RESUMO
BACKGROUND: Clinical observations indicated that vaccine-induced immune thrombosis with thrombocytopenia (VITT)-associated cerebral venous sinus thrombosis (CVST) often has a space-occupying effect and thus necessitates decompressive surgery (DS). While comparing with non-VITT CVST, this study explored whether VITT-associated CVST exhibits a more fulminant clinical course, different perioperative and intensive care unit management, and worse long-term outcome. METHODS: This multicenter, retrospective cohort study collected patient data from 12 tertiary centers to address priorly formulated hypotheses concerning the clinical course, the perioperative management with related complications, extracerebral complications, and the functional outcome (modified Rankin Scale) in patients with VITT-associated and non-VITT CVST, both with DS. RESULTS: Both groups, each with 16 patients, were balanced regarding demographics, kind of clinical symptoms, and radiological findings at hospital admission. Severity of neurological symptoms, assessed with the National Institute of Health Stroke Scale, was similar between groups at admission and before surgery, whereas more patients with VITT-associated CVST showed a relevant midline shift (≥ 4 mm) before surgery (100% vs. 68.8%, p = 0.043). Patients with VITT-associated CVST tended to undergo DS early, i.e., ≤ 24 h after hospital admission (p = 0.077). Patients with VITT-associated CVST more frequently received platelet transfusion, tranexamic acid, and fibrinogen perioperatively. The postoperative management was comparable, and complications were evenly distributed. More patients with VITT-associated CVST achieved a favorable outcome (modified Rankin Scale ≤ 3) at 3 months (p = 0.043). CONCLUSIONS: Although the prediction of individual courses remains challenging, DS should be considered early in VITT-associated CVST because an overall favorable outcome appears achievable in these patients.
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Trombose dos Seios Intracranianos , Trombocitopenia , Trombose , Humanos , Estudos Retrospectivos , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/cirurgia , Trombose/complicações , Trombocitopenia/induzido quimicamente , Progressão da DoençaRESUMO
OBJECTIVE: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. METHODS: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. RESULTS: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). CONCLUSIONS: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
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COVID-19 , Trombose Intracraniana , Trombose Venosa , Adenoviridae , Anticoagulantes/uso terapêutico , Vacinas contra COVID-19/efeitos adversos , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , SARS-CoV-2 , Vacinação/efeitos adversos , Trombose Venosa/complicaçõesRESUMO
BACKGROUND: Persisting coma is a common complication in (neuro)intensive care in neurological disease such as acute ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage. Amantadine acts as a nicotinic receptor antagonist, dopamine receptor agonist and non-competitive N-Methyl-D-aspartate receptor antagonist. Amantadine is a long-known drug, originally approved for treatment of influenza A and Parkinson`s Disease. It has been proven effective in improving vigilance after traumatic brain injury. The underlying mechanisms remain largely unknown, albeit anti-glutamatergic and dopaminergic effects might be most relevant. With limited evidence of amantadine efficacy in non-traumatic pathologies, the aim of our study is to assess the effects of amantadine for neuroenhancement in non-traumatic neurointensive patients with persisting coma. METHODS: An investigator-initiated, monocenter, phase IIb proof of concept open-label pilot study will be carried out. Based on the Simon design, 43 adult (neuro)intensive care patients who meet the clinical criteria of persisting coma not otherwise explained and < 8 points on the Glasgow Coma Scale (GCS) will be recruited. Amantadine will be administered intravenously for five days at a dosage of 100 mg bid. The primary endpoint is an improvement of at least 3 points on the GCS. If participants present as non-responders (increase < 3 points or decrease on the GCS) within the first 48 h, the dosage will be doubled from day three to five. Secondary objectives aim to demonstrate that amantadine improves vigilance via alternative scales. Furthermore, the incidence of adverse events will be investigated and electroencephalography (EEG) will be recorded at baseline and end of treatment. DISCUSSION: The results of our study will help to systematically assess the clinical utility of amantadine for treatment of persisting coma in non-traumatic brain injury. We expect that, in the face of only moderate treatment risk, a relevant number of patients will benefit from amantadine medication by improved vigilance (GCS increase of at least 3 points) finally leading to a better rehabilitation potential and improved functional neurological outcome. Further, the EEG data will allow evaluation of brain network states in relation to vigilance and potentially outcome prediction in this study cohort. TRIAL REGISTRATION: NCT05479032.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , AVC Isquêmico , Adulto , Humanos , Amantadina/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Coma , Projetos Piloto , Estudos Prospectivos , Estudo de Prova de ConceitoRESUMO
BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
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Vacinas contra COVID-19 , COVID-19 , Trombose Intracraniana , Trombocitopenia , Trombose , Vacinas , Trombose Venosa , Adulto , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Hemorragia Cerebral , Feminino , Humanos , Trombose Intracraniana/diagnóstico , Masculino , Fatores de Risco , SARS-CoV-2RESUMO
BACKGROUND AND PURPOSE: Reperfusion treatment in patients presenting with large vessel occlusion (LVO) and minor neurological deficits is still a matter of debate. We aimed to compare minor stroke patients treated with endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) or IVT alone. METHODS: Patients enrolled in the German Stroke Registry-Endovascular Treatment (GSR-ET) and the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) between June 2015 and December 2019 were analyzed. Minor stroke was defined as National Institutes of Health Stroke Scale (NIHSS) score ≤5, and LVO as occlusion of the internal carotid, carotid-T, middle cerebral, basilar, vertebral or posterior cerebral arteries. GSR-ET and SITS-ISTR IVT-treated patients were matched in a 1:1 ratio using propensity-score (PS) matching. The primary outcome was good functional outcome at 3 months (modified Rankin Scale score 0-2). RESULTS: A total of 272 GSR-ET patients treated with EVT and IVT (age 68.6 ± 14.0 years, 43.4% female, NIHSS score 4 [interquartile range 2-5]) were compared to 272 IVT-treated SITS-ISTR patients (age 69.4 ± 13.7, 43.4% female, NIHSS score 4 [2-5]). Good functional outcome was seen in 77.0% versus 82.9% (p = 0.119), mortality in 5.9% versus 7.9% (p = 0.413), and intracranial hemorrhage in 8.8% versus 12.5% (p = 0.308) of patients in the GSR-ET versus the SITS-ISTR IVT group, respectively. In a second PS-matched analysis, 624 GSR-ET patients (IVT rate 56.7%) and 624 SITS-ISTR patients (IVT rate 100%), good outcome was more often observed in the SITS-ISTR patients (68.2% vs. 80.9%; p < 0.001), and IVT independently predicted good outcome (odds ratio 2.16, 95% confidence interval 1.43-3.28). CONCLUSIONS: Our study suggests similar effectiveness of IVT alone compared to EVT with or without IVT in minor stroke patients. There is an urgent need for randomized controlled trials on this topic.
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Isquemia Encefálica , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/tratamento farmacológico , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Hemorragias Intracranianas , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Trombectomia , Terapia Trombolítica , Resultado do TratamentoRESUMO
BACKGROUND: The objective of the STREAM Trial was to evaluate the effect of simulation training on process times in acute stroke care. METHODS: The multicenter prospective interventional STREAM Trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre- and post-interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct-to-center patients receiving intravenous thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke-specific in situ simulation training. Primary outcome measure was the 'door-to-needle' time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the pre-existing treatment algorithm. RESULTS: The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre-intervention (interquartile range [IQR] 25-43 min) to 33 min (IQR 23-39 min, p = 0.03) post-intervention achieved by simulation-experienced stroke teams. Concerning EVT, we found significantly shorter door-to-groin times in patients who were treated by teams with simulation experience as compared to simulation-naive teams in the post-interventional phase (-21 min, simulation-naive: 95 min, IQR 69-111 vs. simulation-experienced: 74 min, IQR 51-92, p = 0.04). CONCLUSION: An intervention combining workflow refinement and simulation-based stroke team training has the potential to improve process times in acute stroke care.
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Treinamento por Simulação , Acidente Vascular Cerebral , Fibrinolíticos/uso terapêutico , Humanos , Estudos Prospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Tempo para o Tratamento , Resultado do TratamentoRESUMO
PURPOSE: Patients with Moyamoya Angiopathy (MMA) require hemodynamic evaluation to assess the risk of stroke. Assessment of cerebral blood flow with [15O]water PET and acetazolamide challenge is the diagnostic standard for the evaluation of the cerebral perfusion reserve (CPR). Estimation of the cerebrovascular reactivity (CVR) by use of breath-hold-triggered fMRI (bh-fMRI) as an index of CPR has been proposed as a reliable and more readily available approach. Recent findings suggest the use of resting-state fMRI (rs-fMRI) which requires minimum patient compliance. The aim of this study was to compare rs-fMRI to bh-fMRI and [15O]water PET in patients with MMA. METHODS: Patients with MMA underwent rs-fMRI and bh-fMRI in the same MRI session. Maps of the CVR gained by both modalities were compared retrospectively by calculating the correlation between the mean CVR of 12 volumes of interest. Additionally, the rs-maps of a subgroup of patients were compared to CPR-maps gained by [15O]water PET. RESULTS: The comparison of the rs-maps and the bh-maps of 24 patients revealed a good correlation (Pearson's r = 0.71 ± 0.13; preoperative patients: Pearson's r = 0.71 ± 0.17; postoperative patients: Pearson's r = 0.71 ± 0.11). The comparison of 7 rs-fMRI data sets to the corresponding [15O]water PET data sets also revealed a high level of agreement (Pearson's r = 0.80 ± 0.19). CONCLUSION: The present analysis indicates that rs-fMRI might be a promising non-invasive method with almost no patient cooperation needed to evaluate the CVR. Further prospective studies are required.
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Imageamento por Ressonância Magnética , Doença de Moyamoya , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Hemodinâmica , Humanos , Imageamento por Ressonância Magnética/métodos , Doença de Moyamoya/diagnóstico por imagem , Estudos Retrospectivos , ÁguaRESUMO
PURPOSE: Scarce evidence exists regarding end-of-life decision (EOLD) in neurocritically ill patients. We investigated the factors associated with EOLD making, including the group and individual characteristics of involved healthcare professionals, in a multiprofessional neurointensive care unit (NICU) setting. MATERIALS AND METHODS: A prospective, observational pilot study was conducted between 2013 and 2014 in a 10-bed NICU. Factors associated with EOLD in long-term neurocritically ill patients were evaluated using an anonymised survey based on a standardised questionnaire. RESULTS: 8 (25%) physicians and 24 (75%) nurses participated in the study by providing their 'treatment decisions' for 14 patients at several time points. EOLD was 'made' 44 (31%) times, while maintenance of life support 98 (69%) times. EOLD patterns were not significantly different between professional groups. The individual characteristics of the professionals (age, gender, religion, personal experience with death of family member and NICU experience) had no significant impact on decisions to forgo or maintain life-sustaining therapy. EOLD was patient-specific (intraclass correlation coefficient: 0.861), with the presence of acute life-threatening disease (OR (95% CI): 18.199 (1.721 to 192.405), p=0.038) and low expected patient quality of life (OR (95% CI): 9.276 (1.131 to 76.099), p=0.016) being significant and independent determinants for withholding or withdrawing life-sustaining treatment. CONCLUSIONS: Our findings suggest that EOLD in NICU relies mainly on patient prognosis and not on the characteristics of the healthcare professionals.
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Qualidade de Vida , Assistência Terminal , Tomada de Decisões , Humanos , Cuidados para Prolongar a Vida , Projetos Piloto , Estudos Prospectivos , Suspensão de TratamentoRESUMO
BACKGROUND AND PURPOSE: Poststroke delirium (PSD) is an independent predictor of unfavorable outcome. Despite its individual and socioeconomic burden, its frequency, clinical course, and routine detection remain unresolved. This study aimed to assess psychometric properties of established delirium screening tools and investigate the natural course of PSD. METHODS: This study investigated patients presenting with high-risk transient ischemic attacks or ischemic stroke within 24 hours during a 3-month period. Twice-daily screenings for PSD were done using the confusion assessment method, nursing delirium scale, and rapid delirium assessment, and evaluated for noninferiority against Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. We investigated demographic and stroke characteristics as predictors of PSD, neurological deficits as predictors of false screening results, and conducted a simulation study to estimate the best timing to identify PSD. RESULTS: We enrolled 141 patients (73.8±10.4 years of age, 61 female) with a mean National Institutes of Health Stroke Scale score of 6.4±6.5. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based PSD incidence was 39%, which manifested within 24 hours in 25% and 72 hours in almost all cases. The confusion assessment method was the only screening tool noninferior to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ratings providing a sensitivity of 82% and specificity of 80%. Age (odds ratio, 1.07 [1.02-1.13] per year, P=0.004) and National Institutes of Health Stroke Scale (odds ratio, 1.24 [1.15-1.34] per point, P<0.001) were predictors of PSD. False-positive screening results were associated with stroke-induced disorientation (odds ratio, 6.1 [3.2-11.61], P<0.001) and neglect (odds ratio, 2.17 [1.22-3.87], P=0.008). Simulations revealed that one in 4 cases is missed with less than daily screenings. CONCLUSIONS: PSD is a common complication of stroke and transient ischemic attack. Detection is challenged by confounding effects such as focal neurological deficits and the necessity for at least daily screenings. Future studies are required to investigate implementation of these findings in clinical routine. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03930719.
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Delírio/diagnóstico , Delírio/etiologia , Testes Neuropsicológicos , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Delírio/epidemiologia , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND AND PURPOSE: Poststroke delirium (PSD) comprises a common and severe complication after stroke. However, treatment options for PSD remain insufficient. We investigated whether prophylactic melatonin supplementation may be associated with reduced risk for PSD. METHODS: Consecutive patients admitted to the Tübingen University Stroke Unit, Tübingen, Germany, with acute ischemic stroke (AIS), who underwent standard care between August 2017 and December 2017, and patients who additionally received prophylactic melatonin (2 mg per day at night) within 24 h of symptom onset between August 2018 and December 2018 were included. Primary outcomes were (i) PSD prevalence in AIS patients and (ii) PSD risk and PSD-free survival in patients with cerebral infarction who underwent melatonin supplementation compared to propensity score-matched (PSM) controls. Secondary outcomes included time of PSD onset and PSD duration. RESULTS: Out of 465 (81.2%) patients with cerebral infarction and 108 (18.8%) transient ischemic attack (TIA) patients, 152 (26.5%) developed PSD (median time to onset [IQR]: 16 [8-32] h; duration 24 [8-40] h). Higher age, cerebral infarction rather than TIA, and higher National Institutes of Health Stroke Scale score and aphasia on admission were significant predictors of PSD. After PSM (164 melatonin-treated patients with cerebral infarction versus 164 matched controls), 42 (25.6%) melatonin-treated patients developed PSD versus 60 (36.6%) controls (odds ratio, 0.597; 95% confidence interval, 0.372-0.958; p = 0.032). PSD-free survival differed significantly between groups (p = 0.027), favoring melatonin-treated patients. In patients with PSD, no between-group differences in the time of PSD onset and PSD duration were noted. CONCLUSIONS: Patients prophylactically treated with melatonin within 24 h of AIS onset had lower risk for PSD than patients undergoing standard care. Prospective randomized trials are warranted to corroborate these findings.
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Isquemia Encefálica , Delírio , AVC Isquêmico , Melatonina , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Humanos , Pontuação de Propensão , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
OBJECTIVES: To investigate the hemostatic efficacy of combined desmopressin (1-deamino-8-D-arginine vasopressin) and platelet transfusion in reducing hematoma expansion in acute, spontaneous intracerebral hemorrhage under antiplatelet treatment. DESIGN: Single-center, nonrandomized study, performed between 2006 and 2014. SETTING: Tertiary University Hospital of Tuebingen, Germany. PATIENTS: Adult patients with intracerebral hemorrhage under antiplatelet treatment and follow-up CT at 24 ± 12 hours were included. Exclusion criteria included other intracerebral hemorrhage causes, anticoagulation, coagulopathy, or immediate surgery after baseline-CT. INTERVENTIONS: Treatment with IV 1-deamino-8-D-arginine vasopressin (0.4 µg/kg) + platelet transfusion (2 U) within 60 minutes of intracerebral hemorrhage under antiplatelet treatment diagnosis on brain imaging. MEASUREMENTS AND MAIN RESULTS: Primary outcome was relative hematoma expansion from baseline to follow-up CT. Secondary outcomes included secondary intraventricular hemorrhage or hydrocephalus upon follow-up CT, thromboembolic events before discharge, and the 3-month functional outcome (assessed by modified Rankin Scale). One-hundred forty patients were included, 72 treated versus 68 controls. Times of symptom-onset-to-baseline-CT (hr) (median [interquartile range]: 3 [4] vs 5 [5]; p = 0.468) and follow-up CT (26 [18] vs 19 [12]; p = 0.352) were similar between groups. No between-group differences of total intracerebral hematoma expansion (%) (median [interquartile range]: 8.5 [12.4] vs 9.1 [16.5]; p = 0.825), intraparenchymal (10.7 [23.1] vs 9.2 [20.7]; p = 0.900), and intraventricular hematoma expansion (14.5 [63.2] vs 6.1 [40.4]; p = 0.304) were noted. Among patients with hematoma expansion greater than or equal to 33% compared with baseline, 16 (52%) received treatment versus 15 (48%) controls. The occurrence of hematoma expansion greater than or equal to 33% was similar between groups (p = 0.981). Rates of secondary intraventricular hemorrhage, hydrocephalus, and thromboembolic events were similar between groups. Treatment with 1-deamino-8-D-arginine vasopressin + platelet transfusion was not associated with the 3-month functional outcome (adjusted odds ratio, 1.570; 95% CI, 0.721-3.419; p = 0.309). CONCLUSIONS: In line with the randomized Platelet Transfusion Versus Standard Care After Acute Stroke Due to Spontaneous Cerebral Hemorrhage Associated With Antiplatelet Therapy trial, our results suggest no hemostatic efficacy of early platelet transfusion in intracerebral hemorrhage under antiplatelet treatment. Contrary to results of preclinical and clinical nonintracerebral hemorrhage studies, adjunct 1-deamino-8-D-arginine vasopressin showed no benefit in limiting hematoma expansion or improving functional outcome.
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Hemorragia Cerebral/induzido quimicamente , Desamino Arginina Vasopressina/uso terapêutico , Hematoma/terapia , Hemostáticos/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Transfusão de Plaquetas , Idoso , Encéfalo/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Terapia Combinada , Desamino Arginina Vasopressina/administração & dosagem , Feminino , Hemostáticos/administração & dosagem , Humanos , Masculino , Neuroimagem , Inibidores da Agregação Plaquetária/uso terapêutico , Transfusão de Plaquetas/métodos , Tomografia Computadorizada por Raios XRESUMO
Edoxaban, alongside other direct oral anticoagulants (DOAC), is increasingly used for prevention of thromboembolism, including stroke. Despite DOAC therapy, however, annual stroke rate in patients with atrial fibrillation remains 1-2%. Rapid exclusion of relevant anticoagulation is necessary to guide thrombolysis or reversal therapy but, so far, no data exists on the effect of edoxaban on available point-of-care test systems (POCT). To complete our previous investigation on global coagulation-POCT for the detection of DOAC, we evaluated whether CoaguChek®-INR (CC-INR) is capable of safely ruling out edoxaban concentrations above the current treatment thresholds of 30/50 ng/mL in a blood sample. We studied patients receiving a first dose of edoxaban; excluding subjects receiving other anticoagulants. Six blood samples were collected from each patient: before drug intake, 0.5, 1, 2 and 8 h after intake, and at trough (24 h). CC-INR and mass spectrometry for edoxaban concentrations were performed for each time-point. One hundred and twenty blood samples from 20 patients contained 0-302 ng/mL of edoxaban. CC-INR ranged from 0.9 to 2.3. Pearson's correlation coefficient showed strong correlation between CC-INR and edoxaban concentrations (r = 0.73, p < 0.001). Edoxaban concentrations > 30 and > 50 ng/mL were ruled out by CC-INR ≤ 1.0 and ≤ 1.1, respectively, with high specificity (> 95%), and a sensitivity of 44% (95%-confidence interval: 30-59%) and 86% (74-93%), respectively. Our study represents the first evaluation of coagulation-POCT in edoxaban-treated patients. CC-POCT is suitable to safely exclude clinically relevant edoxaban concentrations prior to thrombolysis, or guide reversal therapy in stroke patients.
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Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/uso terapêutico , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Idoso , Fibrilação Atrial/tratamento farmacológico , Testes de Coagulação Sanguínea , Monitoramento de Medicamentos , Inibidores do Fator Xa/sangue , Inibidores do Fator Xa/farmacologia , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Estudos Prospectivos , Piridinas/sangue , Piridinas/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Tiazóis/sangue , Tiazóis/farmacologiaAssuntos
COVID-19/prevenção & controle , ChAdOx1 nCoV-19/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Púrpura Trombocitopênica Idiopática/etiologia , Púrpura Trombocitopênica Idiopática/terapia , Adulto , Estudos de Coortes , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Adulto JovemRESUMO
INTRODUCTION: Hepatitis E virus (HEV) is endemic in Asian and African countries but is rarely reported in Western countries. Although there are some prominent neurological manifestations, HEV is rarely recognized by neurologists. METHODS: This is a case report of myositis induced by HEV. RESULTS: We report the life-threatening case of a 57-year-old man with flaccid tetraparesis due to myositis, acute hepatitis, and renal failure caused by HEV infection. Muscle biopsy revealed scattered myofiber necrosis with a diffuse, mild lymphomonocytic infiltrate in the endomysium and perimysium. Because the patient suffered from an acute HEV infection with a rapidly progressive course of severe myopathy, we started ribavirin treatment. He recovered partially within 3 weeks and recovered fully within 6 months. CONCLUSION: This case highlights a neurological manifestation of endemic HEV infection with severe myositis in a patient with alcoholic chronic liver disease. Ribavirin treatment is effective in severe HEV infection and may also lead to rapid neurological recovery.
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Hepatite E/complicações , Miosite/etiologia , Miosite/virologia , Eletromiografia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Miosite/diagnósticoRESUMO
BACKGROUND: Anti-NMDA receptor encephalitis typically manifests as severe multistage neuropsychiatric syndrome. However, milder or incomplete forms of the disorder have been recognised. Here, we report on a patient with anti-NMDA receptor encephalitis with a clinical phenotype mimicking the syndrome of headache with neurological deficits and cerebrospinal fluid (CSF) lymphocytosis (HaNDL). CASE: A 67-year-old man presented with recurrent stereotyped episodes of hemianopia, aphasia and right hemiparesis accompanied by throbbing headaches as well as confusion and agitation. CSF analysis showed lymphocytic pleocytosis. Additional analysis revealed NMDA receptor IgG antibodies in the patient's CSF. Following immunotherapy, no further episodes occurred and NMDAR antibodies became undetectable. No NMDAR or other neuronal antibodies were detected in archived serum and CSF samples of 12 HaNDL patients fulfilling the current diagnostic criteria. CONCLUSIONS: While anti-NMDAR encephalitis can manifest with a HaNDL-like clinical picture, HaNDL syndrome itself does not appear to be mediated by anti-NMDAR antibodies.
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Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Diagnóstico Diferencial , Transtornos da Cefaleia/diagnóstico , Idoso , Humanos , Linfocitose/líquido cefalorraquidiano , Linfocitose/diagnóstico , MasculinoRESUMO
RATIONALE AND OBJECTIVES: Fluid-attenuated inversion recovery (FLAIR) imaging is playing an increasingly significant role in the detection of brain metastases with a concomitant increase in the number of magnetic resonance imaging (MRI) examinations. Therefore, the purpose of this study was to investigate the impact on image quality and diagnostic confidence of an innovative deep learning-based accelerated FLAIR (FLAIRDLR) sequence of the brain compared to conventional (standard) FLAIR (FLAIRS) imaging. MATERIALS AND METHODS: Seventy consecutive patients with staging cerebral MRIs were retrospectively enrolled in this single-center study. The FLAIRDLR was conducted using the same MRI acquisition parameters as the FLAIRS sequence, except for a higher acceleration factor for parallel imaging (from 2 to 4), which resulted in a shorter acquisition time of 1:39 minute instead of 2:40 minutes (-38%). Two specialized neuroradiologists evaluated the imaging datasets using a Likert scale that ranged from 1 to 4, with 4 indicating the best score for the following parameters: sharpness, lesion demarcation, artifacts, overall image quality, and diagnostic confidence. Additionally, the image preference of the readers and the interreader agreement were assessed. RESULTS: The average age of the patients was 63 ± 11years. FLAIRDLR exhibited significantly less image noise than FLAIRS, with P-values of< .001 and< .05, respectively. The sharpness of the images and the ability to detect lesions were rated higher in FLAIRDLR, with a median score of 4 compared to a median score of 3 in FLAIRS (P-values of<.001 for both readers). In terms of overall image quality, FLAIRDLR was rated superior to FLAIRS, with a median score of 4 vs 3 (P-values of<.001 for both readers). Both readers preferred FLAIRDLR in 68/70 cases. CONCLUSION: The feasibility of deep learning FLAIR brain imaging was shown with additional 38% reduction in examination time compared to standard FLAIR imaging. Furthermore, this technique has shown improvement in image quality, noise reduction, and lesion demarcation.
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Neoplasias Encefálicas , Aprendizado Profundo , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Encefálicas/patologia , ArtefatosRESUMO
Importance: Elevated values of high-sensitivity cardiac troponin (hs-cTn) are common in patients with acute ischemic stroke and are associated with poor prognosis. However, diagnostic and therapeutic implications in patients with ischemic stroke remain unclear. Objective: To identify factors indicative of myocardial infarction (MI) in patients with acute ischemic stroke and hs-cTn elevation. The primary hypothesis was that a dynamic change of hs-cTn values (>50% change) in patients with acute ischemic stroke indicates MI. Design, Setting, and Participants: This cross-sectional study was a prospective, observational study with blinded end-point assessment conducted across 26 sites in Germany. Patients were included if they had acute ischemic stroke within 72 hours and either (1) highly elevated hs-cTn values on admission (>52 ng/L) or (2) hs-cTn levels above the upper limit of normal and a greater than 20% change at repeated measurements. Patients were enrolled between August 2018 and October 2020 and had 1 year of follow-up. Statistical analysis was performed between April 2022 and August 2023. Exposure: Standardized electrocardiography, echocardiography, and coronary angiography. Main Outcome and Measures: Diagnosis of MI as adjudicated by an independent end-point committee based on the findings of electrocardiography, echocardiography, and coronary angiography. Results: In total, 254 patients were included. End points were adjudicated in 247 patients (median [IQR] age, 75 [66-82] years; 117 were female [47%] and 130 male [53%]). MI was present in 126 of 247 patients (51%) and classified as type 1 MI in 50 patients (20%). Dynamic change in hs-cTn value was not associated with MI in univariable (32% vs 38%; χ2 P = .30) or adjusted comparison (odds ratio, 1.05; 95% CI, 0.31-3.33). The baseline absolute hs-cTn value was independently associated with type 1 MI. The best cutoffs for predicting type 1 MI were at hs-cTn values 5 to 10 times the upper limit normal. Conclusions and Relevance: This study found that in patients with acute ischemic stroke, a dynamic change in hs-cTn values did not identify MI, underscoring that dynamic changes do not identify the underlying pathophysiological mechanism. In exploratory analyses, very high absolute hs-cTn values were associated with a diagnosis of type 1 MI. Further studies are needed how to best identify patients with stroke who should undergo coronary angiography.
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AVC Isquêmico , Infarto do Miocárdio , Humanos , Masculino , Feminino , Idoso , AVC Isquêmico/sangue , AVC Isquêmico/complicações , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/sangue , Estudos Transversais , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos Prospectivos , Eletrocardiografia , EcocardiografiaRESUMO
BACKGROUND: Relapses in multiple sclerosis (MS) patients are usually defined as subacute clinical symptoms that last for at least 24 h. To validate a clinical relapse on magnetic resonance imaging (MRI), an anatomically fitting lesion with gadolinium enhancement in the central nervous system (CNS) would be mandatory. The aim of this study was to validate clinical relapses in regard to the concomitant detection of active, anatomically fitting MRI lesions. METHODS: We performed a retrospective analysis of 199 MS patients with acute relapse who had received an MRI scan before the initiation of methylprednisolone (MPS) therapy. Clinical data and MRIs were systematically reanalyzed by correlating clinical symptoms with their anatomical representation in the CNS. Patients were then categorized into subgroups with a clinical-radiological match (group 1) or clinical-radiological mismatch (group 2) between symptoms and active, topographically fitting lesions and further analyzed in regard to clinical characteristics. RESULTS: In 43% of our patients, we observed a clinical-radiological mismatch (group 2). Further analysis of patient characteristics showed that these patients were significantly older at the time of relapse. MS patients in group 2 also showed a significantly longer disease duration and significantly more previous relapses when compared to group 1. Comparing symptom clusters, the appearance of motor dysfunction during the current relapse was significantly more frequent in group 2 than in group 1. The overall dose of MPS treatment was significantly lower in group 2 than in group 1 with a similar treatment response in both groups. CONCLUSIONS: The substantial clinical-radiological mismatch during acute relapse in our study could be explained by several factors, including a psychosomatic component or disturbance of network connectivity. Alternatively, secondary progression or a diffuse neuro-inflammatory process might cause clinical symptoms, especially in older patients with a longer disease duration. As a consequence, treatment of clinical relapses and the definition of breakthrough disease should be reconsidered in regard to combined clinical and MRI criteria and/or additional biomarkers. Further studies are necessary to address the contribution of diffuse neuro-inflammation to the clinical presentation of symptoms.
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OBJECTIVE: Post-stroke delirium (PSD) is a frequent and with regard to outcome unfavorable complication in acute stroke. The neurobiological mechanisms predisposing to PSD remain poorly understood, and biomarkers predicting its risk have not been established. We tested the hypothesis that hypoexcitable or disconnected brain networks predispose to PSD by measuring brain reactivity to transcranial magnetic stimulation with electroencephalography (TMS-EEG). METHODS: We conducted a cross-sectional study in 33 acute stroke patients within 48 hours of stroke onset. Brain reactivity to single-pulse TMS of dorsolateral prefrontal cortex, primary motor cortex and superior parietal lobule of the right hemisphere was quantified by response intensity, effective connectivity, perturbational complexity index (PCIST), and natural frequency of the TMS-EEG response. PSD development was clinically tracked every 8 hours before and for 7 days following TMS-EEG. RESULTS: Fourteen patients developed PSD while 19 patients did not. The PSD group showed lower excitability, effective connectivity, PCIST and natural frequency compared to the non-PSD group. The maximum PCIST over all three TMS sites demonstrated largest classification accuracy with a ROC-AUC of 0.943. This effect was independent of lesion size, affected hemisphere and stroke severity. Maximum PCIST and maximum natural frequency correlated inversely with delirium duration. CONCLUSIONS: Brain reactivity to TMS-EEG can unravel brain network states of reduced excitability, effective connectivity, perturbational complexity and natural frequency that identify acute stroke patients at high risk for development of delirium. SIGNIFICANCE: Findings provide novel insight into the pathophysiology of pre-delirium brain states and may promote effective delirium prevention strategies in those patients at high risk.
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Córtex Cerebral , Delírio , Eletroencefalografia , Acidente Vascular Cerebral , Estimulação Magnética Transcraniana , Humanos , Estudos Transversais , Delírio/etiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Córtex Cerebral/fisiopatologia , RiscoRESUMO
Background and aims: Intravenous thrombolysis (IVT) is standard of care for disabling acute ischemic stroke (AIS) within a time window of ⩽ 4.5 h. Some AIS patients cannot be treated with IVT due to limiting contraindications, including heparin usage in an anticoagulating dose within the past 24 h or an elevated activated prothrombin time (aPTT) > 15 s. Protamine is a potent antidote to unfractionated heparin. Objectives: The objective of this study was to investigate the safety and efficacy of IVT in AIS patients after antagonization of unfractionated heparin with protamine. Methods: Patients from our stroke center (between January 2015 and September 2021) treated with IVT after heparin antagonization with protamine were analyzed. National Institutes of Health Stroke Scale (NIHSS) was used for stroke severity and modified Rankin Scale (mRS) for outcome assessment. Substantial neurological improvement was defined as the difference between admission and discharge NIHSS of ⩾8 or discharge NIHSS of ⩽1. Good outcome at follow-up after 3 months was defined as mRS 0-2. Safety data were obtained for mortality, symptomatic intracerebral hemorrhage (sICH), and for adverse events due to protamine. Second, a systematic review was performed searching PubMed and Scopus for studies and case reviews presenting AIS patients treated with IVT after heparin antagonization with protamine. The search was limited from January 1, 2011 to September 29, 2021. Furthermore, we conducted a propensity score matching comparing protamine-treated patients to a control IVT group without protamine (ratio 2:1, match tolerance 0.2). Results: A total of 16 patients, 5 treated in our hospital and 11 from literature, [65.2 ± 13.1 years, 37.5% female, median premorbid mRS (pmRS) 1 (IQR 1, 4)] treated with IVT after heparin antagonization using protamine were included and compared to 31 IVT patients [76.2 ± 10.9 years, 45% female, median pmRS 1 (IQR 0, 2)]. Substantial neurological improvement was evident in 68.8% of protamine-treated patients versus 38.7% of control patients (p = 0.028). Good clinical outcome at follow-up was observed in 56.3% versus 58.1% of patients (p = 0.576). No adverse events due to protamine were reported, one patient suffered sICH after secondary endovascular thrombectomy of large vessel occlusion. Mortality was 6.3% versus 22.6% (p = 0.236). Conclusion: IVT after heparin antagonization with protamine seems to be safe and, prospectively, may extend the number of AIS patients who can benefit from reperfusion treatment using IVT. Further prospective registry trials would be helpful to further investigate the clinical applicability of heparin antagonization.