Publications by authors named "Jan Purrucker"

62 Publications

Diagnostic Accuracy in Teleneurological Stroke Consultations.

J Clin Med 2021 Mar 11;10(6). Epub 2021 Mar 11.

Department of Neurology, Heidelberg University Hospital, 69120 Heidelberg, Germany.

Background: The accuracy of diagnosing acute cerebrovascular disease via a teleneurology service and the characteristics of misdiagnosed patients are insufficiently known.

Methods: A random sample ( = 1500) of all teleneurological consultations conducted between July 2015 and December 2017 was screened. Teleneurological diagnosis and hospital discharge diagnosis were compared. Diagnoses were then grouped into two main categories: cerebrovascular disease (CVD) and noncerebrovascular disease. Test characteristics were calculated.

Results: Out of 1078 consultations, 52% ( = 561) had a final diagnosis of CVD. Patients with CVD could be accurately identified via teleneurological consultation (sensitivity 95.2%, 95% CI 93.2-96.8), but we observed a tendency towards false-positive diagnosis (specificity 77.4%, 95% CI 73.6-80.8). Characteristics of patients with a false-negative CVD diagnosis were similar to those of patients with a true-positive diagnosis, but patients with a false-negative CVD diagnosis had ischemic heart disease less frequently. In retrospect, one patient would have been considered a candidate for intravenous thrombolysis (0.2%).

Conclusions: Teleneurological consultations are accurate for identifying patients with CVD, and there is a very low rate of missed candidates for thrombolysis. Apart from a lower prevalence of ischemic heart disease, characteristics of "stroke chameleons" were similar to those of correctly identified CVD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10061170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998723PMC
March 2021

[Neurovascular manifestations of COVID‑19].

Nervenarzt 2021 Mar 24. Epub 2021 Mar 24.

Neurologische Klinik, Alfried Krupp Krankenhaus Essen, Alfried Krupp Str. 21, 45131, Essen, Deutschland.

Even early at the beginning of the coronavirus disease 2019 (COVID‑19) pandemic, stroke was described as a manifestation or complication of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current meta-analyses reported a stroke rate of approximately 1.5%. Stroke in COVID‑19 positive patients occurs more frequently in severe courses of the infection and in older patients with cardiovascular comorbidities; however, young patients without cardiovascular risk factors are also not uncommonly affected. The mechanisms of stroke are predominantly embolic. The thrombi frequently occlude large intracranial vessels and in more than 20% affect multiple vascular territories, whereas infarctions due to small vessel disease are uncommon. The exact source of the embolism remains cryptogenic in more than 40% of patients. The mortality caused by the co-occurrence of a SARS-CoV‑2 infection and a stroke exceeds 15-30%. While acute stroke treatment was severely affected in some European regions, the rates of recanalization treatment in Germany largely remained stable during the first pandemic wave; however, 20-30% fewer patients with minor stroke and transient ischemic attacks (TIA) presented to hospitals during the first wave in spring 2020. The present narrative review summarizes the current evidence regarding the epidemiology and pathogenesis of stroke associated with COVID‑19 and describes the effect of the pandemic so far on the provision of acute stroke treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00115-021-01104-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990492PMC
March 2021

Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Lancet Neurol 2021 04 17;20(4):294-303. Epub 2021 Mar 17.

Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Background: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk.

Methods: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602.

Findings: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models.

Interpretation: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted.

Funding: British Heart Foundation and Stroke Association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1474-4422(21)00024-7DOI Listing
April 2021

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

High Alt Med Biol 2021 Mar 11;22(1):87-89. Epub 2021 Mar 11.

1st Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.

Speidel, Victor, Jan Christoph Purrucker, and Katarína Klobučníková. Manifestation of intracranial lesions at high altitude: case report and review of the literature. . 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/ham.2020.0223DOI Listing
March 2021

Age-Dependent Differences in the Rate and Symptoms of TIA Mimics in Patients Presenting With a Suspected TIA to a Neurological Emergency Room.

Front Neurol 2021 15;12:644223. Epub 2021 Feb 15.

Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.

Transient ischemic attack (TIA) needs further diagnostic evaluation to prevent future ischemic stroke. However, prophylaxis can be harmful in elderly if the diagnosis is wrong. We aimed at characterizing differences in TIA mimics in younger and older patients to enhance diagnostic accuracy in elderly patients. In a dedicated neurological emergency room (nER) of a tertiary care University hospital, patients with transient neurological symptoms suspicious of TIA (<24 h) were retrospectively analyzed regarding their final diagnoses and their symptoms. These parameters were compared between patients aged 18-70 and >70 years using descriptive, univariable, and multivariable statistics. From November 2018 until August 2019, 386 consecutive patients were included. 271 (70%) had cardiovascular risk factors and all patients received cerebral imaging, mostly CT [376 (97%)]. There was no difference in the rate of diagnosed TIA between the age groups [85 (46%) vs. 58 (39%); = 0.213].TIA mimics in the elderly were more often internal medicine diseases [35 (19%) vs. 7 (5%); < 0.001] and epileptic seizures [48 (26%) vs. 24 (16%); = 0.032] but less often migraine [2 (1%) vs. 20 (13%); < 0.001]. The most frequent symptoms in all patients were aphasia and dysarthria [107 (28%) and 92 (24%)]. Sensory impairments were less frequent in elderly patients [23 (11%) vs. 54 (30%); < 0.001]. Impaired consciousness and orientation were independent predictors for TIA mimics ( < 0.001) whereas facial palsy ( < 0.001) motor weakness ( < 0.001), dysarthria ( = 0.022) and sensory impairment ( < 0.001) were independent predictors of TIA. TIA mimics in elderly patients are more likely to be internal medicine diseases and epilepsy compared to younger patients. Excluding internal medicine diseases seems to be important in elderly patients. Facial palsy, motor weakness, dysarthria and sensory impairment are associated with TIA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.644223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917180PMC
February 2021

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

J Neurol Neurosurg Psychiatry 2021 May 4;92(5):534-541. Epub 2021 Feb 4.

Neurology, Christchurch Hospital, Christchurch, New Zealand.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2020-325456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053326PMC
May 2021

Differential effects of the SARS-CoV-2 pandemic on patients presenting to a neurological emergency room depending on their triage score in an area with low COVID-19 incidence.

Eur J Neurol 2020 Dec 29. Epub 2020 Dec 29.

Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.

Background: We analyzed the effects of the SARS-CoV-2 pandemic on neurologic emergencies, depending on the patients' triage score in a setting with relatively few COVID-19 cases and without lack of resources.

Methods: Consecutive patients of a tertiary care center with a dedicated neurologic emergency room (nER) were analyzed. The time period of the first lockdown in Germany (calendar weeks 12-17, 2020) was retrospectively compared to the corresponding period in 2019 regarding the number of patients presenting to the nER, the number of patients with specific triage scores (Heidelberg Neurological Triage Score), the number of patients with stroke, and the quality of stroke care.

Results: A total of 4330 patients were included. Fewer patients presented themselves in 2020 compared to 2019 (median [interquartile range] per week: 134 [118-143] vs. 187 [182-192]; p = 0.015). The median numbers of patients per week with triage 1 (emergent) and 4 (non-urgent) were comparable (51 [43-58] vs. 59 [54-62]; p = 0.132, and 10 [4-16] vs. 16 [7-18]; p = 0.310, respectively).The median number of patients per week declined in categories 2 and 3 in 2020 (41 [37-45] vs. 57 [52-61]; p = 0.004, and 28 [23-35] vs. 61 [52-63]; p = 0.002, respectively. No change was observed in the absolute number of strokes (138 in 2019 and 141 in 2020). Quality metrics of stroke revascularization therapies (symptom-to-door time, door-to-needle time or relative number of therapies) and stroke severity remained constant.

Conclusion: During the lockdown period in 2020, the number of patients with emergent symptoms remained constant, while fewer patients with urgent symptoms presented to the nER. This may imply behavioral changes in care-seeking behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ene.14709DOI Listing
December 2020

Real-world outcomes in non-endemic hereditary transthyretin amyloidosis with polyneuropathy: a 20-year German single-referral centre experience.

Amyloid 2021 Jun 7;28(2):91-99. Epub 2020 Dec 7.

Amyloidosis Center, Heidelberg University Hospital, Heidelberg, Germany.

Background: Hereditary transthyretin amyloidosis is caused by pathogenic variants in the gene and typically manifests, alongside cardiac and other organ dysfunctions, with a rapidly progressive sensorimotor and autonomic polyneuropathy (ATTRv-PN) leading to severe disability. While most prospective studies have focussed on endemic ATTRv-PN, real-world data on non-endemic, mostly late-onset ATTRv-PN are limited.

Methods: This retrospective study investigated ATTRv-PN patients treated at the Amyloidosis Centre of Heidelberg University Hospital between November 1999 and July 2020. Clinical symptoms, survival, prognostic factors and efficacy of treatment with tafamidis were analysed. Neurologic outcome was assessed using the Coutinho ATTRv-PN stages, and the Peripheral Neuropathy Disability (PND) score.

Results: Of 346 subjects with genetic variants, 168 patients had symptomatic ATTRv-PN with 32 different TTR variants identified. Of these, 81.6% had the late-onset type of ATTRv-PN. Within a mean follow-up period of 4.1 ± 2.8 years, 40.5% of patients died. Baseline plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) ≥900 ng/l (HR 3.259 [1.421-7.476];  = .005) was the main predictor of mortality in multivariable analysis. 64 patients were treated with tafamidis and presented for regular follow-up examinations. The therapeutic benefit of tafamidis was more pronounced when treatment was started early in ATTRv-PN stage 1 (PND scores II vs. I; HR 2.718 [1.258-5.873];  = .011).

Conclusions: In non-endemic, mostly late-onset ATTRv-PN, cardiac involvement assessed by NT-proBNP is a strong prognosticator for overall survival. Long-term treatment with tafamidis is safe and efficacious. Neurologic disease severity at the start of treatment is the main predictor for ATTRv-PN progression on tafamidis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13506129.2020.1855134DOI Listing
June 2021

Design and Derivation of the Austrian Prehospital Stroke Scale (APSS) to Predict Severe Stroke with Large Vessel Occlusion.

Prehosp Emerg Care 2021 Jan 12:1-9. Epub 2021 Jan 12.

Prediction of large vessel occlusion (LVO) is highly relevant for accurate prehospital transportation triage. The Austrian Prehospital Stroke Scale (APSS) score for LVO prediction was developed using critical synthesis of previously published LVO-scores. The aim of this study was to investigate the accuracy of the APSS and compare it to other LVO-scores. APSS consists of 5 items: "facial palsy," "motor arm," "language," "motor leg" and "gaze deviation." The score ranges from 0 to 9 points. Data from 741 consecutive stroke patients with acute vessel imaging admitted to an independent comprehensive stroke center was used to test the predictive performance of the APSS in context of other LVO-scores (CPSS, FAST-ED, G-FAST, sNIHSS-EMS and RACE). In the prediction of treatable LVO the APSS showed the highest area under the curve (0.834) with significant difference to CPSS (p = 0.010) and G-FAST (p = 0.006) and showed highest sensitivity (69%) as compared to other LVO scores. Specificity (85%), positive predictive value (75%), negative predictive value (81%) and accuracy (79%) were comparable to other LVO scores. Receiver operating curve analysis revealed an optimal cutoff for LVO prediction at APSS equal to 4 points. The easy assessable 5-item APSS score tended to outperform other LVO scores. Real-life prospective evaluation in prehospital setting is ongoing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10903127.2020.1851329DOI Listing
January 2021

Patient profiles contribute to differences in quality metrics of stroke centers.

Neurosciences (Riyadh) 2020 Aug;25(4):292-300

Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.

Objective: To examine this association by comparing patient profiles in 2 closely affiliated hospitals and by examining their association with quality metrics.

Methods: We performed a retrospective cohort study comparing a university level comprehensive stroke centers (CSC) with its teaching hospital and local stroke unit (LSU) using routinely collected quality assurance data over a 2 year period. Both hospitals were closely affiliated, shared important resources and medical staff rotated amongst both hospitals. We compared patient profiles as well as internationally recognized quality metrics and examined the association of profiles with quality metrics.

Results: A total of 2,462 patients were treated in the CSC and 726 in the LSU. The LSU had a longer door-to-image and door-to-needle times. Rate of systemic thrombolysis was lower in the LSU. Patient profiles differed significantly and were associated with door-to-image and door-to-needle times as well as intravenous thrombolysis rates, even when adjusted for stroke service level. The diagnostic procedures for stroke work-up were similar. Discharge management differed strongly.

Conclusion: Although LSUs and CSCs are the primary care providers in their respective regions, differences in patient profiles may contribute to differences in performance parameters. Adjusting for patient profiles may improve the comparability of the quality of stroke care provided by hospitals belonging to different stroke service levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17712/nsj.2020.4.20190100DOI Listing
August 2020

Etiology of Ischemic Strokes of Patients with Atrial Fibrillation and Therapy with Anticoagulants.

J Clin Med 2020 Sep 11;9(9). Epub 2020 Sep 11.

Department of Neurology, Heidelberg University Hospital, 69120 Heidelberg, Germany.

Background: Reducing the number of ischemic strokes in patients with atrial fibrillation despite oral anticoagulation remains an important, yet largely unsolved challenge. Therefore, we assessed the etiology of ischemic strokes despite anticoagulation with vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs).

Methods: Patients with known atrial fibrillation (AF), treatment with VKA or NOAC, and acute ischemic stroke admitted between 2015 and 2018 (1st half) were identified from the hospital database. Brain imaging data were independently reviewed. An integrated etiologic classification according to the ASCOD system was made. Medication errors (admission INR <2.0 in the VKA- or NOAC-specific concentration <10 ng/mL) or dosage/dosing errors were also analyzed.

Results: Of 3610 patients screened, = 341 were included (VKA, = 127; NOAC, = 214). An overall increasing rate of OAC-associated stroke per year was observed. In 95.3% of patients with adequate diagnostic work-up ( = 321/337), at least one additional potential, uncertain, or unlikely non-cardiac cause of stroke was identified. More patients in the VKA than in the NOAC group had a medication error (81/127, 63.8% vs. 102/205, 49.8%; = 0.013).

Conclusions: Stroke risk factors despite atrial fibrillation were highly prevalent. Although less common with NOACs than VKAs, medication errors are still frequent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9092938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564370PMC
September 2020

Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis.

Ann Clin Transl Neurol 2020 05 25;7(5):799-807. Epub 2020 Apr 25.

Amyloidosis Center Heidelberg, Heidelberg University Hospital, Heidelberg, Germany.

Objective: To quantify peripheral nerve lesions in symptomatic and asymptomatic hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PNP) by analyzing the magnetization transfer ratio (MTR) of the sciatic nerve, and to test its potential as a novel biomarker for macromolecular changes.

Methods: Twenty-five patients with symptomatic ATTRv-PNP, 30 asymptomatic carriers of the mutant transthyretin gene (mutTTR), and 20 age-/sex-matched healthy controls prospectively underwent magnetization transfer contrast imaging at 3 Tesla. Two axial three-dimensional gradient echo sequences with and without an off-resonance saturation rapid frequency pulse were conducted at the right distal thigh. Sciatic nerve regions of interest were manually drawn on 10 consecutive axial slices in the images without off-resonance saturation, and then transferred to the corresponding slices that were generated by the sequence with the off-resonance saturation pulse. Subsequently, the MTR and cross-sectional area (CSA) of the sciatic nerve were evaluated. Detailed neurologic and electrophysiologic examinations were conducted in all ATTRv-PNP patients and mutTTR-carriers.

Results: Sciatic nerve MTR and CSA reliably differentiated between ATTRv-PNP, mutTTR-carriers, and controls. MTR was lower in ATTRv-PNP (26.4 ± 0.7; P < 0.0001) and in mutTTR-carriers (32.6 ± 0.8; P = 0.0005) versus controls (39.4 ± 2.1), and was also lower in ATTRv-PNP versus mutTTR-carriers (P = 0.0009). MTR correlated negatively with the NIS-LL and positively with CMAPs and SNAPs. CSA was higher in ATTRv-PNP (34.3 ± 1.7 mm ) versus mutTTR-carriers (26.0 ± 1.1 mm ; P = 0.0005) and versus controls (20.4 ± 1.2 mm ; P < 0.0001). CSA was also higher in mutTTR-carriers versus controls.

Interpretation: MTR is a novel imaging marker that can quantify macromolecular changes in ATTRv-PNP and differentiate between symptomatic ATTRv-PNP and asymptomatic mutTTR-carriers and correlates with electrophysiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acn3.51049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261747PMC
May 2020

Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany-Updated series of 120 cases.

Int J Stroke 2020 Aug 19;15(6):609-618. Epub 2020 Jan 19.

Department of Neurology, University Hospital, Essen, Germany.

Background: Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth.

Aims: To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage.

Methods: Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used.

Results: One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in  = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0-3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay.

Conclusion: Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1747493019895654DOI Listing
August 2020

Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018.

Eur Stroke J 2019 Dec 2;4(4):307-317. Epub 2019 Sep 2.

Department of Neurology, Charité -- Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany. Center for Stroke Research, Charité -- Universitätsmedizin Berlin, Berlin, Germany.

The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement ( www.eso-karolinska.org http://eso-stroke.org) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2396987319863606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921948PMC
December 2019

European Stroke Organisation Guideline on Reversal of Oral Anticoagulants in Acute Intracerebral Haemorrhage.

Eur Stroke J 2019 Dec 14;4(4):294-306. Epub 2019 May 14.

Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.

The aim of the present European Stroke Organisation guideline document is to provide clinically useful evidence-based recommendation on reversal of anticoagulant activity VKA (warfarin, phenprocoumon and acenocoumarol), direct factor II (thrombin) inhibitors (dabigatran etexilat) and factor-Xa-inhibitors (apixaban, edoxaban and rivaroxaban) in patients with acute intracerebral haemorrhage. The guideline was prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined use of oral anticoagulation pragmatically: oral anticoagulation use is assumed by positive medical history unless relevant anticoagulant activity is regarded unlikely by medical history or has been ruled out by laboratory testing. Overall, we strongly recommend using prothrombin complex over no treatment and fresh-frozen plasma in patients on VKA plus vitamin K. We further strongly recommend using idarucizumab in patients on dabigatran and make a recommendation for andexanet alfa in patients on rivaroxaban and apixaban over no treatment. We make a weak recommendation on using high-dose prothrombin complex concentrate (50 IU/kg) for all patients taking edoxaban and for patients on rivaroxaban or apixaban in case andexanet alfa is not available. We recommend against using tranexamic acid and rFVIIa, outside of trials. The presented treatment recommendations aim to normalise coagulation, there is no or only indirect data on effects on functional outcome or mortality, and only little data from randomised controlled trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2396987319849763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921939PMC
December 2019

Collateral Scores in Acute Ischemic Stroke : A retrospective study assessing the suitability of collateral scores as standalone predictors of clinical outcome.

Clin Neuroradiol 2020 Dec 28;30(4):789-793. Epub 2019 Nov 28.

Department of Neuroradiology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.

Background And Purpose: Several collateral scores have been published for stroke in the middle cerebral artery territory, each considering different aspects of cerebral collateralization. Currently, there is no gold standard in CT-based collateral assessment. The aim of this retrospective study was to compare five collateral scores and determine whether they are able to predict clinical outcome after thrombectomy as standalone parameters.

Methods: Inclusion criteria were M1 occlusion, premorbid modified Rankin scale (mRS) of 0-3, treatment with endovascular thrombectomy and groin puncture within 12 h after stroke onset. The Maas et al., Miteff et al., Tan et al., ASITN/SIR and mCTA collateral scores were retrospectively assessed in multiphase CTA images and correlated with 90-day mRS (90d-mRS) scores. Good outcome was defined as 90d-mRS 0-2 or unchanged to premorbid mRS.

Results: In total, 108 patients were included of which 39.8% achieved a good outcome. The area under the curve (AUC) values of receiver operating characteristic (ROC) curve analysis for Maas et al., Miteff et al., Tan et al., ASITN/SIR and mCTA scores were 0.60 (0.51-0.70), 0.60 (0.52-0.68), 0.61 (0.51-0.70), 0.59 (0.49-0.70) and 0.61 (0.50-0.71), respectively. The correlation between 90d-mRS and Maas (r = -0.16, P = 0.091), Miteff (r = -0.25, P = 0.009), Tan (r = -0.26, P = 0.007), ASITN/SIR (r = -0.21, P = 0.030) and mCTA (r = -0.22, P = 0.021) scores was poor.

Conclusion: Although collaterals are known to correlate with clinical outcome, none of the analyzed collateral scores sufficiently predicted outcome as a standalone parameter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00062-019-00858-1DOI Listing
December 2020

Association of Surgical Hematoma Evacuation vs Conservative Treatment With Functional Outcome in Patients With Cerebellar Intracerebral Hemorrhage.

JAMA 2019 10;322(14):1392-1403

Department of Neurology, University of Cologne, Cologne, Germany.

Importance: The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established.

Objective: To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH.

Design, Setting, And Participants: Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015).

Exposure: Surgical hematoma evacuation vs conservative treatment.

Main Outcomes And Measures: The primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH.

Results: Among 578 patients with cerebellar ICH, propensity score-matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm3 vs 18.8 cm3). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], -3.7% [95% CI, -8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm3 was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume ≤12 cm3, 30.6% vs 62.3% [P = .003]; ARD, -34.7% [-38.8% to -30.6%]; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume ≥15 cm3, 74.5% vs 45.1% [P < .001]; ARD, 28.2% [95% CI, 24.6% to 31.8%]; P value for interaction, .02).

Conclusions And Relevance: Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2019.13014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784768PMC
October 2019

Unexpected excessive apixaban exposure: case report of a patient with polymorphisms of multiple apixaban elimination pathways.

BMC Pharmacol Toxicol 2019 08 29;20(1):53. Epub 2019 Aug 29.

Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

Background: Apixaban effectively lowers the risk of ischemic stroke and systemic embolism in patients with non-valvular atrial fibrillation. Systemic exposure to a given apixaban dose depends on multiple clearance pathways. Though routine quantification of direct oral anticoagulants (DOACs) in neurological emergency situations has not been widely established, suspected associations of DOAC peak concentrations with bleeding events and DOAC trough concentrations with efficacy and safety suggest that such information might support clinical decision making.

Case Presentation: We describe the case of a 75 year-old woman with atrial fibrillation maintained on apixaban who was admitted due to suspected acute stroke. Clinical work-up did not confirm ischemic or hemorrhagic stroke but routine quantification of apixaban revealed an excessively high apixaban plasma concentration (~ 3 h after the last drug intake: 1100 ng/ml (expected range: 91-321 ng/ml); ~ 12 h after drug intake: 900 ng/ml (expected range: 41-230 ng/ml)) and a substantially prolonged elimination half-life (~ 31 h). The corresponding apixaban concentration-to-dose ratio was 9900 (ng/ml)/(mg/kg/d) and 8100 (ng/ml)/(mg/kg/d), respectively (expected range: 249-463 (ng/ml)/(mg/kg/d)). Renal function was only moderately impaired (creatinine 1.36 mg/dl (0.5-1.1 mg/dl), creatinine clearance 40 ml/min). Genotype analyses revealed that the patient was a CYP3A5*3/*3 non-expressor, a heterozygous carrier of the ABCG2 c.421C/A alleles, and a homozygous carrier of ABCB1 c.2677 T/T and ABCB1 c.3435 T/T. In the absence of known drug interactions explaining apixaban clearance impairment, excessive apixaban concentrations were most probably caused by moderate renal impairment combined with multiple functional polymorphisms of apixaban clearance pathways.

Conclusions: This case suggests that concurrent genetic polymorphisms can impair multiple apixaban elimination pathways and thus substantially increase its exposure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40360-019-0331-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716843PMC
August 2019

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

J Neurointerv Surg 2020 Mar 27;12(3):252-255. Epub 2019 Jul 27.

Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.

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 =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 ( =-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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2019-015134DOI Listing
March 2020

Development and validation of the Heidelberg Neurological Triage System (HEINTS).

J Neurol 2019 Nov 18;266(11):2685-2698. Epub 2019 Jul 18.

Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.

Background/objective: Neurological syndromes are underrepresented in existing triage systems which are not validated for neurological patients; therefore, we developed and validated the new Heidelberg Neurological Triage System (HEINTS) in a prospective, single-center observational study.

Methods: Patients were triaged according to the new triage system by nurses and physicians (stage 1) as well as trained nurses (stage 2). In stage 1, all patients presenting to the neurological emergency room (ER) were triaged by nurses and physicians. In stage 2, three specially trained nurses triaged patients according to HEINTS. The main outcomes comprised interrater agreement between nurses' and physicians' triage (stage 1), sensitivity and specificity to detect emergencies (stages 1 and 2), and improvement in triage quality as a result of training (stage 2), as well as correlation of HEINTS with hospital admissions and resource utilization.

Results: In stage 1 (n = 2423 patients), sensitivity and specificity to detect neurological emergencies were 84.2% (SD 0.8%) and 85.4% (SD 0.8%) for nurses, as well as 92.4% (SD 0.6%) and 84.1% (SD 0.9%) for physicians, respectively. The interrater-reliability between nurses and physicians in stage 1 was moderate [Cohen's kappa 0.44, standard deviation (SD) 0.02]. In stage 2 (n = 506 patients), sensitivity of trained nurses increased to 94.3% (SD 1.0%), while specificity decreased to 74.8% (SD 1.9%). Correlation of HEINTS triage with hospital admission and resource utilization in both stages was highly significant.

Conclusions: HEINTS predicted hospital admissions and resource utilization. Agreement between nurses and physicians was moderate. HEINTS, applied by physicians and by nurses after training, reliably detected neurological emergencies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-019-09472-0DOI Listing
November 2019

Rationale and design of the Registry of Acute Stroke Under Novel Oral Anticoagulants-prime (RASUNOA-prime).

Eur Stroke J 2019 Jun 17;4(2):181-188. Epub 2018 Dec 17.

Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.

Background: Anticoagulation with vitamin K antagonists and non-vitamin K antagonists oral anticoagulants (NOAC) is effective in stroke prevention in patients with atrial fibrillation. However, anticoagulation also poses a major challenge for emergency treatment of patients suffering ischaemic stroke or intracerebral haemorrhage.

Aim: The registry RASUNOA-prime is designed to describe current patterns of emergency management, clinical course and outcome of patients with atrial fibrillation experiencing an acute ischaemic stroke or intracerebral haemorrhage under different anticoagulation schemes prior to stroke (NOAC, vitamin K antagonists or no anticoagulation).

Methods And Design: RASUNOA-prime (ClinicalTrials.gov, NCT02533960) is a prospective, investigator-initiated, multicentre, observational cohort study aiming to recruit 3000 patients with acute ischaemic stroke and atrial fibrillation, and 1000 patients with acute intracerebral haemorrhage and atrial fibrillation with different anticoagulation schemes pre-stroke. It is a non-interventional triple-armed study aiming at a balanced inclusion of ischaemic stroke and intracerebral haemorrhage patients according to the different anticoagulation schemes. Patients will be followed up for clinical course, management and outcome up to three months after the event. Findings in ischaemic stroke and intracerebral haemorrhage patients on NOAC will be compared with patients taking vitamin K antagonists or no anticoagulant pre-stroke.

Study Outcomes: Primary endpoint for ischaemic stroke patients: occurrence of symptomatic intracerebral haemorrhage, for intracerebral haemorrhage patients: occurrence of secondary haematoma expansion. Secondary endpoints include assessment of coagulation, use of thrombolysis and/or mechanical thrombectomy, occurrence of complications, implementation of secondary prevention.

Summary: Describing the current patterns of early management as well as outcome of stroke patients with atrial fibrillation will help guide physicians to develop recommendations for emergency treatment of stroke patients under different anticoagulation schemes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2396987318812644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591762PMC
June 2019

Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Lancet Neurol 2019 07 23;18(7):653-665. Epub 2019 May 23.

Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke.

Methods: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602.

Findings: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-1·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years).

Interpretation: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden.

Funding: British Heart Foundation and UK Stroke Association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1474-4422(19)30197-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562236PMC
July 2019

Characteristics in Non-Vitamin K Antagonist Oral Anticoagulant-Related Intracerebral Hemorrhage.

Stroke 2019 06 16;50(6):1392-1402. Epub 2019 May 16.

Department of Neurology, University of Münster, Germany (A.L.F., J.M.).

Background and Purpose- Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods- Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany. Imaging, clinical characteristics, and 3-months modified Rankin Scale (mRS) outcomes were compared in NOAC- versus VKA-related ICH patients. Propensity score matching was conducted to adjust for clinically relevant differences in baseline parameters. Subgroup analyses were performed regarding NOAC agent, dosing and present clinically relevant anticoagulatory activity (last intake <12h/24h or NOAC level >30 ng/mL). Results- Despite older age in NOAC patients, there were no relevant differences in clinical and hematoma characteristics between NOAC- and VKA-related ICH regarding baseline hematoma volume (median [interquartile range]: NOAC, 14.7 [5.1-42.3] mL versus VKA, 16.4 [5.8-40.6] mL; P=0.33), rate of hematoma expansion (NOAC, 49/146 [33.6%] versus VKA, 235/688 [34.2%]; P=0.89), and the proportion of patients with unfavorable outcome at 3 months (mRS, 4-6: NOAC 126/179 [70.4%] versus VKA 473/682 [69.4%]; P=0.79). Subgroup analyses revealed that NOAC patients with clinically relevant anticoagulatory effect had higher rates of intraventricular hemorrhage (n/N [%]: present 52/109 [47.7%] versus absent 9/35 [25.7%]; P=0.022) and hematoma expansion (present 35/90 [38.9%] versus absent 5/30 [16.7%]; P=0.040), whereas type of NOAC agent or different NOAC-dosing regimens did not result in relevant differences in imaging characteristics or outcome. Conclusions- If effectively anticoagulated, there are no differences in hematoma characteristics and functional outcome among patients with NOAC- or VKA-related ICH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03093233.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.118.023492DOI Listing
June 2019

Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage.

J Neurol Neurosurg Psychiatry 2019 07 16;90(7):783-791. Epub 2019 Apr 16.

Neurology, University of Münster, Münster, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2018-319786DOI Listing
July 2019

Prothrombin complex concentrate versus placebo, no intervention, or other interventions in critically bleeding patients associated with oral anticoagulant administration: a protocol for a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.

Syst Rev 2018 10 20;7(1):169. Epub 2018 Oct 20.

Department of Neurology, Klinikum Frankfurt Höchst, Frankfurt, Germany.

Background: Acute critical bleeding is one of the most feared complications during treatment with oral anticoagulating agents. As more patients undergo treatment with anticoagulating agents, critically bleeding episodes in patients with vitamin K antagonists, thrombin inhibitor, or factor Xa inhibitor-inducted coagulopathy will be encountered frequently by physicians. Hence, an effective treatment capable of reversing the iatrogenic coagulopathy in the acute setting is needed. In randomised clinical trials and observational studies, prothrombin complex concentrate has been reported to be superior to other acute interventions, and many guidelines recommend prothrombin complex concentrate in treatment of critically bleeding patients. The aim of this systematic review is to synthesise the evidence of the effects of prothrombin complex concentrate compared with placebo, no intervention, or other treatment options in critically bleeding patients treated with oral anticoagulants.

Methods/design: A comprehensive search for relevant published literature will be undertaken in Cochrane Central Register of Controlled Trials, MEDLINE, Embase, WHO International Clinical Trials Registry Platform, Science Citation Index, regulatory databases, and trial registers. We will include randomised clinical trials comparing prothrombin complex concentrate versus placebo, no intervention, or other interventions in critically bleeding patients with oral anticoagulant-induced coagulopathy. Data extraction and risk of bias assessment will be handled by two independent review authors. Meta-analysis will be performed as recommended by Cochrane Handbook for Systematic Reviews of Interventions, bias will be assessed with domains, and trial sequential analysis will be conducted to control random errors. Certainty will be assessed by GRADE.

Discussion: As critical bleeding in patients treated with oral anticoagulants is an increasing problem, an up-to-date systematic review evaluating the benefits and harms of prothrombin complex concentrate is urgently needed. It is the hope that this review will be able to guide best practice in treatment and clinical research of these critically bleeding patients.

Systematic Review Registration: PROSPERO CRD42018084371.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13643-018-0838-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195723PMC
October 2018

Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage.

Ann Neurol 2018 11 25;84(5):694-704. Epub 2018 Oct 25.

Department of Neurology, Christchurch Hospital, Christchurch, New Zealand.

Objective: Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain.

Methods: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension.

Results: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43).

Interpretation: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25342DOI Listing
November 2018

MR neurography biomarkers to characterize peripheral neuropathy in AL amyloidosis.

Neurology 2018 08 20;91(7):e625-e634. Epub 2018 Jul 20.

From the Department of Neuroradiology (J.K., S.H., T.H., M.P., M.B.), Amyloidosis Center Heidelberg (J.K., M.W., J.P., S.O.S., E.H., C.K., U.H.), Department of Neurology (M.W., J.P., E.H.), Division of Experimental Radiology, Department of Neuroradiology (S.H.), and Medical Department V (S.O.S., C.K., U.H.), Heidelberg University Hospital, Germany; Department of Neurology (J.M.H.), University of Michigan, Ann Arbor; and Department of Neuroradiology (M.P.), Würzburg University Hospital, Germany.

Objective: To detect, localize, and quantify peripheral nerve lesions in amyloid light chain (AL) amyloidosis by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings.

Methods: We prospectively examined 20 patients with AL-polyneuropathy (PNP) and 25 age- and sex-matched healthy volunteers. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into mild and moderate PNP. MRN in a 3.0 tesla scanner with anatomical coverage from the lumbosacral plexus and proximal thigh down to the tibiotalar joint was performed by using T2-weighted and dual-echo 2-dimensional sequences with spectral fat saturation and a 3-dimensional, T2-weighted inversion recovery sequence. Besides evaluation of nerve T2-weighted signal, detailed quantification of nerve injury by morphometric (nerve caliber) and microstructural MRN markers (proton spin density, T2 relaxation time) was conducted.

Results: Nerve T2-weighted signal increase correlated with disease severity: moderate (420.2 ± 60.1) vs mild AL-PNP (307.2 ± 17.9; = 0.0003) vs controls (207.0 ± 6.4; < 0.0001). Proton spin density was also higher in moderate (tibial: 525.5 ± 53.0; peroneal: 553.6 ± 64.5; sural: 492.0 ± 56.6) and mild AL-PNP (tibial: 431.6 ± 22.0; peroneal: 457.6 ± 21.7; sural: 404.8 ± 25.2) vs controls (tibial: 310.5 ± 14.1; peroneal: 313.6 ± 11.6; sural: 261.7 ± 11.0; < 0.0001 for all nerves). T2 relaxation time was elevated in moderate AL-PNP only (tibial: = 0.0106; peroneal: = 0.0070; sural: = 0.0190). Tibial nerve caliber was higher in moderate (58.0 ± 8.8 mm) vs mild AL-PNP (46.5 ± 2.5 mm; = 0.008) vs controls (39.1 ± 1.2 mm; < 0.0001).

Conclusions: MRN detects and quantifies peripheral nerve injury in AL-PNP in vivo with high sensitivity and in close correlation with the clinical stage. Quantitative parameters are feasible new imaging biomarkers for the detection of early AL-PNP and might help to monitor microstructural nerve tissue changes under treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000006002DOI Listing
August 2018

Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves.

Eur Heart J 2018 05;39(19):1709-1723

Department of Neurology, University of Münster, Albert-Schweitzer-Campus 1, Münster 48149, Germany.

Aims: Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH.

Methods And Results: We pooled individual patient-data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no-TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity-score matching and multivariable cox-regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no-TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no-TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate-ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67-35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA-timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33-21.37; P < 0.01). The hazard for the composite-balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10-5.70; P = 0.03).

Conclusion: Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing-between least risks for thromboembolic and haemorrhagic complications-provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehy056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5950928PMC
May 2018

Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage.

Ann Neurol 2018 01;83(1):186-196

Department of Neurology, University of Erlangen-Nuremberg, Erlangen.

Objective: To investigate parameters associated with hematoma enlargement in non-vitamin K antagonist oral anticoagulant (NOAC)-related intracerebral hemorrhage (ICH).

Methods: This retrospective cohort study includes individual patient data for 190 patients with NOAC-associated ICH over a 5-year period (2011-2015) at 19 departments of neurology across Germany. Primary outcome was the association of prothrombin complex concentrate (PCC) administration with hematoma enlargement. Subanalyses were calculated for blood pressure management and its association with the primary outcome. Secondary outcomes include associations with in-hospital mortality and functional outcome at 3 months assessed using the modified Rankin Scale.

Results: The study population for analysis of primary and secondary outcomes consisted of 146 NOAC-ICH patients with available follow-up imaging. Hematoma enlargement occurred in 49/146 (33.6%) patients with NOAC-related ICH. Parameters associated with hematoma enlargement were blood pressure ≥ 160mmHg within 4 hours and-in the case of factor Xa inhibitor ICH-anti-Xa levels on admission. PCC administration prior to follow-up imaging was not significantly associated with a reduced rate of hematoma enlargement either in overall NOAC-related ICH or in patients with factor Xa inhibitor intake (NOAC: risk ratio [RR] = 1.150, 95% confidence interval [CI] = 0.632-2.090; factor Xa inhibitor: RR = 1.057, 95% CI = 0.565-1.977), regardless of PCC dosage given or time interval until imaging or treatment. Systolic blood pressure levels < 160mmHg within 4 hours after admission were significantly associated with a reduction in the proportion of patients with hematoma enlargement (RR = 0.598, 95% CI = 0.365-0.978). PCC administration had no effect on mortality and functional outcome either at discharge or at 3 months.

Interpretation: In contrast to blood pressure control, PCC administration was not associated with a reduced rate of hematoma enlargement in NOAC-related ICH. Our findings support the need of further investigations exploring new hemostatic reversal strategies for patients with factor Xa inhibitor-related ICH. Ann Neurol 2018;83:186-196.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25134DOI Listing
January 2018