring and D-dimer testing, radiological imaging could be spared in one fifth of patients with suspected recurrent ipsilateral DVT. However, the high failure rate does not support implementation of this strategy in daily practice.
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http://dx.doi.org/10.1111/jth.14986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497055PMC
September 2020

Magnetic resonance imaging for diagnosis of recurrent ipsilateral deep vein thrombosis.

Blood 2020 04;135(16):1377-1385

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.

The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) is challenging, because persistent intravascular abnormalities after previous DVT often hinder a diagnosis by compression ultrasonography. Magnetic resonance direct thrombus imaging (MRDTI), a technique without intravenous contrast and with a 10-minute acquisition time, has been shown to accurately distinguish acute recurrent DVT from chronic thrombotic remains. We have evaluated the safety of MRDTI as the sole test for excluding recurrent ipsilateral DVT. The Theia Study was a prospective, international, multicenter, diagnostic management study involving patients with clinically suspected acute recurrent ipsilateral DVT. Treatment of the patients was managed according to the result of the MRDTI, performed within 24 hours of study inclusion. The primary outcome was the 3-month incidence of venous thromboembolism (VTE) after a MRDTI negative for DVT. The secondary outcome was the interobserver agreement on the MRDTI readings. An independent committee adjudicated all end points. Three hundred five patients were included. The baseline prevalence of recurrent DVT was 38%; superficial thrombophlebitis was diagnosed in 4.6%. The primary outcome occurred in 2 of 119 (1.7%; 95% confidence interval [CI], 0.20-5.9) patients with MRDTI negative for DVT and thrombophlebitis, who were not treated with any anticoagulant during follow-up; neither of these recurrences was fatal. The incidence of recurrent VTE in all patients with MRDTI negative for DVT was 1.1% (95% CI, 0.13%-3.8%). The agreement between initial local and post hoc central reading of the MRDTI images was excellent (κ statistic, 0.91). The incidence of VTE recurrence after negative MRDTI was low, and MRDTI proved to be a feasible and reproducible diagnostic test. This trial was registered at www.clinicaltrials.gov as #NCT02262052.
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http://dx.doi.org/10.1182/blood.2019004114DOI Listing
April 2020

[Diagnostic challenge in a man with intractable hiccups and vomiting: a case of neuromyelitis optica spectrum disorder (NMOSD)].

Lakartidningen 2019 Aug 13;116. Epub 2019 Aug 13.

Danderyds sjukhus - Röntgenavd Stockholm, Sweden Danderyds sjukhus - Röntgenavd Stockholm, Sweden.

Neuromyelitis optica is an inflammatory CNS syndrome that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). According to the new diagnostic criteria the term NMO is replaced by the term NMOSD and for the first time criteria allow diagnosis in patients who have not experienced clinical involvement of either optic nerves or spinal cord. Area postrema, the emetic reflex center, may be a selective target of the disease. We report a case of a 74-year-old man who presented with intractable hiccups and vomiting. He underwent medical and surgical evaluation but the neurological consultation was delayed one month because these symptoms are usually not appreciated as the possible initial manifestation of NMOSD. Missing diagnosis at this early stage leads to a delay in the treatment and a risk of more severe manifestations, such as transverse myelitis.
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August 2019

Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke.

Neurology 2018 11 26;91(22):e2067-e2077. Epub 2018 Oct 26.

From Edinburgh Imaging, and UK Dementia Research Institute at the University of Edinburgh and Centre for Clinical Brain Sciences (G.M., Z.M., A.J.F., J.M.W.), and Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Medicine (L.C.), University of Western Australia; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Department of Neurology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy; Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.

Objective: To determine whether alteplase alters the development of ischemic lesions on brain imaging after stroke.

Methods: The Third International Stroke Trial (IST-3) was a randomized controlled trial of IV alteplase for ischemic stroke. We assessed CT or brain MRI at baseline (pretreatment) and 24 to 48 hours posttreatment for acute lesion visibility, extent, and swelling, masked to all other data. We analyzed associations between treatment allocation, change in brain tissue appearances between baseline and follow-up imaging, and 6-month functional outcome in IST-3. We performed a meta-analysis of randomized trials of alteplase vs control with pre- and postrandomization imaging.

Results: Of 3,035 patients recruited in IST-3, 2,916 had baseline and follow-up brain imaging. Progression in either lesion extent or swelling independently predicted poorer 6-month outcome (adjusted odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.88-0.96, < 0.001; OR = 0.73, 95% CI 0.66-0.79, < 0.001, respectively). Patients allocated alteplase were less likely than controls to develop increased lesion visibility at follow-up (OR = 0.77, 95% CI 0.67-0.89, < 0.001), but there was no evidence that alteplase reduced progression of lesion extent or swelling. In meta-analysis of 6 trials including IST-3 (n = 4,757), allocation to alteplase was associated with a reduction in ischemic lesion extent on follow-up imaging (OR = 0.85, 95% CI 0.76-0.95, = 0.004).

Conclusion: Alteplase was associated with reduced short-term progression in lesion visibility. In meta-analysis, alteplase reduced lesion extent. These findings may indicate that alteplase improves functional outcome by reducing tissue damage.

Classification Of Evidence: This study provides Class II evidence that IV alteplase impedes the progression of ischemic brain lesions on imaging after stroke.
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http://dx.doi.org/10.1212/WNL.0000000000006575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282236PMC
November 2018

[Unnecessary tests].

Lakartidningen 2017 11 14;114. Epub 2017 Nov 14.

Danderyds sjukhus - Röntgenavd Stockholm, Sweden Danderyds sjukhus - Röntgenavd Stockholm, Sweden.

Unnecessary tests Medical and technological development can make tests obsolete. Radiological exams of the lumbar spine only rarely adds value for the patient. Follow validated guidelines in order to decide when, and how, to perform imaging of the lumbar spine.
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November 2017

Blood pressure variability and leukoaraiosis in acute ischemic stroke.

Int J Stroke 2018 07 5;13(5):473-480. Epub 2017 Sep 5.

2 Brain Research Imaging Centre, The University of Edinburgh, Edinburgh, UK.

Higher blood pressure, blood pressure variability, and leukoaraiosis are risk factors for early adverse events and poor functional outcome after ischemic stroke, but prior studies differed on whether leukoaraiosis was associated with blood pressure variability, including in ischemic stroke. In the Third International Stroke Trial, blood pressure was measured in the acute phase of ischemic stroke immediately prior to randomization, and at 0.5, 1, and 24 h after randomization. Masked neuroradiologists rated index infarct, leukoaraiosis, and atrophy on CT using validated methods. We characterized blood pressure variation by coefficient of variance and three other standard methods. We measured associations between blood pressure, blood pressure variability, and leukoaraiosis using generalized estimating equations, adjusting for age, and a number of covariates related to treatment and stroke type/severity. Among 3017 patients, mean (±SD) systolic and diastolic blood pressure decreased from 155(±24)/82(±15) mmHg pre-randomization to 146(±23)/78(±14) mmHg 24 h later ( P < 0.005). Mean within-subject coefficient of variance was 0.09 ± 0.05 for systolic and 0.11 ± 0.06 for diastolic blood pressure. Patients with most leukoaraiosis were older and had higher blood pressure than those with least ( P < 0.0001). Although statistically significant in simple pairwise comparisons, no measures of blood pressure variability were associated with leukoaraiosis when adjusting for confounding variables ( P > 0.05), e.g. age. Our results suggest that blood pressure variability is not a potential mechanism to explain the association between leukoaraiosis and poor outcome after acute stroke.
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http://dx.doi.org/10.1177/1747493017729267DOI Listing
July 2018

[Encefalopathy as a side effect of metronidazole therapy – a case report].

Lakartidningen 2017 03 20;114. Epub 2017 Mar 20.

Strokeenh, Medicinkliniken, Danderyds sjh - Stockholm, Sweden.

Encefalopathy as a side effect of metronidazole therapy - a case report  Neurological symptoms as side effects of pharmacological treatment generally tend to remain underdiagnosed. In this report, we present a case of a 79 year old patient that developed encephalopathy whilst undergoing prophylactic treatment with Metronidazole. The initial presentation of disseminated neurological symptoms lead to the suspicion of a cerebrovascular lesion. However, exacerbation of symptomatology with gait disturbance, ataxia and dysarthria challenged the preliminary diagnosis. Brain magnetic resonance imaging (MRI) demonstrated T2 hyper-intensity over bilateral dentate nuclei. A drug history revealed that the patient had been treated with Metronidazole daily for several weeks due to a surgical condition. Cessation of the drug provided reversal of symptoms and radiological findings upon follow up MRI. This case report aims at increasing awareness regarding side effects of Metronidazole as well as early detection in patients who present with neurological symptoms.
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March 2017

[Diagnostic errors are prevalent and hard to measure].

Lakartidningen 2017 03 13;114. Epub 2017 Mar 13.

Danderyds sjukhus - Röntgenavd Stockholm, Sweden Danderyds sjukhus - Röntgenavd Stockholm, Sweden.

Diagnostic errors are prevalent and hard to measure Diagnostic errors are prevalent in all aspects of healthcare and a common cause of adverse events. They are often the result of multifactorial events, where there is a complex interplay between cognitive factors, system factors and lack of adequate knowledge. The generic, iterative diagnostic process, with abductive, deductive and inductive components supported by tests and the physical exam, leads to a correct diagnosis for the great majority of patients, but can be derailed by suboptimal thinking, lack of adequate information and external factors such as stress and work overload. The cognitive sciences have much to teach us about dual process theory and cognitive biases. Education, systematic feedback, lifelong learning, multidisciplinary diagnostic teams and integrated decision support are possible remedies. It is imperative that validated methods of measuring diagnostic errors and common terminologies are developed. When a diagnostic error is identified, robust routines are essential to minimise patient harm.
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March 2017

[Swedish consensus statement for the use of MRI in MS].

Lakartidningen 2017 02 27;114. Epub 2017 Feb 27.

Danderyds sjukhus - Röntgenavd Stockholm, Sweden Danderyds sjukhus - Röntgenavd Stockholm, Sweden.

Swedish consensus statement for the use of MRI in MS Despite the importance of MRI in the follow-up of MS, there is currently insufficient evidence to clearly define how it should be utilised in the clinical care of individuals with MS. The Swedish Multiple Sclerosis Association together with the Swedish Neuroradiological Society here present a consensus-based document that gives recommendations on several important aspects of clinical use of MRI for MS.
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February 2017

NETosis promotes cancer-associated arterial microthrombosis presenting as ischemic stroke with troponin elevation.

Thromb Res 2016 Mar 12;139:56-64. Epub 2016 Jan 12.

Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden.

Introduction: Large elevations of high sensitive Troponin T (hsTnT) in ischemic stroke patients is associated with a poor outcome. In a pilot study we found a high prevalence of malignancies among these patients. Since neutrophil extracellular traps (NETs) have been linked to cancer-associated thrombosis, we hypothesized that the concomitant cerebral and myocardial ischemia could be the result of a NET-induced hypercoagulable state.

Materials And Methods: Clinical assessments, plasma analyses and autopsies with histopathology (in cases of in-hospital mortality) were performed on ischemic stroke patients with high elevations of hsTnT (N=12) and normal hsTnT (N=19).

Results: Patients with hsTnT elevation had an unexpectedly higher prevalence of cancer (p=0.002), half of which were diagnosed post-mortem. Autopsies of these patients revealed widespread myocardial, cerebral and pulmonary microthrombosis with H3Cit in thrombi. A pro-coagulant state and an increase of the NET specific marker citrullinated histone H3 (H3Cit) was found in plasma of patients with elevated hsTnT compared to patients with normal levels (p<0.001). Plasma analyses in cancer patients showed even higher H3Cit levels (p<0.001), and an increase in granulocyte colony-stimulating factor, known to prime neutrophils towards NETosis. H3Cit correlated positively with thrombin-antithrombin complex (p=0.004) and soluble P-selectin (p<0.001), further linking NETosis to the pro-thrombotic state.

Conclusions: The high prevalence of known or occult cancer in our study suggests that cancer-associated arterial microthrombosis may be underestimated. By linking the thrombosis to NETs, we suggest markers of NETosis that could aid in revealing cancer in arterial microthrombosis as well as arterial microthrombosis in cancer.
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http://dx.doi.org/10.1016/j.thromres.2016.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769435PMC
March 2016

Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke.

Neurology 2016 Jan 9;86(2):118-25. Epub 2015 Dec 9.

From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.

Objective: To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3).

Methods: All prerandomization and follow-up (24-48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518).

Results: HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167).

Conclusions: IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS.

Classification Of Evidence: This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.
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http://dx.doi.org/10.1212/WNL.0000000000002236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731690PMC
January 2016

[Diagnostic errors is a new focus in the IOM report. Diagnostics needs more attention in the work with patient safety].

Lakartidningen 2015 Dec 7;112. Epub 2015 Dec 7.

- Bromma, Sweden - Bromma, Sweden.

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December 2015

Similar results comparing early and late surgery in open repair of traumatic rotator cuff tears.

Knee Surg Sports Traumatol Arthrosc 2016 Dec 12;24(12):3899-3906. Epub 2015 Nov 12.

Division of Orthopaedics, Danderyds University Hospital, Denderyd, Sweden.

Purpose: The purpose was to investigate whether surgical repair earlier or later than 3 months after injury may result in similar outcomes and patient satisfaction.

Methods: Seventy-three patients (75 shoulders, 58 males, mean age 59) who had undergone surgical intervention for traumatic rotator cuff tears from 1999 to 2011 were assessed by MRI, clinical examination and Western Ontario Rotator Cuff Index (WORC) as a primary outcome measure and Oxford Shoulder score (OSS), Constant-Murley score (CS) and EQ-5D as secondary. The patients treated less than 3 months after injury (n = 39) were compared with patients treated more than 3 months after injury (n = 36). The average follow-up time was 56 months (range 14-149), and the average time from injury to repair for all patients was 16 weeks (range 3-104). A single senior radiologist performed a blinded evaluation of all the MRIs. Rotator cuff integrity, presence of arthritis, fatty degeneration and muscle atrophy were evaluated.

Results: No differences were found for any of the assessed outcomes (WORC, OSS, CS and EQ-5D) between the two groups. The mean WORC % was 77 % for both groups. Re-tear frequency was 24 %, nine in both groups. Patients with re-tear reported less satisfaction with their outcome.

Conclusions: The surgical treatment of symptomatic traumatic rotator cuff tears repairable later than 3 months after injury yields a good functional outcome, a high level of subjective patient satisfaction, and at the same level for patients receiving earlier treatment. Based on our findings, surgical repair could be encouraged whenever technically possible.

Level Of Evidence: Retrospective Comparative Study, Level III.
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http://dx.doi.org/10.1007/s00167-015-3840-0DOI Listing
December 2016

A case of posterior reversible encephalopathy syndrome associated with gilenya(®) (fingolimod) treatment for multiple sclerosis.

Front Neurol 2015 4;6:39. Epub 2015 Mar 4.

Department of Radiology, Danderyd Hospital , Danderyd , Sweden.

We describe posterior reversible encephalopathy syndrome (PRES) in a woman with multiple sclerosis treated with Gilenya(®) (Fingolimod). The first symptoms appeared after 21 months of fingolimod treatment. She experienced headache, altered mental status, cognitive deficits, seizures, and visual disturbances. Not at any time during the course of the disease could any signs of infection or rheumatic disorder be detected. Test for anti-neuronal antibodies was also negative. Her blood pressure was normal. MRI showed widespread cortical and subcortical changes with some mass-effect in the temporo-occipital-parietal lobes in the left hemisphere. Contrast enhancement was seen in the leptomeninges and, in addition, there were no areas with restricted diffusion and no signs of hemorrhage. Her condition deteriorated until fingolimod was discontinued. Slowly her condition improved and after 8 months, the only symptoms that remained were two small, non-corresponding, right inferior scotomas. We believe that all symptoms, the clinical course, and the MRI findings in this case can all be explained by considering PRES, a probably rare, but serious, side effect of fingolimod treatment.
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http://dx.doi.org/10.3389/fneur.2015.00039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349179PMC
March 2015

Clinical and radiological findings in methadone-induced delayed leukoencephalopathy.

J Rehabil Med 2014 Sep;46(8):828-30

Department of Rehabilitation Medicine, Institution of Clinical Sciences, Karolinska Institutet, 182 88 Stockholm, Sweden.

Objective: To increase awareness of the incidence of delayed leukoencephalopathy in rehabilitation medicine.

Subject: A 34-year-old male patient in an inpatient neuro-rehabilitation clinic who developed cognitive, psychological and physical deterioration 33 days after methadone intake.

Methods: Clinical follow-up for 7 months, brain imaging with magnetic resonance imaging and computed tomography, electroencephalography, multidisciplinary team evaluation and rehabilitation, pharmacological treatment, and examination of medical records.

Results: Clinical findings showed neuropsychological and motor deterioration. Brain images demonstrated that previous white matter infarctions had developed to cystic substance defects, and that abnormally high signals developed in the white matter of most cerebral lobes, with the exception of the grey matter and the cerebellum. Clinical improvement coincided with a modification in pharmacological treatment (increase in sertraline and introduction of baclofen). Brain images at 3 and 6 months after the methadone overdose showed reduced intensity of signal abnormalities and complete normalization of diffusion weighted images. Evaluation 7 months after injury estimated moderate brain injury with moderate disability and partial recovery of the patient's capacity for previous activities of daily living.

Conclusion: Delayed leukoencephalopathy should be suspected in patients who deteriorate after methadone overdose. Drugs such as sertraline and baclofen may be of use in treating delayed leukoencephalopathy.
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http://dx.doi.org/10.2340/16501977-1820DOI Listing
September 2014

Trousseau's Syndrome, a Previously Unrecognized Condition in Acute Ischemic Stroke Associated With Myocardial Injury.

J Investig Med High Impact Case Rep 2014 Apr-Jun;2(2):2324709614539283. Epub 2014 Jun 24.

Karolinska Institutet, Dept of Clinical Sciences, Division of Cardiovascular Medicine, Danderyd Hospital, Stockholm, Sweden.

Trousseau's syndrome is a well-known malignancy associated hypercoagulative state leading to venous or arterial thrombosis. The pathophysiology is however poorly understood, although multiple mechanisms are believed to be involved. We report a case of Trousseau's syndrome resulting in concomitant cerebral and myocardial microthrombosis, presenting with acute ischemic stroke and markedly elevated plasma troponin T levels suggesting myocardial injury. Without any previous medical history, the patient developed multiple cerebral infarctions and died within 11 days of admission. The patient was postmortem diagnosed with an advanced metastatic adenocarcinoma of the prostate with disseminated cerebral, pulmonary, and myocardial microthrombosis. Further analyses revealed, to the best of our knowledge for the first time in stroke patients, circulating microvesicles positive for the epithelial tumor marker CK18 and citrullinated histone H3 in thrombi, markers of the recently described cancer-associated procoagulant DNA-based neutrophil extracellular traps. We also found tissue factor, the main in vivo initiator of coagulation, both in thrombi and in metastases. Troponin elevation in acute ischemic stroke is common and has repeatedly been associated with an increased risk of mortality. The underlying pathophysiology is however not fully clarified, although a number of possible explanations have been proposed. We now suggest that unexplainable high levels of troponin in acute ischemic stroke deserve special attention in terms of possible occult malignancy.
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http://dx.doi.org/10.1177/2324709614539283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528894PMC
October 2015

Presymptomatic diagnosis with MRI and adequate treatment ameliorate the outcome after natalizumab-associated progressive multifocal leukoencephalopathy.

Front Neurol 2013 18;4:11. Epub 2013 Feb 18.

Neurology Unit, Division of Internal Medicine, Danderyd Hospital, Karolinska Institutet Stockholm, Sweden.

Natalizumab (Tysabri(®)) is a monoclonal antibody that prevents inflammatory cells from binding to brain endothelial cells and passing into the brain parenchyma. Natalizumab is a highly effective treatment for relapsing-remitting multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain JC virus infection that has been shown to be associated with natalizumab treatment. We describe PML in a patient with MS after 44 monthly infusions of natalizumab. With the aid of a routine Magnetic resonance imaging (MRI) scan, PML was detected before any unambiguous clinical manifestations had emerged. PML was treated with plasma exchange to accelerate removal of natalizumab. Mirtazapine and mefloquine was promptly added and approximately 1 month after plasma exchange, when an immune-reconstitution-inflammatory-syndrome appeared, steroid treatment was initiated. Steroid treatment was then continued until no virus could be detected in the cerebrospinal fluid. The outcome was favorable. We believe that this case clearly illustrates the importance of an early, presymptomatic, detection of PML, and an adequate treatment. We also propose that surveillance with MRI scans, every 3 months after 24 months of treatment, should be performed in JC virus antibody positive natalizumab-treated MS patients in order to detect PML in an early phase.
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http://dx.doi.org/10.3389/fneur.2013.00011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575071PMC
February 2013

Cancer and diverticulitis of the sigmoid colon. Differentiation with computed tomography versus magnetic resonance imaging: preliminary experiences.

Acta Radiol 2013 Apr 14;54(3):237-41. Epub 2013 Jan 14.

Department of Clinical Sciences, Division of Surgery, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.

Background: Both colon cancer and diverticular disease are common in the Western world. A challenge when patients present with clinical findings is that both diseases can present with symptoms that may mimic the other.

Purpose: To determine whether magnetic resonance imaging (MRI) could be helpful to differentiate between diverticulitis and cancer of the sigmoid colon compared to the differentiation offered by evaluation of multidetector computed tomography (CT) in a clinical situation.

Material And Methods: Thirty patients were consecutively included. Fifteen patients were under work-up for a recently diagnosed sigmoid cancer and 15 patients had recently been treated in hospital due to first-time acute sigmoid diverticulitis. All patients underwent CT, T2- weighted MRI and diffusion-weighted MRI. Anonymized examinations were retrospectively presented in random order to one experienced radiologist.

Results: With contrast-enhanced CT, the sensitivity and specificity for diagnosis of cancer and diverticulitis were 66.7% (10/15) and 93.3% (14/15), respectively. Using T2-weighted and diffusion-weighted MR images, the sensitivity and specificity for diagnosis of cancer and diverticulitis were 100% (14/14) and 100% (14/14), respectively.

Conclusion: MRI provides information that may contribute to improve the differentiation between sigmoid cancer and diverticulitis that is offered by CT. These encouraging results need to be confirmed in a larger study.
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http://dx.doi.org/10.1258/ar.2012.120543DOI Listing
April 2013

Progressive multifocal leukoencephalopathy after natalizumab monotherapy.

N Engl J Med 2009 Sep;361(11):1081-7

Neurology Unit, Division of Internal Medicine, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.

We describe progressive multifocal leukoencephalopathy (PML) caused by infection with human polyomavirus JC virus in a patient with multiple sclerosis who was treated with natalizumab. The first PML symptoms appeared after 14 monthly infusions of the drug. Magnetic resonance imaging (MRI) showed a presumed multiple sclerosis lesion, and JC virus DNA was not detected on polymerase-chain-reaction (PCR) assay of cerebrospinal fluid. The patient's symptoms worsened, and the diagnosis of PML was established with a more sensitive quantitative PCR assay after 16 infusions of natalizumab. Plasma exchange was used to accelerate clearance of natalizumab. Approximately 3 weeks after plasma exchange, an immune-reconstitution inflammatory syndrome appeared. JC virus DNA was no longer detectable on quantitative PCR assay, and the patient's symptoms improved.
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http://dx.doi.org/10.1056/NEJMoa0810316DOI Listing
September 2009